id000006 10.3205/id000006 urn:nbn:de:0183-id0000064 Review Article Hof Hof Herbert H Prof. Dr. med.

Labor Limbach, Im Breitspiel 15, 69126 Heidelberg, Germany, Phone: +49 6221 34 32 342, Fax: +49 6221 34 32 220Labor Limbach, Heidelberg, Germany

herbert.hof@labor-limbach.de author German Medical Science GMS Publishing House

Düsseldorf

610 Listeria antibiotics in vitro activities intracellular action animal experiments clinical activities 20131010 engl 2195-8831 1 GMS Infectious Diseases GMS Infect Dis 06 The combination of amoxicillin or ampicillin, respectively, with an aminoglycoside remains still the standard therapy of infections with Listeria monocytogenes, although it has been questioned in clinical studies as well as in animal experiments whether the addition of an aminoglycoside really improves the outcome. There are some alternatives for example cotrimoxazole. Several microbiological and experimental evidences vote for the use of quinolones, in particular of moxifloxacin, against these facultative intracellular bacteria; clinical experiences with these agents are, however, limited. In addition to these drugs a large number of antimicrobials can be used for therapy of listeriosis in certain situations. Cephalosporins should be avoided. Resistance development is not a major problem. Microbiology of Listeria spp.The genus Listeria comprises of at least 10 different species , , , . Most of these are, however, non-pathogenic bacteria; yet they have to be differentiated from each other when Listeriae are isolated from the environment for example from various food items. In human cases of listeriosis almost exclusively Listeria monocytogenes is found. The individual isolates of this major pathogen can differ in their virulence as well as in their antigenic surface composition. Serovars 1 and 4 represent by far the most frequent variants. A striking difference between non-pathogenic and pathogenic strains is the presence of a series of virulence factors most of which are located in a pathogenicity island on the chromosome encoding a haemolysin (listeriolysin), phospholipases and an actin polymerizing protein .In principle, Listeriae are geophilic, i.e. they reside in the soil, since they are non-fastidious. They are able to adapt to various challenges by multiple changes in bacterial metabolism and gene expression and therefore can grow at many quite different sites; hence, vegetables are contaminated and even milk and meat and fish products can get polluted secondarily. This means that various food items, especially soft-cheese, salami, graved salmon, ready-to-eat food and salads, are the source of infections of men and animals . Pathogenesis: Intracellular growth is a relevant processWhereas the exposition to Listeriae via various food items is rather frequent, listeriosis is rare. One reason is, that the innate immune system generally protects the hosts to some extent. For example there are some antimicrobial peptides, such as defensins. In principle L. monocytogenes is susceptible to a large range of human as well as non-human antimicrobial peptides , . It can be anticipated that these natural products might reduce the bacterial load of the ingested food. Hence, the chance for pathogenic bacteria to come into contact with the mucosal epithelium is lessened and the risk of infection is lowered.Surface proteins of L. monocytogenes such as Inl A und B, which are leucine-rich repeat-containing proteins, bind to special receptors on the host cell membrane and trigger the uptake of L. monocytogenes by clathrin-dependant mechanisms . Once inside a host cell, i.e. in a membrane bound vacuole, the bacterium is confronted to unfavorable growth conditions such as low pH, kationic antimicrobial compounds, cytokines and lytic enzymes .By means of several virulence factors, such as hemolysin (listeriolysin O) and phospholipases, the pathogenic bacteria produce a hole in the vacuolar membrane through which the bacteria may rapidly escape into the cytosol a privileged site, where the bacterium is largely protected against host’s defense mechanisms as well as most antibiotics. There, they are able to multiply. By means of a cell wall protein, i.e. Act A, they can actively polymerize actin filaments of the host cell just on one pole of the bacterial cell, so that the bacterium is pushed forward. By this type of intracellular motility they migrate through the host cell and by chance the bacteria may arrive at the inner front of the host cell membrane. This situation triggers the extrusion of long filaments of the host cell containing a bacterium, which penetrate into adjacent host cells and at last are integrated in this second host cell . By this way, L. monocytogenes is thought to be able to spread from one host cell to another without an extracellular stage and to cross anatomical barriers such as the intestinal mucosa, the blood-brain-barrier or the placenta . Indeed, during listeriosis the bacteria are found within the cytosol and even within the nucleus of various host cells for example in neurons .Within the host cells, several bacterial components are processed and typically presented together with MHC class I-receptors at the cell surface to CD8 T-lymphocytes . Indeed, the intracellular habitat of L. monocytogenes calls for a cell-mediated immune response, which is histologically characterized by a granulomatous inflammatory reaction developing after a few days of infection .On the other hand, L. monocytogenes is quite able to grow extracellularly, too. Like other pyogenic bacteria they induce an acute granulocytic inflammatory response; typically in the CSF in patients with Listeria meningitis the majority of visible bacteria are extracellular surrounded by polymorphonuclear granulocytes . Epidemiology of listeriosisExposure of humans to L. monocytogenes is quite frequent, but infections are rare. In most instances these infections occur sporadically, but sometimes small outbreaks have been reported. In some countries such as USA the incidence has decreased whereas in others such as England, Wales, the Netherlands and Germany, the incidence of listeriosis has grown up in the last few years . Food-borne infections with L. monocytogenes predominantly occur in immunocompromised patients. Less than 30% of infections develop in otherwise healthy subjects. Advanced age, acute myeloic leukemia as well as iatrogenic immunosuppression by steroids and lymphotoxic agents (mycophenolic acid, cyclosporine A, azathioprin, etanercept) in organtransplant recipients, in cancer patients, in individuals with severe rheumatic diseases and in auto-immune disorders are the most common predisposing factors. In recent times immunomodulating monoclonal antibodies directed against TNFα or Il 1 such as retuximab, infliximab or adalinumab are of special concern. In addition debilitating diseases such as HIV infection, diabetes and liver cirrhosis as well as conditions resulting in high iron load will facilitate the manifestation of listeriosis .In rare cases a contact of farmers and veterinaries with infected animals may lead to a direct inoculation of Listeriae into the skin or the conjunctival mucosa inducing localized infections. Furthermore, nosocomial infections, particularly of newborns, have been described . Clinical manifestationsWhereas intestinal symptoms of an infection with L. m</PlainText></TextGroup>onocytogenes such as enteritis are outlined by a few patients, in most instances the prominent clinical manifestations are sepsis, meningitis and encephalitis, sometimes in combinations. Obviously, L. monocytogenes is one of those bacterial pathogens able to cross first the intestinal mucosa and then the blood brain barrier and other anatomical structures. In only few instances other organs may be involved; endocarditis, arthritis, cholecystitis etc. have been reported. Overt disease develops primarily &#8211; but not exclusively &#8211; in immunocompromised adult patients especially in the very old. Pyogenic local infections of the skin and the conjunctival mucosa are rather uncommon <TextLink reference="20"></TextLink>.</Pgraph><Pgraph>A particular situation exists, when a pregnant women being about 12 times more prone to listeriosis than normal population will be infected; during a short episode of septic spreading of bacteria which will be anticipated as a flu-like disease a colonization of the placenta may happen, and in some cases a transition of bacteria through the anatomical barrier may result in an intrauterine infection of the fetus <TextLink reference="21"></TextLink>. While most pregnancy-related infections of the fetus occur during the third trimester, listeriosis can develop at any time during pregnancy and, in some instances, asymptomatic pregnant women may pass on infection to the fetus.</Pgraph></TextBlock> <TextBlock linked="yes" name="Diagnostics"> <MainHeadline>Diagnostics</MainHeadline><Pgraph>L. monocytogenes are non-fastidious and can easily be grown in various nutrient media. Since bacteremia is often only transient, blood cultures can, however, remain negative. Meningitis can be approved by microscopy and culture of CSF. During encephalitis, however, the bacteria may reside entrapped in infective foci and cannot be detected in CSF in every case. Consequently, in some cases Listeria infections are undiagnosed. In these cases, imaging methods such as CT scan <TextLink reference="22"></TextLink> can help to make a presumptive diagnosis. Pyogenic infections of other organs can be diagnosed by biopsies. </Pgraph></TextBlock> <TextBlock linked="yes" name="Therapy"> <MainHeadline>Therapy</MainHeadline><SubHeadline>Antibiotic activities against Listeria spp.</SubHeadline><SubHeadline2>Susceptibility of Listeria spp. in vitro</SubHeadline2><Pgraph>In case of testing susceptibility of L. monocytogenes special conditions and break-points have been proposed by CLSI for penicillin, ampicillin as well as cotrimoxazole <TextLink reference="23"></TextLink>. All other antibiotics are not recommended for routine testing, since generally, clinical isolates of L. monocytogenes are susceptible in vitro to a wide range of antibiotics except to older quinolones, cephalosporins, aztreonam and fosfomycin; it is noteworthy that only a narrow range of MICs is found <TextLink reference="7"></TextLink>, <TextLink reference="24"></TextLink> (Table 1 <ImgLink imgNo="1" imgType="table"/>). The susceptibility of clinical isolates can be predicted with a high probability even without a laboratory testing <TextLink reference="7"></TextLink>. In particular resistance to penicillins does not have any practical impact in medicine&#33; Conclusively, microbial resistance does not play a major role in the therapy of listeriosis <TextLink reference="25"></TextLink>. Amoxicillin is slightly more active than ampicillin against <TextGroup><PlainText>L. m</PlainText></TextGroup>onocytogenes, since the MIC values are marginally lower and the time to kill is somewhat lower.</Pgraph><Pgraph>Occasionally, resistance or at least reduced susceptibility to a few antibiotics, such as tetracyclines, aminoglycosides and chloramphenicol have been found in food isolates <TextLink reference="26"></TextLink>. Indeed, a horizontal transfer of antimicrobial resistance from other gram-positive bacteria to Listeria by means of conjugative genetic elements such as transposons and plasmids has been observed <TextLink reference="27"></TextLink>. The meaning of a report on penicillin resistance in all 9 Listeria isolates from chickens in East Africa <TextLink reference="28"></TextLink> remains unclear.</Pgraph><SubHeadline2>The role of Penicillin Binding Proteins</SubHeadline2><Pgraph>L. monocytogenes produces 5 vital penicillin binding proteins (PBP) <TextLink reference="29"></TextLink> as well as some additional PBP-like structures <TextLink reference="30"></TextLink>. About 80 up to 600 copies of each protein are present in one bacterial cells; it is obvious not necessary to neutralize absolutely all of these targets by penicillin molecules but only a majority of them. The activity of PBP3 is essential whereas neutralization of the other targets can be partially compensated.</Pgraph><Pgraph>Cephalosporins, in particular those of the 3<Superscript>rd</Superscript> generation, as well as mecillinam and aztreonam, have a rather low affinity for the PBP3. Hence, L. monocytogenes is generally resistant to these betalactam antibiotics except of a very few isolates <TextLink reference="31"></TextLink>. Penicillins, especially ampicillin and amoxicillin, are active as well as imipenem disposing even of lower MIC values than ampicillin <TextLink reference="32"></TextLink>.</Pgraph><Pgraph>The effect of betalactams is, however, only bacteriostatic in vitro for L. monocytogenes <TextLink reference="7"></TextLink>, <TextLink reference="32"></TextLink>, which is a definite disadvantage in a compromised patient. Only at rather high concentrations, i.e. 16 fold above the MIC, killing is achieved within 6 hours <TextLink reference="30"></TextLink>. On the other hand, the production of essential virulence factors such as hemolysin, is reduced already at low, subinhibitory concentrations <TextLink reference="33"></TextLink>.</Pgraph><SubHeadline2>Resistance mechanisms of Listeria spp. to quinolones</SubHeadline2><Pgraph>L. monocytogenes is inherently resistant to quinolones of the first generation such as nalidixc acid <TextLink reference="34"></TextLink>, most probably due to an inherited mutation in the active center of subunit A of the DNA gyrase <TextLink reference="35"></TextLink>. At positions 88 and 84 two amino acids, namely Phe and Tyr, are found in <TextGroup><PlainText>L. m</PlainText></TextGroup>onocytogenes instead of Asp&#47;Glu and Ser residues in quinolone susceptible bacteria. Newer quinolones such as norfloxacin, ciprofloxacin <TextLink reference="34"></TextLink>, ofloxacin <TextLink reference="36"></TextLink> and clinafloxacin <TextLink reference="37"></TextLink>, however, are rather active exerting a rapid and strong concentration dependant bactericidal effect. Especially moxifloxacin exerts excellent concentration-dependent bactericidal activities against a lot of different strains of <TextGroup><PlainText>L. m</PlainText></TextGroup>onocytogenes exceeding definitely that of ampicillin <TextLink reference="38"></TextLink>.</Pgraph><Pgraph>Coumermycin, a substance which is not used in clinical medicine because of possible side-effects on blood coagulation, inhibits the subunit B of the bacterial gyrase. This agent is extremely active in vitro showing a bacteriostatic effect at quite low MIC values <TextLink reference="39"></TextLink>, <TextLink reference="40"></TextLink>.</Pgraph><SubHeadline2>Bactericidal activity of aminoglycosides and synergy with betalactams </SubHeadline2><Pgraph>Gentamicin is bactericidal against clinical isolates of <TextGroup><PlainText>L. m</PlainText></TextGroup>onocytogenes <TextLink reference="41"></TextLink>. In combination with betalactams a synergistic effect can be observed <TextLink reference="25"></TextLink>, <TextLink reference="41"></TextLink>. In particular the killing of Listeriae can be definitely augmented, presumably because the penetration of aminoglycoside molecules through the compact network of the cell wall of the grampositive bacteria can be facilitated by the softening of the peptidoglycan layers by ampicillin. Furthermore, it has to be kept in mind that even at subinh<TextGroup><PlainText>ib</PlainText></TextGroup>itory concentrations gentamicin is able to inhibit the production of essential bacterial virulence factors such as listeriolysin <TextLink reference="42"></TextLink>.</Pgraph><SubHeadline>The impact of intracellular habitat of L. monocytogenes on activities of antibiotics </SubHeadline><Pgraph>The basic structure of the host cell membrane is a lipid bylayer that acts as a definite barrier for free, passive diffusion of most but not all antibiotics <TextLink reference="43"></TextLink>. Hence, most antibiotics have only poor access to intracellular sites <TextLink reference="44"></TextLink>.</Pgraph><Pgraph>a) <Mark1>Fosfomycin:</Mark1> L. monocytogenes is naturally resistant in vitro to fosfomycin, because under the chosen conditions the drug is not taken up by the bacteria <TextLink reference="45"></TextLink>. Additionally, some strains may possess target mutations as well as enzymes hydrating the compound rendering the bacterium highly resistant <TextLink reference="46"></TextLink>. Paradoxically, in vivo <TextGroup><PlainText>L. m</PlainText></TextGroup>onocytogenes appears to be susceptible, which is due to the fact that once in an cytosolic compartment certain virulence factors such as listeriolysin O, phospholipases and ActA are produced and coexpressed with an hexose-phosphate inward transporter transporting also fosfomycin into the bacterial cells, where it can exert its antibacterial effect <TextLink reference="45"></TextLink>.</Pgraph><Pgraph>b) <Mark1>&#946;-lactams:</Mark1> Penicillin derivatives at least in their ionized form, reacting as weak organic acids, are able to diffuse slowly across the host membrane. The absolute amounts transported by this mechanism remains, however, is rather low. Storage takes place in the cytosol. Once the extracellular concentrations gets lower, the intracellular penicillin molecules can move in the opposite direction <TextLink reference="43"></TextLink>.</Pgraph><Pgraph>Amoxicillin is able to reduce the intracellular counts in infected cells at least when high extracellular concentrations are present <TextLink reference="44"></TextLink>.</Pgraph><Pgraph>Inspite of the relatively low intracellular concentrations the efficiency of ampicillin, amoxicillin and meropenem against intracellular Listeriae is higher than against extracellular ones. In fact time dependant killing is achieved at least after 24 hours <TextLink reference="44"></TextLink>, <TextLink reference="47"></TextLink>, whereas azlocillin, mezlocillin and cephalosporins were ineffective <TextLink reference="38"></TextLink>. One reason could be the fact that ampicillin in contrast to several other antibiotics was able to inhibit even in subinhibitory concentrations the production of hemolysin <TextLink reference="31"></TextLink>, a virulence factor which is essential for the intracellular life cycle of L. monocytogenes <TextLink reference="6"></TextLink>.</Pgraph><Pgraph>In experimental infections the effect of ampicillin was dependant on the dose and the time of the beginning of treatment. If treatment started rather early, the containment of bacteria was so effective, that an induction of an immune response to the bacteria could be prevented. Even in nude, athymic mice which are devoid of <TextGroup><PlainText>T ly</PlainText></TextGroup>mphocytes a marked reduction of the bacterial load was achieved but complete eradication was not be enforced. Obviously, without the cooperation of the host&#8217;s own immune system, a few bacteria survived and an exacerbation was observed in the immunocompromised mice few days after <TextLink reference="48"></TextLink>. Another process contributing to the curing effect of ampicillin is a host defense strategy against intracellular pathogens, i.e. the induction of cell death, thereby eliminating the pathogen&#39;s intracellular niche. Pyroptosis, one such form of cell death, is triggered, when intracellular Listeriae are lysed by ampicillin <TextLink reference="49"></TextLink>.</Pgraph><Pgraph>c) <Mark1>Gyrase inhibitors (quinolones&#47;coumermycin):</Mark1> The uptake of quinolones in eukaryotic cells takes place by passive diffusion, since these agents are amphiphilic; at least no carrier has been identified up to now. Whereas ciprofloxacin is a subject of active efflux mechanisms, moxifloxacin obviously remains unaffected <TextLink reference="50"></TextLink>. </Pgraph><Pgraph>Moxifloxacin is concentration dependant rapidly bactericidal in vitro and active against intracellular Listeria in cultured cells <TextLink reference="36"></TextLink>, <TextLink reference="47"></TextLink>, <TextLink reference="51"></TextLink>. Moxifloxacin has a rapid bactericidal effect against intracellular reservoirs of bacteria, whereas amoxicillin is only bacteriostatic <TextLink reference="51"></TextLink>. Whereas ciprofloxacin is a substrate for efflux pumps, so that Listeriae residing in host cells expressing these transporters, moxifloxacin is not and remains active <TextLink reference="52"></TextLink>.</Pgraph><Pgraph>In experimental infections with infestation of internal organs where Listeriae reside mostly intracellular, moxifloxacin was superior to ciprofloxacin as well as to ampicillin <TextLink reference="36"></TextLink>. Also in experimental models of Listeria meningitis, where bacteria predominantly multiply extracellularly, moxifloxacin was highly effective <TextLink reference="53"></TextLink>, <TextLink reference="54"></TextLink>.</Pgraph><Pgraph>The most active agent in the experimental setting was coumermycin, a gyrase B inhibitor. In experimental infections of the mouse coumermycin exerting a strong bactericidal activity in vitro could eliminate the bacteria even in immunocompromised nude mice <TextLink reference="37"></TextLink>. This duty was accomplished so efficiently that the mice were not compelled to mount an immune reaction. In comparison to all other antibiotics tested it was by far the most active drug <TextLink reference="55"></TextLink>.</Pgraph><Pgraph>d) <Mark1>Macrolides:</Mark1> Erythromycin as well as other macrolides are bacteriostatic against L. monocytogenes in vitro <TextLink reference="56"></TextLink>. The activity on intracellular bacteria is depending on the extracellular concentration <TextLink reference="7"></TextLink>. Since it is known, that macrolides loose activity at low pH <TextLink reference="57"></TextLink>, it can be anticipated that it does not act on bacteria lying in the phagocytic vacuole. But once Listeriae have escaped into the cytoplasm, it can work. There is, however, a risk that the host cell has overexpressed efflux pumps due to genetic or environmental conditions; in such cases the macrolide antibiotic cannot reach the intracellular bacteria and is unable to cure the infection of those host cells <TextLink reference="7"></TextLink>.</Pgraph><Pgraph>In experimental infections of normal mice erythromycin is able to inhibit bacterial multiplication. In immunocompromised animals without the aid of the body&#8217;s own defense system the protective effect was rather low <TextLink reference="56"></TextLink>.</Pgraph><Pgraph> </Pgraph><Pgraph>e) <Mark1>Tetracyclines:</Mark1> In vitro tetracycline is bacteriostatic for L. monocytogenes <TextLink reference="58"></TextLink>. In various mouse models (normal adult mice, nude, macrophage deprived animals, baby mice) this antibiotic was able to reduce the bacteria multiplication <TextLink reference="58"></TextLink>.</Pgraph><Pgraph>f) <Mark1>Cotrimoxazole:</Mark1> Trimethoprim is rather active in vitro against L. monocytogenes, whereas the sulfonamide component alone is rather inactive. In combination there is a synergistic effect <TextLink reference="59"></TextLink>.</Pgraph><Pgraph>This lipophilic drug is taken up by host cells via diffusion <TextLink reference="43"></TextLink> and is active against intracellular Listeriae <TextLink reference="38"></TextLink>. In experimental infections of normal and immunocompromised mice a definite therapeutic effect was observed <TextLink reference="59"></TextLink>.</Pgraph><Pgraph>g) <Mark1>Aminoglycosides:</Mark1> Aminoglycosides are taken up actively into host cells by fluid-phase pinocytosis. Thereby, substances dissolved in the extracellular fluid are internalized. The rate at which vesicles are transported varies from cell type to cell type but is in general relatively high. Thus, after a few minutes and even hours the absolute amounts of intracellular drug is still low but can be remarkable after several days. After penetration the agents are not distributed evenly in the cytosol but are avidly trapped into the lysosomes. Within these longlasting reservoirs characterized by a low pH, aminoglycosides are stored in their cationic, i.e. microbiologically inactive forms, and are released only very slowly over a period of several days <TextLink reference="43"></TextLink>.</Pgraph><Pgraph>Consequently, aminoglycosides can only be active against extracellular bacteria. Indeed, no activity against intracellular Listeriae in host cells was detected <TextLink reference="38"></TextLink>, <TextLink reference="44"></TextLink>, <TextLink reference="47"></TextLink>.</Pgraph><Pgraph>Furthermore, a lack of synergism with ampicillin was also observed in experimental listeriosis when bacteria reside mainly intracellularly <TextLink reference="60"></TextLink>.</Pgraph><Pgraph>h) <Mark1>Rifampicin:</Mark1> Rifampicin is bactericidal for L. monocytogenes in vitro <TextLink reference="61"></TextLink>. This lipophilic drug easily penetrates through the lipid bilayer of the host cell membrane <TextLink reference="43"></TextLink>, and it acts on intracellular L. monocytogenes about <TextGroup><PlainText>200 times</PlainText></TextGroup> more effectively than ampicillin <TextLink reference="62"></TextLink>. Furthermore, in experimental infection, when Listeriae multiply mainly in the reticuloendothelial organs such as spleen and liver, it is highly effective <TextLink reference="62"></TextLink> and even in compromised hosts, such as nude mice, deprived of T-lymphocytes, rifampicin is able to reduce the bacterial load although a complete eradication was not achieved <TextLink reference="63"></TextLink>. When bacteria multiply extracellularly, like in a meningitis model, it is, however less active than ampicillin <TextLink reference="64"></TextLink>.</Pgraph><Pgraph>i) <Mark1>Glycopeptides (vancomycin&#47;teicoplanin&#47;daptomycin):</Mark1> Listeria monocytogenes is susceptible in vitro to vancomycin and teicoplanin <TextLink reference="65"></TextLink> as well as to daptomycin <TextLink reference="66"></TextLink>. According to a recent report Listeria grayi is resistant to vancomycin <TextLink reference="67"></TextLink>.</Pgraph><Pgraph>In experimental infections of normal mice only a poor therapeutic activity of both vancomycin and teicoplanin <TextLink reference="65"></TextLink> was seen and daptomycin was completely ineffective <TextLink reference="66"></TextLink>. In athymic nude mice, which are immunocompromised, no activity of teicoplanin was seen <TextLink reference="65"></TextLink>.</Pgraph><Pgraph>One explanation for this discrepancy between in vitro and in vivo activities could be that these compounds are inactive against intracellular bacteria, because they may remain adherent to the cytoplasmic membrane of host cells after penetration, so that finally they do not come into contact with the microbe in the phagocytic vacuole or in the cytoplasm, respectively <TextLink reference="43"></TextLink>.</Pgraph><Pgraph> j) <Mark1>Linezolid:</Mark1> This oxazolidinone is active against all grampositive bacteria including Listeria monocytogenes exerting a bacteriostatic effect <TextLink reference="68"></TextLink>. In addition the growth of bacteria within host cells was inhibited <TextLink reference="68"></TextLink>. Mice infected intravenously or intracerebrally were protected, although linezolid was less efficient than ampicillin <TextLink reference="68"></TextLink>. Clinical experience with linezolid is limited but promising <TextLink reference="69"></TextLink> possibly, because linezolid is found in high concentrations in CSF <TextLink reference="70"></TextLink>.</Pgraph><Pgraph>k) <Mark1>Combinations:</Mark1> Although in vitro a definite synergistic effect between &#946;-lactams and aminoglycosides can be seen <TextLink reference="23"></TextLink>, <TextLink reference="39"></TextLink>, there is no such phenomenon observed on intracellular Listeriae <TextLink reference="44"></TextLink>. Furthermore, a lack of synergism of gentamicin with ampicillin was also registered in experimental listeriosis <TextLink reference="60"></TextLink>, when bacteria reside mainly intracellularly.</Pgraph><Pgraph>Combination of antibiotics are better than single drugs not only because of a possible in vitro synergism; in case of a combination of ampicillin and rifampicin it could be argued that both agents would penetrate into the host cells as well as into different compartments of a host in different degrees and pathways and may exert additive effects.</Pgraph><Pgraph>Combinations of antibiotics with anti-inflammatory agents such as diclofenac may be synergistic <TextLink reference="71"></TextLink>.</Pgraph><SubHeadline>The impact of the site of Listeria infection. Location at remote sites hardly accesible for antibiotics and the microenvironment on efficacy of antimicrobial therapy</SubHeadline><SubHeadline2>CSF </SubHeadline2><Pgraph>Because of the blood brain barrier the entry of antibiotics into the CNS is restricted <TextLink reference="72"></TextLink>. Whereas linezolid <TextLink reference="70"></TextLink>, rifampicin and quinolones <TextLink reference="72"></TextLink> and especially moxifloxacin <TextLink reference="73"></TextLink> are found in high concentrations in the cerebrospinal fluid, &#946;-lactam antibiotics including ampicillin as well as amoxycillin penetrate the blood brain barrier only poorly <TextLink reference="72"></TextLink>. Furthermore, in an inflammatory CSF the pH is rather low due to massive lactate production (&#62;3.5 nmol&#47;l) so that there is a risk that the labile &#946;-lactam ring will be cleaved catalytically <TextLink reference="74"></TextLink>. Ampicillin as well as amoxycilin, however, are relatively acid stable <TextLink reference="75"></TextLink>. Macrolides also lose activity at low pH <TextLink reference="57"></TextLink>.</Pgraph><SubHeadline2>Granuloma</SubHeadline2><Pgraph>After a few days of infection with L. monocytogenes a granulomatous reaction is created by the host <TextLink reference="13"></TextLink>, <TextLink reference="76"></TextLink>, so the cells infected with Listeriae are surrounded by a dense wall of lymphocytes. Lipophilic compounds such as rifampicin and quinolones generally penetrate better such anatomic barriers than hydrophilic, ionized drugs <TextLink reference="72"></TextLink>. Thus, complete eradication can only hardly be achieved by ampicillin.</Pgraph><SubHeadline2>Placental barrier</SubHeadline2><Pgraph>A few antibiotics only cross the placenta rapidly; among these is ampicillin. Other antibiotics such as piperacillin, cefoxitin, gentamicin, fosfomycin and vancomycin show incomplete transfer to the placenta where concentrations are lower in the cord than maternal plasma <TextLink reference="77"></TextLink>. The placental transfer of macrolides is generally low; among them clarithromycin achieves the relatively highest concentrations <TextLink reference="78"></TextLink>. </Pgraph></TextBlock> <TextBlock linked="yes" name="Therapeutic options"> <MainHeadline>Therapeutic options</MainHeadline><SubHeadline>Current therapeutic approaches </SubHeadline><Pgraph>The local inoculation of L. monocytogenes in the skin or in the conjunctiva may induce localized infections in otherwise healthy people. In general, these superficial infections as well as the gastrointestinal manifestations are self-limited. Occasionally, however, such local infections need appropriate systemic therapy to resolve <TextLink reference="79"></TextLink>.</Pgraph><Pgraph>Antibiotics given to a patient are seldom able to overcome an infection without the contribution of the defense system <TextLink reference="80"></TextLink>. Since systemic listeriosis occurs mainly in immunocompromised patients, it is quite conceivable that curing is not always possible, even if the best antibiotics have been chosen. Bactericidal activity of an antibiotic seems to be an advantage. Furthermore, in most cases, the infection happens in the CNS, which remains hardly accessible for most antibiotics due to the blood-brain-barrier. Consequently, the mortality remains high, i.e. up to 25&#37;, and sequelae are frequent instead of rational antibiotic treatment.</Pgraph><Pgraph>Drug of primary choice remains ampicillin or even more so amoxicillin. Ureidopenicillins and carbapenems are also active but not superior to aminopenicillins. High doses, for example 2&#8211;3 g ampicillin given 3&#8211;4 times a day, are recommended. This regimen should be given at least for 2&#8211;3 weeks, even if the clinical conditions have improved in the meantime, to prevent a relapse. Because a total eradication is difficult to achieve without the body&#8217;s own defense system, it is even prudent especially in cases of encephalitis in strongly immunocompromised patients to continue the regimen for about 2&#8211;6 weeks to avoid exacerbation; in this case an oral application of aminopenicillin could be advised to eliminate reservoirs of bacteria. In case of relapse the same regimen can be given, since this is not due to resistance, since until now the clinical isolates are unanimously susceptible to ampicillin. A poor response to rational antimicrobial therapy rather results from the remote place of infection hardly accessible for antibiotics or from the weak host&#8217;s defense as a natural consequence of the underlying disease. </Pgraph><Pgraph>Because there is a synergistic effect in vitro of combinations of &#946;-lactams with aminogylcosides against L. moncyotogenes <TextLink reference="25"></TextLink>, <TextLink reference="41"></TextLink>, it has been widely accepted that this combination would be the therapy of choice especially for the treatment of CNS infections and endocarditis <TextLink reference="25"></TextLink>. In cell cultures and animal experiments, however, this effect is lacking. A review of a large number of cases of CNS infections has shown a superiority of this combination <TextLink reference="81"></TextLink>. But there is growing evidence that this combination does not provide a definite advantage over an aminopenicillin alone <TextLink reference="82"></TextLink>, <TextLink reference="83"></TextLink>. But the debate is still ongoing <TextLink reference="84"></TextLink>. In any case the aminoglycoside has to be omitted after 2 weeks, because of potential nephrotoxicity, especially in the elderly.</Pgraph><Pgraph>In case of allergy to penicillins parenteral application of cotrimoxazole (for example 80 mg trimethoprim and <TextGroup><PlainText>400 mg</PlainText></TextGroup> sulfamethoxazole q.i.d for six weeks), is recommended as therapy of second choice, since this drug combination is bactericidal for L. monocytogenes in vitro and is accumulated within host cells and finds access to the CNS as well as to the placenta. This drug or trimethoprim alone can also be used for oral follow-up treatment after an initial parenteral application also after initial therapy with amoxicillin <TextLink reference="7"></TextLink>, <TextLink reference="25"></TextLink>, when the predisposing factors are still persisting so that an endogenous exacerbation could take place. Even a combination of amoxicillin and cotrimoxazole could be advised <TextLink reference="85"></TextLink>. Because of a possible risk for the fetus &#8211; at least shown by animal experiments &#8211; cotrimoxazole should be avoided during pregnancy.</Pgraph><Pgraph>On the other hand a combination of amoxicillin with rifampicin in the therapy of cerebral listeriosis gives sense, since rifampicin can penetrate quite well into the CSF and can act on intracellular bacteria <TextLink reference="25"></TextLink>. A final view, however, is impossible, because the clinical experience is limited.</Pgraph><Pgraph>Macrolides and tetracyclines are no more recommended today for the therapy of human listeriosis <TextLink reference="86"></TextLink>.</Pgraph><Pgraph>Unfortunately, in some guidelines it has been recommended to start calculated therapy of presumptive bacterial meningitis with ceftriaxone as monotherapy <TextLink reference="16"></TextLink>. This cephalosporine is, however, inherently inactive against L. monocytogenes. Hence, the beginning of an effective antimicrobial therapy of listeric meningitis is delayed which implicates a worse outcome. Therefore, ampicillin should be added according to the German Society of Neurology <TextLink reference="87"></TextLink>, in particular in those individuals prone to Listeria infections, namely in aged people and in immunocompromised patients. </Pgraph><SubHeadline>Future trends (including novel agents&#47;approaches) </SubHeadline><Pgraph>There is ample evidence that moxifloxacin is qualified to replace ampicillin as therapy of the first choice. It is ra<TextGroup><PlainText>pi</PlainText></TextGroup>dly bactericidal at low concentrations <TextLink reference="36"></TextLink>, <TextLink reference="47"></TextLink>, <TextLink reference="51"></TextLink>, it is accumulated in host cells and remains active under such special conditions <TextLink reference="47"></TextLink>. In animal experiments it is able to reduce the bacterial load &#8211; even in immunocompromised animals <TextLink reference="36"></TextLink>, <TextLink reference="53"></TextLink>, <TextLink reference="54"></TextLink>. Furthermore, it is highly active in CSF <TextLink reference="73"></TextLink>. Since large clinical experience is still lacking, it cannot be unanimously recommended for therapy of listeriosis yet. Successful clinical experience exists at least with another, similar quinolone namely levofloxacin <TextLink reference="88"></TextLink>. It should be kept in mind, however, that quinolones are not allowed during pregnancy.</Pgraph><SubHeadline>Adjunctive therapy</SubHeadline><Pgraph>Some authorities have proposed a treatment with dexamethasone to reduce an excessive inflammatory response during bacterial meningitis <TextLink reference="16"></TextLink>, <TextLink reference="87"></TextLink>, which otherwise may have deleterious effects. On the other hand this co-medication may have some influence on the pharmacodynamics of some antibiotics, especially vancomycin <TextLink reference="16"></TextLink>, <TextLink reference="72"></TextLink>, <TextLink reference="89"></TextLink>.</Pgraph><Pgraph>Combinations of antibiotics with other anti-inflammatory agents such as diclofenac may have synergistic effects with antibiotics <TextLink reference="71"></TextLink>.</Pgraph><SubHeadline>Unconventional approaches</SubHeadline><Pgraph>Inspite of a rational antibiotic therapy the prognosis of Listeria infections remains poor. Therefore, it is quite logic to look for other even unconventional approaches. Lactoferrin has several interesting effects on L. monocytogenes in vitro <TextLink reference="90"></TextLink>, on Listeriae in cell cultures <TextLink reference="91"></TextLink> as well as on experimental listeriosis <TextLink reference="92"></TextLink>. Obviously, it exerts not only a direct antibacterial activity but also modulates the host defense. This aspect seems to be of special importance in the therapy of listeriosis occuring predominantly in patients with a compromised immune system. In general it is difficult yet to direct the immune system in the desired way without triggering an opposite effect.</Pgraph><Pgraph>Vaccinations strategies to prevent or to fight against listeriosis are not yet clinically available but experimental evidence is promising <TextLink reference="93"></TextLink>.</Pgraph></TextBlock> <TextBlock linked="yes" name="Notes"> <MainHeadline>Notes</MainHeadline><SubHeadline>Competing interests</SubHeadline><Pgraph>The author has received honoraria for lectures and conferences from Bayer, MSD, Novartis, Pfizer. </Pgraph><SubHeadline>Funding</SubHeadline><Pgraph>For this review the author has not received any grants.</Pgraph></TextBlock> <References linked="yes"> <Reference refNo="1"> <RefAuthor>Graves LM</RefAuthor> <RefAuthor>Helsel LO</RefAuthor> <RefAuthor>Steigerwalt AG</RefAuthor> <RefAuthor>Morey RE</RefAuthor> <RefAuthor>Daneshvar MI</RefAuthor> <RefAuthor>Roof SE</RefAuthor> <RefAuthor>Orsi RH</RefAuthor> <RefAuthor>Fortes ED</RefAuthor> <RefAuthor>Milillo SR</RefAuthor> <RefAuthor>den Bakker HC</RefAuthor> <RefAuthor>Wiedmann M</RefAuthor> <RefAuthor>Swaminathan B</RefAuthor> <RefAuthor>Sauders BD</RefAuthor> <RefTitle>Listeria marthii sp. nov., isolated from the natural environment, Finger Lakes National Forest</RefTitle> <RefYear>2010</RefYear> <RefJournal>Int J Syst Evol Microbiol</RefJournal> <RefPage>1280-8</RefPage> <RefTotal>Graves LM, Helsel LO, Steigerwalt AG, Morey RE, Daneshvar MI, Roof SE, Orsi RH, Fortes ED, Milillo SR, den Bakker HC, Wiedmann M, Swaminathan B, Sauders BD. Listeria marthii sp. nov., isolated from the natural environment, Finger Lakes National Forest. Int J Syst Evol Microbiol. 2010 Jun;60(Pt 6):1280-8. DOI: 10.1099&#47;ijs.0.014118-0</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1099&#47;ijs.0.014118-0</RefLink> </Reference> <Reference refNo="2"> <RefAuthor>Leclercq A</RefAuthor> <RefAuthor>Clermont D</RefAuthor> <RefAuthor>Bizet C</RefAuthor> <RefAuthor>Grimont PA</RefAuthor> <RefAuthor>Le Fl&#232;che-Mat&#233;os A</RefAuthor> <RefAuthor>Roche SM</RefAuthor> <RefAuthor>Buchrieser C</RefAuthor> <RefAuthor>Cadet-Daniel V</RefAuthor> <RefAuthor>Le Monnier A</RefAuthor> <RefAuthor>Lecuit M</RefAuthor> <RefAuthor>Allerberger F</RefAuthor> <RefTitle>Listeria rocourtiae sp. nov</RefTitle> <RefYear>2010</RefYear> <RefJournal>Int J Syst Evol Microbiol</RefJournal> <RefPage>2210-4</RefPage> <RefTotal>Leclercq A, Clermont D, Bizet C, Grimont PA, Le Fl&#232;che-Mat&#233;os A, Roche SM, Buchrieser C, Cadet-Daniel V, Le Monnier A, Lecuit M, Allerberger F. Listeria rocourtiae sp. nov. Int J Syst Evol Microbiol. 2010 Sep;60(Pt 9):2210-4. DOI: 10.1099&#47;ijs.0.017376-0</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1099&#47;ijs.0.017376-0</RefLink> </Reference> <Reference refNo="3"> <RefAuthor>Bertsch D</RefAuthor> <RefAuthor>Rau J</RefAuthor> <RefAuthor>Eugster MR</RefAuthor> <RefAuthor>Haug MC</RefAuthor> <RefAuthor>Lawson PA</RefAuthor> <RefAuthor>Lacroix C</RefAuthor> <RefAuthor>Meile L</RefAuthor> <RefTitle>Listeria fleischmannii sp. nov., isolated from cheese</RefTitle> <RefYear>2013</RefYear> <RefJournal>Int J Syst Evol Microbiol</RefJournal> <RefPage>526-32</RefPage> <RefTotal>Bertsch D, Rau J, Eugster MR, Haug MC, Lawson PA, Lacroix C, Meile L. Listeria fleischmannii sp. nov., isolated from cheese. Int J Syst Evol Microbiol. 2013 Feb;63(Pt 2):526-32. DOI: 10.1099&#47;ijs.0.036947-0</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1099&#47;ijs.0.036947-0</RefLink> </Reference> <Reference refNo="4"> <RefAuthor>Lang Halter E</RefAuthor> <RefAuthor>Neuhaus K</RefAuthor> <RefAuthor>Scherer S</RefAuthor> <RefTitle>Listeria weihenstephanensis sp. nov., isolated from the water plant Lemna trisulca taken from a freshwater pond</RefTitle> <RefYear>2013</RefYear> <RefJournal>Int J Syst Evol Microbiol</RefJournal> <RefPage>641-7</RefPage> <RefTotal>Lang Halter E, Neuhaus K, Scherer S. Listeria weihenstephanensis sp. nov., isolated from the water plant Lemna trisulca taken from a freshwater pond. Int J Syst Evol Microbiol. 2013 Feb;63(Pt 2):641-7. DOI: 10.1099&#47;ijs.0.036830-0</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1099&#47;ijs.0.036830-0</RefLink> </Reference> <Reference refNo="5"> <RefAuthor>Hof H</RefAuthor> <RefTitle>Virulence of different strains of Listeria monocytogenes serovar 1&#47;2a</RefTitle> <RefYear>1984</RefYear> <RefJournal>Med Microbiol Immunol</RefJournal> <RefPage>207-18</RefPage> <RefTotal>Hof H. Virulence of different strains of Listeria monocytogenes serovar 1&#47;2a. Med Microbiol Immunol. 1984;173(4):207-18. DOI: 10.1007&#47;BF02122112</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1007&#47;BF02122112</RefLink> </Reference> <Reference refNo="6"> <RefAuthor>Portnoy DA</RefAuthor> <RefAuthor>Chakraborty T</RefAuthor> <RefAuthor>Goebel W</RefAuthor> <RefAuthor>Cossart P</RefAuthor> <RefTitle>Molecular determinants of Listeria monocytogenes pathogenesis</RefTitle> <RefYear>1992</RefYear> <RefJournal>Infect Immun</RefJournal> <RefPage>1263-7</RefPage> <RefTotal>Portnoy DA, Chakraborty T, Goebel W, Cossart P. Molecular determinants of Listeria monocytogenes pathogenesis. Infect Immun. 1992 Apr;60(4):1263-7.</RefTotal> </Reference> <Reference refNo="7"> <RefAuthor>Hof H</RefAuthor> <RefAuthor>Nichterlein T</RefAuthor> <RefAuthor>Kretschmar M</RefAuthor> <RefTitle>Management of listeriosis</RefTitle> <RefYear>1997</RefYear> <RefJournal>Clin Microbiol Rev</RefJournal> <RefPage>345-57</RefPage> <RefTotal>Hof H, Nichterlein T, Kretschmar M. Management of listeriosis. Clin Microbiol Rev. 1997 Apr;10(2):345-57.</RefTotal> </Reference> <Reference refNo="8"> <RefAuthor>Gottlieb CT</RefAuthor> <RefAuthor>Thomsen LE</RefAuthor> <RefAuthor>Ingmer H</RefAuthor> <RefAuthor>Mygind PH</RefAuthor> <RefAuthor>Kristensen HH</RefAuthor> <RefAuthor>Gram L</RefAuthor> <RefTitle>Antimicrobial peptides effectively kill a broad spectrum of Listeria monocytogenes and Staphylococcus aureus strains independently of origin, sub-type, or virulence factor expression</RefTitle> <RefYear>2008</RefYear> <RefJournal>BMC Microbiol</RefJournal> <RefPage>205</RefPage> <RefTotal>Gottlieb CT, Thomsen LE, Ingmer H, Mygind PH, Kristensen HH, Gram L. Antimicrobial peptides effectively kill a broad spectrum of Listeria monocytogenes and Staphylococcus aureus strains independently of origin, sub-type, or virulence factor expression. BMC Microbiol. 2008;8:205. DOI: 10.1186&#47;1471-2180-8-205</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1186&#47;1471-2180-8-205</RefLink> </Reference> <Reference refNo="9"> <RefAuthor>Kretschmar M</RefAuthor> <RefAuthor>Budeanu C</RefAuthor> <RefAuthor>Nichterlein T</RefAuthor> <RefAuthor>Hof H</RefAuthor> <RefTitle>Wirkung von Mersacidin auf die murine Listeriose</RefTitle> <RefYear>1993</RefYear> <RefJournal>Chemotherapie Journal</RefJournal> <RefPage>176-8</RefPage> <RefTotal>Kretschmar M, Budeanu C, Nichterlein T, Hof H. Wirkung von Mersacidin auf die murine Listeriose. Chemotherapie Journal. 1993;2:176-8.</RefTotal> </Reference> <Reference refNo="10"> <RefAuthor>Pizarro-Cerd&#225; J</RefAuthor> <RefAuthor>K&#252;hbacher A</RefAuthor> <RefAuthor>Cossart P</RefAuthor> <RefTitle>Entry of Listeria monocytogenes in mammalian epithelial cells: an updated view</RefTitle> <RefYear>2012</RefYear> <RefJournal>Cold Spring Harb Perspect Med</RefJournal> <RefPage>pii:a010009</RefPage> <RefTotal>Pizarro-Cerd&#225; J, K&#252;hbacher A, Cossart P. Entry of Listeria monocytogenes in mammalian epithelial cells: an updated view. Cold Spring Harb Perspect Med. 2012 Nov;2(11):pii:a010009. DOI: 10.1101&#47;cshperspect.a010009</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1101&#47;cshperspect.a010009</RefLink> </Reference> <Reference refNo="11"> <RefAuthor>Geginat G</RefAuthor> <RefAuthor>Grauling-Halama S</RefAuthor> <RefTitle>Innate immunity</RefTitle> <RefYear>2008</RefYear> <RefBookTitle>Handbook of Listeria moncytogenes</RefBookTitle> <RefPage>397-426</RefPage> <RefTotal>Geginat G, Grauling-Halama S. Innate immunity. In: Liu D, editor. Handbook of Listeria moncytogenes. Boca Raton: CRC Press; 2008. p. 397-426. DOI: 10.1201&#47;9781420051414.ch13</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1201&#47;9781420051414.ch13</RefLink> </Reference> <Reference refNo="12"> <RefAuthor>Bakardjiev AI</RefAuthor> <RefAuthor>Stacy BA</RefAuthor> <RefAuthor>Portnoy DA</RefAuthor> <RefTitle>Growth of Listeria monocytogenes in the guinea pig placenta and role of cell-to-cell spread in fetal infection</RefTitle> <RefYear>2005</RefYear> <RefJournal>J Infect Dis</RefJournal> <RefPage>1889-97</RefPage> <RefTotal>Bakardjiev AI, Stacy BA, Portnoy DA. Growth of Listeria monocytogenes in the guinea pig placenta and role of cell-to-cell spread in fetal infection. J Infect Dis. 2005 Jun;191(11):1889-97. DOI: 10.1086&#47;430090</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1086&#47;430090</RefLink> </Reference> <Reference refNo="13"> <RefAuthor>Schl&#252;ter D</RefAuthor> <RefAuthor>Chahoud S</RefAuthor> <RefAuthor>Lassmann H</RefAuthor> <RefAuthor>Schumann A</RefAuthor> <RefAuthor>Hof H</RefAuthor> <RefAuthor>Deckert-Schl&#252;ter M</RefAuthor> <RefTitle>Intracerebral targets and immunomodulation of murine Listeria monocytogenes meningoencephalitis</RefTitle> <RefYear>1996</RefYear> <RefJournal>J Neuropathol Exp Neurol</RefJournal> <RefPage>14-24</RefPage> <RefTotal>Schl&#252;ter D, Chahoud S, Lassmann H, Schumann A, Hof H, Deckert-Schl&#252;ter M. Intracerebral targets and immunomodulation of murine Listeria monocytogenes meningoencephalitis. J Neuropathol Exp Neurol. 1996 Jan;55(1):14-24. DOI: 10.1097&#47;00005072-199601000-00002</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1097&#47;00005072-199601000-00002</RefLink> </Reference> <Reference refNo="14"> <RefAuthor>Pamer EG</RefAuthor> <RefTitle>Immune responses to Listeria monocytogenes</RefTitle> <RefYear>2004</RefYear> <RefJournal>Nat Rev Immunol</RefJournal> <RefPage>812-23</RefPage> <RefTotal>Pamer EG. Immune responses to Listeria monocytogenes. Nat Rev Immunol. 2004 Oct;4(10):812-23. DOI: 10.1038&#47;nri1461</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1038&#47;nri1461</RefLink> </Reference> <Reference refNo="15"> <RefAuthor>Heymer B</RefAuthor> <RefAuthor>Hof H</RefAuthor> <RefAuthor>Emmerling P</RefAuthor> <RefAuthor>Finger H</RefAuthor> <RefTitle>Morphology and time course of experimental listeriosis in nude mice</RefTitle> <RefYear>1976</RefYear> <RefJournal>Infect Immun</RefJournal> <RefPage>832-5</RefPage> <RefTotal>Heymer B, Hof H, Emmerling P, Finger H. Morphology and time course of experimental listeriosis in nude mice. Infect Immun. 1976 Sep;14(3):832-5.</RefTotal> </Reference> <Reference refNo="16"> <RefAuthor>Nudelman Y</RefAuthor> <RefAuthor>Tunkel AR</RefAuthor> <RefTitle>Bacterial meningitis: epidemiology, pathogenesis and management update</RefTitle> <RefYear>2009</RefYear> <RefJournal>Drugs</RefJournal> <RefPage>2577-96</RefPage> <RefTotal>Nudelman Y, Tunkel AR. Bacterial meningitis: epidemiology, pathogenesis and management update. Drugs. 2009;69(18):2577-96. DOI: 10.2165&#47;11530590-000000000-00000</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.2165&#47;11530590-000000000-00000</RefLink> </Reference> <Reference refNo="17"> <RefAuthor>Koch J</RefAuthor> <RefAuthor>Stark K</RefAuthor> <RefTitle>Significant increase of listeriosis in Germany &#8211; epidemiological patterns 2001&#8211;2005</RefTitle> <RefYear>2006</RefYear> <RefJournal>Euro Surveill</RefJournal> <RefPage>85-8</RefPage> <RefTotal>Koch J, Stark K. Significant increase of listeriosis in Germany &#8211; epidemiological patterns 2001&#8211;2005. Euro Surveill. 2006;11(6):85-8.</RefTotal> </Reference> <Reference refNo="18"> <RefAuthor>Murphy G</RefAuthor> <RefAuthor>Schmidt-Martin D</RefAuthor> <RefAuthor>Hynes BG</RefAuthor> <RefAuthor>Harney S</RefAuthor> <RefTitle>Systemic listeriosis with adalimumab therapy</RefTitle> <RefYear>2009</RefYear> <RefJournal>J Clin Rheumatol</RefJournal> <RefPage>369-70</RefPage> <RefTotal>Murphy G, Schmidt-Martin D, Hynes BG, Harney S. Systemic listeriosis with adalimumab therapy. J Clin Rheumatol. 2009 Oct;15(7):369-70. DOI: 10.1097&#47;RHU.0b013e3181bf93cd</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1097&#47;RHU.0b013e3181bf93cd</RefLink> </Reference> <Reference refNo="19"> <RefAuthor>Hof H</RefAuthor> <RefAuthor>Lampidis R</RefAuthor> <RefTitle>Retrospective evidence for nosocomial Listeria infection</RefTitle> <RefYear>2001</RefYear> <RefJournal>J Hosp Infect</RefJournal> <RefPage>321-2</RefPage> <RefTotal>Hof H, Lampidis R. Retrospective evidence for nosocomial Listeria infection. J Hosp Infect. 2001 Aug;48(4):321-2. DOI: 10.1053&#47;jhin.2001.0999</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1053&#47;jhin.2001.0999</RefLink> </Reference> <Reference refNo="20"> <RefAuthor>Painter J</RefAuthor> <RefAuthor>Slutsker L</RefAuthor> <RefTitle>Listeriosis in humans</RefTitle> <RefYear>2007</RefYear> <RefBookTitle>Listeria, listeriosis, and Food Safety</RefBookTitle> <RefPage>85-109</RefPage> <RefTotal>Painter J, Slutsker L. Listeriosis in humans. In: Ryser ET, Marth EH, editors. Listeria, listeriosis, and Food Safety. 3rd ed. Boca Raton: CRC Press; 2007. p. 85-109. DOI: 10.1201&#47;9781420015188.ch4</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1201&#47;9781420015188.ch4</RefLink> </Reference> <Reference refNo="21"> <RefAuthor>Janakiraman V</RefAuthor> <RefTitle>Listeriosis in pregnancy: diagnosis, treatment, and prevention</RefTitle> <RefYear>2008</RefYear> <RefJournal>Rev Obstet Gynecol</RefJournal> <RefPage>179-85</RefPage> <RefTotal>Janakiraman V. Listeriosis in pregnancy: diagnosis, treatment, and prevention. Rev Obstet Gynecol. 2008;1(4):179-85.</RefTotal> </Reference> <Reference refNo="22"> <RefAuthor>Hof H</RefAuthor> <RefAuthor>Szabo K</RefAuthor> <RefAuthor>Becker B</RefAuthor> <RefTitle>Epidemiologie der Listeriose in Deutschland &#8211; im Wandel und dennoch nicht beachtet</RefTitle> <RefYear>2007</RefYear> <RefJournal>Dtsch Med Wochenschr</RefJournal> <RefPage>1343-8</RefPage> <RefTotal>Hof H, Szabo K, Becker B. Epidemiologie der Listeriose in Deutschland &#8211; im Wandel und dennoch nicht beachtet &#91;Epidemiology of listeriosis in Germany: a changing but ignored pattern&#93;. Dtsch Med Wochenschr. 2007 Jun;132(24):1343-8. DOI: 10.1055&#47;s-2007-982034</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1055&#47;s-2007-982034</RefLink> </Reference> <Reference refNo="23"> <RefAuthor>Jorgensen JH</RefAuthor> <RefAuthor>Hindler JA</RefAuthor> <RefAuthor>Bernard K</RefAuthor> <RefAuthor>Citron DM</RefAuthor> <RefAuthor>Cockerill FR III</RefAuthor> <RefAuthor>Fritsche TR</RefAuthor> <RefAuthor></RefAuthor> <RefTitle></RefTitle> <RefYear>2010</RefYear> <RefBookTitle>Methods for antimicrobial dilution and disk susceptibility testing of infrequently isolated or fastidious bacteria. Approved guideline.</RefBookTitle> <RefPage>29</RefPage> <RefTotal>Jorgensen JH, Hindler JA, Bernard K, Citron DM, Cockerill FR III, Fritsche TR, et al. Methods for antimicrobial dilution and disk susceptibility testing of infrequently isolated or fastidious bacteria. Approved guideline. Second edition. M-45-A2. Vol. 30, no. 18. CLSI; 2010. p. 29.</RefTotal> </Reference> <Reference refNo="24"> <RefAuthor>Morvan A</RefAuthor> <RefAuthor>Moubareck C</RefAuthor> <RefAuthor>Leclercq A</RefAuthor> <RefAuthor>Herv&#233;-Bazin M</RefAuthor> <RefAuthor>Bremont S</RefAuthor> <RefAuthor>Lecuit M</RefAuthor> <RefAuthor>Courvalin P</RefAuthor> <RefAuthor>Le Monnier A</RefAuthor> <RefTitle>Antimicrobial resistance of Listeria monocytogenes strains isolated from humans in France</RefTitle> <RefYear>2010</RefYear> <RefJournal>Antimicrob Agents Chemother</RefJournal> <RefPage>2728-31</RefPage> <RefTotal>Morvan A, Moubareck C, Leclercq A, Herv&#233;-Bazin M, Bremont S, Lecuit M, Courvalin P, Le Monnier A. Antimicrobial resistance of Listeria monocytogenes strains isolated from humans in France. Antimicrob Agents Chemother. 2010 Jun;54(6):2728-31. DOI: 10.1128&#47;AAC.01557-09</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1128&#47;AAC.01557-09</RefLink> </Reference> <Reference refNo="25"> <RefAuthor>Hof H</RefAuthor> <RefTitle>An update on the medical management of listeriosis</RefTitle> <RefYear>2004</RefYear> <RefJournal>Expert Opin Pharmacother</RefJournal> <RefPage>1727-35</RefPage> <RefTotal>Hof H. An update on the medical management of listeriosis. Expert Opin Pharmacother. 2004 Aug;5(8):1727-35. DOI: 10.1517&#47;14656566.5.8.1727</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1517&#47;14656566.5.8.1727</RefLink> </Reference> <Reference refNo="26"> <RefAuthor>Sand S</RefAuthor> <RefAuthor>Becker B</RefAuthor> <RefAuthor>Hof H</RefAuthor> <RefTitle>Derzeit keine erkennbare Gefahr der Resistenzentwicklung bei Listeria monocytogenes</RefTitle> <RefYear>2009</RefYear> <RefJournal>Arch Lebensmittelhyg</RefJournal> <RefPage>18-22</RefPage> <RefTotal>Sand S, Becker B, Hof H. Derzeit keine erkennbare Gefahr der Resistenzentwicklung bei Listeria monocytogenes. Arch Lebensmittelhyg. 2009;60(1):18-22.</RefTotal> </Reference> <Reference refNo="27"> <RefAuthor>Charpentier E</RefAuthor> <RefAuthor>Courvalin P</RefAuthor> <RefTitle>Antibiotic resistance in Listeria spp</RefTitle> <RefYear>1999</RefYear> <RefJournal>Antimicrob Agents Chemother</RefJournal> <RefPage>2103-8</RefPage> <RefTotal>Charpentier E, Courvalin P. Antibiotic resistance in Listeria spp. Antimicrob Agents Chemother. 1999 Sep;43(9):2103-8.</RefTotal> </Reference> <Reference refNo="28"> <RefAuthor>Njagi LW</RefAuthor> <RefAuthor>Mbuthia PG</RefAuthor> <RefAuthor>Bebora LC</RefAuthor> <RefAuthor>Nyaga PN</RefAuthor> <RefAuthor>Minga U</RefAuthor> <RefAuthor>Olsen JE</RefAuthor> <RefTitle>Sensitivity of Listeria species, recovered from indigenous chickens to antibiotics and disinfectants</RefTitle> <RefYear>2004</RefYear> <RefJournal>East Afr Med J</RefJournal> <RefPage>534-7</RefPage> <RefTotal>Njagi LW, Mbuthia PG, Bebora LC, Nyaga PN, Minga U, Olsen JE. Sensitivity of Listeria species, recovered from indigenous chickens to antibiotics and disinfectants. East Afr Med J. 2004 Oct;81(10):534-7. DOI: 10.4314&#47;eamj.v81i10.9237</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.4314&#47;eamj.v81i10.9237</RefLink> </Reference> <Reference refNo="29"> <RefAuthor>Hakenbeck R</RefAuthor> <RefAuthor>Hof H</RefAuthor> <RefTitle>Relatedness of penicillin-binding proteins from various Listeria species</RefTitle> <RefYear>1991</RefYear> <RefJournal>FEMS Microbiol Lett</RefJournal> <RefPage>191-5</RefPage> <RefTotal>Hakenbeck R, Hof H. Relatedness of penicillin-binding proteins from various Listeria species. FEMS Microbiol Lett. 1991 Nov;68(2):191-5. DOI: 10.1111&#47;j.1574-6968.1991.tb04595.x</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1111&#47;j.1574-6968.1991.tb04595.x</RefLink> </Reference> <Reference refNo="30"> <RefAuthor>Korsak D</RefAuthor> <RefAuthor>Markiewicz Z</RefAuthor> <RefAuthor>Gutkind GO</RefAuthor> <RefAuthor>Ayala JA</RefAuthor> <RefTitle>Identification of the full set of Listeria monocytogenes penicillin-binding proteins and characterization of PBPD2 (Lmo2812)</RefTitle> <RefYear>2010</RefYear> <RefJournal>BMC Microbiol</RefJournal> <RefPage>239</RefPage> <RefTotal>Korsak D, Markiewicz Z, Gutkind GO, Ayala JA. Identification of the full set of Listeria monocytogenes penicillin-binding proteins and characterization of PBPD2 (Lmo2812). BMC Microbiol. 2010;10:239. DOI: 10.1186&#47;1471-2180-10-239</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1186&#47;1471-2180-10-239</RefLink> </Reference> <Reference refNo="31"> <RefAuthor>Hof H</RefAuthor> <RefTitle>Listeriosis: therapeutic options</RefTitle> <RefYear>2003</RefYear> <RefJournal>FEMS Immunol Med Microbiol</RefJournal> <RefPage>203-5</RefPage> <RefTotal>Hof H. Listeriosis: therapeutic options. FEMS Immunol Med Microbiol. 2003 Apr;35(3):203-5. DOI: 10.1016&#47;S0928-8244(02)00466-2</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1016&#47;S0928-8244(02)00466-2</RefLink> </Reference> <Reference refNo="32"> <RefAuthor>G&#252;ckl H</RefAuthor> <RefAuthor>Hof H</RefAuthor> <RefTitle>Vergleich der therapeutischen Wirkung von verschiedenen Penicillinderivaten und Imipenem bei der experimentellen Listeriose</RefTitle> <RefYear>1986</RefYear> <RefJournal>Z antimikrob antineoplast Chemother</RefJournal> <RefPage>83-7</RefPage> <RefTotal>G&#252;ckl H, Hof H. Vergleich der therapeutischen Wirkung von verschiedenen Penicillinderivaten und Imipenem bei der experimentellen Listeriose. Z antimikrob antineoplast Chemother. 1986;4:83-7.</RefTotal> </Reference> <Reference refNo="33"> <RefAuthor>Nichterlein T</RefAuthor> <RefAuthor>Domann E</RefAuthor> <RefAuthor>Kretschmar M</RefAuthor> <RefAuthor>Bauer M</RefAuthor> <RefAuthor>Hlawatsch A</RefAuthor> <RefAuthor>Hof H</RefAuthor> <RefAuthor>Chakraborty T</RefAuthor> <RefTitle>Subinhibitory concentrations of beta-lactams and other cell-wall antibiotics inhibit listeriolysin production by Listeria monocytogenes</RefTitle> <RefYear>1996</RefYear> <RefJournal>Int J Antimicrob Agents</RefJournal> <RefPage>75-81</RefPage> <RefTotal>Nichterlein T, Domann E, Kretschmar M, Bauer M, Hlawatsch A, Hof H, Chakraborty T. Subinhibitory concentrations of beta-lactams and other cell-wall antibiotics inhibit listeriolysin production by Listeria monocytogenes. Int J Antimicrob Agents. 1996 May;7(1):75-81. </RefTotal> </Reference> <Reference refNo="34"> <RefAuthor>Hof H</RefAuthor> <RefAuthor>Zinn U</RefAuthor> <RefAuthor>Str&#246;der J</RefAuthor> <RefTitle>Die Wirkung von Chinolinderivaten auf Listerien</RefTitle> <RefYear>1985</RefYear> <RefJournal>Z antimikrob antineoplast Chemother</RefJournal> <RefPage>115-20</RefPage> <RefTotal>Hof H, Zinn U, Str&#246;der J. Die Wirkung von Chinolinderivaten auf Listerien. Z antimikrob antineoplast Chemother. 1985;3:115-20.</RefTotal> </Reference> <Reference refNo="35"> <RefAuthor>Lampidis R</RefAuthor> <RefAuthor>Kostrewa D</RefAuthor> <RefAuthor>Hof H</RefAuthor> <RefTitle>Molecular characterization of the genes encoding DNA gyrase and topoisomerase IV of Listeria monocytogenes</RefTitle> <RefYear>2002</RefYear> <RefJournal>J Antimicrob Chemother</RefJournal> <RefPage>917-24</RefPage> <RefTotal>Lampidis R, Kostrewa D, Hof H. Molecular characterization of the genes encoding DNA gyrase and topoisomerase IV of Listeria monocytogenes. J Antimicrob Chemother. 2002 Jun;49(6):917-24. DOI: 10.1093&#47;jac&#47;dkf065</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1093&#47;jac&#47;dkf065</RefLink> </Reference> <Reference refNo="36"> <RefAuthor>Hof H</RefAuthor> <RefAuthor>Fabrig J</RefAuthor> <RefTitle>Die Wirkung von Gyrase-Hemmern auf Listerien</RefTitle> <RefYear>1987</RefYear> <RefJournal>Fortschr antimicrob antineoplast Chemother</RefJournal> <RefPage>1781-5</RefPage> <RefTotal>Hof H, Fabrig J. Die Wirkung von Gyrase-Hemmern auf Listerien. Fortschr antimicrob antineoplast Chemother. 1987;6-10:1781-5.</RefTotal> </Reference> <Reference refNo="37"> <RefAuthor>Nichterlein T</RefAuthor> <RefAuthor>Bornitz F</RefAuthor> <RefAuthor>Kretschmar M</RefAuthor> <RefAuthor>Hof H</RefAuthor> <RefTitle>Clinafloxacin (CL 960) is superior to standard therapeutics in the treatment of murine listeriosis and salmonellosis</RefTitle> <RefYear>1997</RefYear> <RefJournal>Zentralbl Bakteriol</RefJournal> <RefPage>401-12</RefPage> <RefTotal>Nichterlein T, Bornitz F, Kretschmar M, Hof H. Clinafloxacin (CL 960) is superior to standard therapeutics in the treatment of murine listeriosis and salmonellosis. Zentralbl Bakteriol. 1997 Oct;286(3):401-12. </RefTotal> </Reference> <Reference refNo="38"> <RefAuthor>Nichterlein T</RefAuthor> <RefAuthor>Bornitz F</RefAuthor> <RefAuthor>Kretschmar M</RefAuthor> <RefAuthor></RefAuthor> <RefTitle>The activity of moxifloxacin, a new 8-methoxyquinolone, against strains of salmonellae and Listeria monocytogens in vitro, in mouse infections and in infected tissue cells</RefTitle> <RefYear>1999</RefYear> <RefBookTitle>Moxifloxacin in practice. Vol. 2</RefBookTitle> <RefPage>71-82</RefPage> <RefTotal>Nichterlein T, Bornitz F, Kretschmar M, et al. The activity of moxifloxacin, a new 8-methoxyquinolone, against strains of salmonellae and Listeria monocytogens in vitro, in mouse infections and in infected tissue cells. In: Adam D, Finch R, editors. Moxifloxacin in practice. Vol. 2. Oxford: Maxim Medical; 1999. p. 71-82.</RefTotal> </Reference> <Reference refNo="39"> <RefAuthor>Hof H</RefAuthor> <RefTitle>The effect of coumermycin on experimental listeriosis</RefTitle> <RefYear>1986</RefYear> <RefJournal>J Infect</RefJournal> <RefPage>17-23</RefPage> <RefTotal>Hof H. The effect of coumermycin on experimental listeriosis. J Infect. 1986 Jul;13(1):17-23. DOI: 10.1016&#47;S0163-4453(86)92141-9</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1016&#47;S0163-4453(86)92141-9</RefLink> </Reference> <Reference refNo="40"> <RefAuthor>Nichterlein T</RefAuthor> <RefAuthor>Hof H</RefAuthor> <RefTitle>Effect of various antibiotics on Listeria monocytogenes multiplying in L 929 cells</RefTitle> <RefYear>1991</RefYear> <RefJournal>Infection</RefJournal> <RefPage>S234-8</RefPage> <RefTotal>Nichterlein T, Hof H. Effect of various antibiotics on Listeria monocytogenes multiplying in L 929 cells. Infection. 1991;19 Suppl 4:S234-8. DOI: 10.1007&#47;BF01644040</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1007&#47;BF01644040</RefLink> </Reference> <Reference refNo="41"> <RefAuthor>Emmerling P</RefAuthor> <RefAuthor>Schr&#246;ter G</RefAuthor> <RefAuthor>Hof H</RefAuthor> <RefTitle>Listeriose. Klinik, Epidemiologie, Pathogenese, Infektabwehr und Chemotherapie</RefTitle> <RefYear>1985</RefYear> <RefJournal>Med Welt</RefJournal> <RefPage>1517-21</RefPage> <RefTotal>Emmerling P, Schr&#246;ter G, Hof H. Listeriose. Klinik, Epidemiologie, Pathogenese, Infektabwehr und Chemotherapie. Med Welt. 1985;35:1517-21.</RefTotal> </Reference> <Reference refNo="42"> <RefAuthor>Nichterlein T</RefAuthor> <RefAuthor>Domann E</RefAuthor> <RefAuthor>Bauer M</RefAuthor> <RefAuthor>Hlawatsch A</RefAuthor> <RefAuthor>Kretschmar M</RefAuthor> <RefAuthor>Chakraborty T</RefAuthor> <RefAuthor>Hof H</RefAuthor> <RefTitle>Subinhibitory concentrations of gentamicin reduce production of listeriolysin, the main virulence factor of Listeria monocytogenes</RefTitle> <RefYear>1997</RefYear> <RefJournal>Clin Microbiol Infect</RefJournal> <RefPage>270-272</RefPage> <RefTotal>Nichterlein T, Domann E, Bauer M, Hlawatsch A, Kretschmar M, Chakraborty T, Hof H. Subinhibitory concentrations of gentamicin reduce production of listeriolysin, the main virulence factor of Listeria monocytogenes. Clin Microbiol Infect. 1997 Apr;3(2):270-272.</RefTotal> </Reference> <Reference refNo="43"> <RefAuthor>Hof H</RefAuthor> <RefTitle>Antibiotic treatment of infections with intracellular bacteria</RefTitle> <RefYear>1999</RefYear> <RefBookTitle>Opportunistic intracellular bacteria and immunity</RefBookTitle> <RefPage>281-93</RefPage> <RefTotal>Hof H. Antibiotic treatment of infections with intracellular bacteria. In: Paradise L, Friedman H, Bendinelli M, editors. Opportunistic intracellular bacteria and immunity. New York: Plenum Press; 1999. (Infectious Agents and Pathogenesis). p. 281-93.</RefTotal> </Reference> <Reference refNo="44"> <RefAuthor>Michelet C</RefAuthor> <RefAuthor>Avril JL</RefAuthor> <RefAuthor>Cartier F</RefAuthor> <RefAuthor>Berche P</RefAuthor> <RefTitle>Inhibition of intracellular growth of Listeria monocytogenes by antibiotics</RefTitle> <RefYear>1994</RefYear> <RefJournal>Antimicrob Agents Chemother</RefJournal> <RefPage>438-46</RefPage> <RefTotal>Michelet C, Avril JL, Cartier F, Berche P. Inhibition of intracellular growth of Listeria monocytogenes by antibiotics. Antimicrob Agents Chemother. 1994 Mar;38(3):438-46. DOI: 10.1128&#47;AAC.38.3.438</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1128&#47;AAC.38.3.438</RefLink> </Reference> <Reference refNo="45"> <RefAuthor>Scortti M</RefAuthor> <RefAuthor>Lacharme-Lora L</RefAuthor> <RefAuthor>Wagner M</RefAuthor> <RefAuthor>Chico-Calero I</RefAuthor> <RefAuthor>Losito P</RefAuthor> <RefAuthor>V&#225;zquez-Boland JA</RefAuthor> <RefTitle>Coexpression of virulence and fosfomycin susceptibility in Listeria: molecular basis of an antimicrobial in vitro-in vivo paradox</RefTitle> <RefYear>2006</RefYear> <RefJournal>Nat Med</RefJournal> <RefPage>515-7</RefPage> <RefTotal>Scortti M, Lacharme-Lora L, Wagner M, Chico-Calero I, Losito P, V&#225;zquez-Boland JA. Coexpression of virulence and fosfomycin susceptibility in Listeria: molecular basis of an antimicrobial in vitro-in vivo paradox. Nat Med. 2006 May;12(5):515-7. DOI: 10.1038&#47;nm1396</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1038&#47;nm1396</RefLink> </Reference> <Reference refNo="46"> <RefAuthor>Fillgrove KL</RefAuthor> <RefAuthor>Pakhomova S</RefAuthor> <RefAuthor>Schaab MR</RefAuthor> <RefAuthor>Newcomer ME</RefAuthor> <RefAuthor>Armstrong RN</RefAuthor> <RefTitle>Structure and mechanism of the genomically encoded fosfomycin resistance protein, FosX, from Listeria monocytogenes</RefTitle> <RefYear>2007</RefYear> <RefJournal>Biochemistry</RefJournal> <RefPage>8110-20</RefPage> <RefTotal>Fillgrove KL, Pakhomova S, Schaab MR, Newcomer ME, Armstrong RN. Structure and mechanism of the genomically encoded fosfomycin resistance protein, FosX, from Listeria monocytogenes. Biochemistry. 2007 Jul;46(27):8110-20. DOI: 10.1021&#47;bi700625p</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1021&#47;bi700625p</RefLink> </Reference> <Reference refNo="47"> <RefAuthor>Carryn S</RefAuthor> <RefAuthor>Van Bambeke F</RefAuthor> <RefAuthor>Mingeot-Leclercq MP</RefAuthor> <RefAuthor>Tulkens PM</RefAuthor> <RefTitle>Activity of beta-lactams (ampicillin, meropenem), gentamicin, azithromycin and moxifloxacin against intracellular Listeria monocytogenes in a 24 h THP-1 human macrophage model</RefTitle> <RefYear>2003</RefYear> <RefJournal>J Antimicrob Chemother</RefJournal> <RefPage>1051-2</RefPage> <RefTotal>Carryn S, Van Bambeke F, Mingeot-Leclercq MP, Tulkens PM. Activity of beta-lactams (ampicillin, meropenem), gentamicin, azithromycin and moxifloxacin against intracellular Listeria monocytogenes in a 24 h THP-1 human macrophage model. J Antimicrob Chemother. 2003 Apr;51(4):1051-2. DOI: 10.1093&#47;jac&#47;dkg189</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1093&#47;jac&#47;dkg189</RefLink> </Reference> <Reference refNo="48"> <RefAuthor>Emmerling P</RefAuthor> <RefAuthor>Hof H</RefAuthor> <RefAuthor>Finger H</RefAuthor> <RefTitle>Infektabwehr von Listeria monocytogenes bei normalen und immundefekten M&#228;usen unter Ampicillintherapie</RefTitle> <RefYear>1978</RefYear> <RefJournal>Zentralbl Bakteriol Orig A</RefJournal> <RefPage>339-46</RefPage> <RefTotal>Emmerling P, Hof H, Finger H. Infektabwehr von Listeria monocytogenes bei normalen und immundefekten M&#228;usen unter Ampicillintherapie &#91;Resistance to infection with Listeria monocytogenes in normal and thymusless mice treated with ampicillin&#93;. Zentralbl Bakteriol Orig A. 1978 Apr;240(3):339-46.</RefTotal> </Reference> <Reference refNo="49"> <RefAuthor>Sauer JD</RefAuthor> <RefAuthor>Witte CE</RefAuthor> <RefAuthor>Zemansky J</RefAuthor> <RefAuthor>Hanson B</RefAuthor> <RefAuthor>Lauer P</RefAuthor> <RefAuthor>Portnoy DA</RefAuthor> <RefTitle>Listeria monocytogenes triggers AIM2-mediated pyroptosis upon infrequent bacteriolysis in the macrophage cytosol</RefTitle> <RefYear>2010</RefYear> <RefJournal>Cell Host Microbe</RefJournal> <RefPage>412-9</RefPage> <RefTotal>Sauer JD, Witte CE, Zemansky J, Hanson B, Lauer P, Portnoy DA. Listeria monocytogenes triggers AIM2-mediated pyroptosis upon infrequent bacteriolysis in the macrophage cytosol. Cell Host Microbe. 2010 May;7(5):412-9. DOI: 10.1016&#47;j.chom.2010.04.004</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1016&#47;j.chom.2010.04.004</RefLink> </Reference> <Reference refNo="50"> <RefAuthor>Marquez B</RefAuthor> <RefAuthor>Caceres NE</RefAuthor> <RefAuthor>Mingeot-Leclercq MP</RefAuthor> <RefAuthor>Tulkens PM</RefAuthor> <RefAuthor>Van Bambeke F</RefAuthor> <RefTitle>Identification of the efflux transporter of the fluoroquinolone antibiotic ciprofloxacin in murine macrophages: studies with ciprofloxacin-resistant cells</RefTitle> <RefYear>2009</RefYear> <RefJournal>Antimicrob Agents Chemother</RefJournal> <RefPage>2410-6</RefPage> <RefTotal>Marquez B, Caceres NE, Mingeot-Leclercq MP, Tulkens PM, Van Bambeke F. Identification of the efflux transporter of the fluoroquinolone antibiotic ciprofloxacin in murine macrophages: studies with ciprofloxacin-resistant cells. Antimicrob Agents Chemother. 2009 Jun;53(6):2410-6. DOI: 10.1128&#47;AAC.01428-08</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1128&#47;AAC.01428-08</RefLink> </Reference> <Reference refNo="51"> <RefAuthor>Grayo S</RefAuthor> <RefAuthor>Join-Lambert O</RefAuthor> <RefAuthor>Desroches MC</RefAuthor> <RefAuthor>Le Monnier A</RefAuthor> <RefTitle>Comparison of the in vitro efficacies of moxifloxacin and amoxicillin against Listeria monocytogenes</RefTitle> <RefYear>2008</RefYear> <RefJournal>Antimicrob Agents Chemother</RefJournal> <RefPage>1697-702</RefPage> <RefTotal>Grayo S, Join-Lambert O, Desroches MC, Le Monnier A. Comparison of the in vitro efficacies of moxifloxacin and amoxicillin against Listeria monocytogenes. Antimicrob Agents Chemother. 2008 May;52(5):1697-702. DOI: 10.1128&#47;AAC.01211-07</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1128&#47;AAC.01211-07</RefLink> </Reference> <Reference refNo="52"> <RefAuthor>Lismond A</RefAuthor> <RefAuthor>Tulkens PM</RefAuthor> <RefAuthor>Mingeot-Leclercq MP</RefAuthor> <RefAuthor>Courvalin P</RefAuthor> <RefAuthor>Van Bambeke F</RefAuthor> <RefTitle>Cooperation between prokaryotic (Lde) and eukaryotic (MRP) efflux transporters in J774 macrophages infected with Listeria monocytogenes: studies with ciprofloxacin and moxifloxacin</RefTitle> <RefYear>2008</RefYear> <RefJournal>Antimicrob Agents Chemother</RefJournal> <RefPage>3040-6</RefPage> <RefTotal>Lismond A, Tulkens PM, Mingeot-Leclercq MP, Courvalin P, Van Bambeke F. Cooperation between prokaryotic (Lde) and eukaryotic (MRP) efflux transporters in J774 macrophages infected with Listeria monocytogenes: studies with ciprofloxacin and moxifloxacin. Antimicrob Agents Chemother. 2008 Sep;52(9):3040-6. DOI: 10.1128&#47;AAC.00105-08</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1128&#47;AAC.00105-08</RefLink> </Reference> <Reference refNo="53"> <RefAuthor>Grayo S</RefAuthor> <RefAuthor>Lott-Desroches MC</RefAuthor> <RefAuthor>Dussurget O</RefAuthor> <RefAuthor>Respaud R</RefAuthor> <RefAuthor>Fontanet A</RefAuthor> <RefAuthor>Join-Lambert O</RefAuthor> <RefAuthor>Singlas E</RefAuthor> <RefAuthor>Le Monnier A</RefAuthor> <RefTitle>Rapid eradication of Listeria monocytogenes by moxifloxacin in a murine model of central nervous system listeriosis</RefTitle> <RefYear>2008</RefYear> <RefJournal>Antimicrob Agents Chemother</RefJournal> <RefPage>3210-5</RefPage> <RefTotal>Grayo S, Lott-Desroches MC, Dussurget O, Respaud R, Fontanet A, Join-Lambert O, Singlas E, Le Monnier A. Rapid eradication of Listeria monocytogenes by moxifloxacin in a murine model of central nervous system listeriosis. Antimicrob Agents Chemother. 2008 Sep;52(9):3210-5. DOI: 10.1128&#47;AAC.00177-08</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1128&#47;AAC.00177-08</RefLink> </Reference> <Reference refNo="54"> <RefAuthor>Sipahi OR</RefAuthor> <RefAuthor>Turhan T</RefAuthor> <RefAuthor>Pullukcu H</RefAuthor> <RefAuthor>Calik S</RefAuthor> <RefAuthor>Tasbakan M</RefAuthor> <RefAuthor>Sipahi H</RefAuthor> <RefAuthor>Arda B</RefAuthor> <RefAuthor>Yamazhan T</RefAuthor> <RefAuthor>Ulusoy S</RefAuthor> <RefTitle>Moxifloxacin versus ampicillin &#43; gentamicin in the therapy of experimental Listeria monocytogenes meningitis</RefTitle> <RefYear>2008</RefYear> <RefJournal>J Antimicrob Chemother</RefJournal> <RefPage>670-3</RefPage> <RefTotal>Sipahi OR, Turhan T, Pullukcu H, Calik S, Tasbakan M, Sipahi H, Arda B, Yamazhan T, Ulusoy S. Moxifloxacin versus ampicillin &#43; gentamicin in the therapy of experimental Listeria monocytogenes meningitis. J Antimicrob Chemother. 2008 Mar;61(3):670-3. DOI: 10.1093&#47;jac&#47;dkn001</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1093&#47;jac&#47;dkn001</RefLink> </Reference> <Reference refNo="55"> <RefAuthor>Hof H</RefAuthor> <RefAuthor>Waldenmeier G</RefAuthor> <RefTitle>Therapy of experimental listeriosis--an evaluation of different antibiotics</RefTitle> <RefYear>1988</RefYear> <RefJournal>Infection</RefJournal> <RefPage>S171-4</RefPage> <RefTotal>Hof H, Waldenmeier G. Therapy of experimental listeriosis--an evaluation of different antibiotics. Infection. 1988;16 Suppl 2:S171-4. DOI: 10.1007&#47;BF01639743</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1007&#47;BF01639743</RefLink> </Reference> <Reference refNo="56"> <RefAuthor>Strauss R</RefAuthor> <RefAuthor>Hof H</RefAuthor> <RefAuthor>Str&#246;der J</RefAuthor> <RefTitle>Antibiotikatherapie im abwehrgeschw&#228;chten Wirt &#8211; dargestellt am Modell der Listeriose der Maus: Die Wirkung von Erythromycin, anderen Makrolidantibiotika und verwandten Antibiotika</RefTitle> <RefYear>1985</RefYear> <RefJournal>Z antimikrob antineoplast Chemother</RefJournal> <RefPage>107-14</RefPage> <RefTotal>Strauss R, Hof H, Str&#246;der J. Antibiotikatherapie im abwehrgeschw&#228;chten Wirt &#8211; dargestellt am Modell der Listeriose der Maus: Die Wirkung von Erythromycin, anderen Makrolidantibiotika und verwandten Antibiotika. Z antimikrob antineoplast Chemother. 1985;3:107-14.</RefTotal> </Reference> <Reference refNo="57"> <RefAuthor>Siebor E</RefAuthor> <RefAuthor>Kazmierczak A</RefAuthor> <RefTitle>Factors influencing the activity of macrolide antibiotics in vitro</RefTitle> <RefYear>1993</RefYear> <RefBookTitle>Macrolides. Chemistry, pharmacology and clinical use</RefBookTitle> <RefPage>197-203</RefPage> <RefTotal>Siebor E, Kazmierczak A. Factors influencing the activity of macrolide antibiotics in vitro. In: Bryskier AJ, Butzler JP, Neu HC, Tulkens PM, editors. Macrolides. Chemistry, pharmacology and clinical use. Paris: Arnette Blackwell; 1993. p. 197-203.</RefTotal> </Reference> <Reference refNo="58"> <RefAuthor>Hof H</RefAuthor> <RefAuthor>Kuhn B</RefAuthor> <RefTitle>Antibiotikatherapie im abwehrgeschw&#228;chten Wirtdargestellt am Modell der Listeriose der Maus. II. Die Wirkung von Tetrazyklin</RefTitle> <RefYear>1983</RefYear> <RefJournal>Immun Infekt</RefJournal> <RefPage>61-4</RefPage> <RefTotal>Hof H, Kuhn B. Antibiotikatherapie im abwehrgeschw&#228;chten Wirtdargestellt am Modell der Listeriose der Maus. II. Die Wirkung von Tetrazyklin &#91;Antibiotic therapy in the compromised host--presented as a model for listeriosis in the mouse. II. Effect of tetracycline&#93;. Immun Infekt. 1983 Mar;11(2):61-4.</RefTotal> </Reference> <Reference refNo="59"> <RefAuthor>Kawaler B</RefAuthor> <RefAuthor>Hof H</RefAuthor> <RefTitle>Murine model for therapy of listeriosis in the compromised host. IV. Cotrimoxazole</RefTitle> <RefYear>1985</RefYear> <RefJournal>Chemotherapy</RefJournal> <RefPage>366-71</RefPage> <RefTotal>Kawaler B, Hof H. Murine model for therapy of listeriosis in the compromised host. IV. Cotrimoxazole. Chemotherapy. 1985;31(5):366-71.</RefTotal> </Reference> <Reference refNo="60"> <RefAuthor>Hof H</RefAuthor> <RefAuthor>G&#252;ckel H</RefAuthor> <RefTitle>Lack of synergism of ampicillin and gentamicin in experimental listeriosis</RefTitle> <RefYear>1987</RefYear> <RefJournal>Infection</RefJournal> <RefPage>40-1</RefPage> <RefTotal>Hof H, G&#252;ckel H. Lack of synergism of ampicillin and gentamicin in experimental listeriosis. Infection. 1987 Jan-Feb;15(1):40-1. DOI: 10.1007&#47;BF01646117</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1007&#47;BF01646117</RefLink> </Reference> <Reference refNo="61"> <RefAuthor>Tuazon CU</RefAuthor> <RefAuthor>Shamsuddin D</RefAuthor> <RefAuthor>Miller H</RefAuthor> <RefTitle>Antibiotic susceptibility and synergy of clinical isolates of Listeria monocytogenes</RefTitle> <RefYear>1982</RefYear> <RefJournal>Antimicrob Agents Chemother</RefJournal> <RefPage>525-7</RefPage> <RefTotal>Tuazon CU, Shamsuddin D, Miller H. Antibiotic susceptibility and synergy of clinical isolates of Listeria monocytogenes. Antimicrob Agents Chemother. 1982 Mar;21(3):525-7. DOI: 10.1128&#47;AAC.21.3.525</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1128&#47;AAC.21.3.525</RefLink> </Reference> <Reference refNo="62"> <RefAuthor>Vischer WA</RefAuthor> <RefAuthor>Rominger C</RefAuthor> <RefTitle>Rifampicin against experimental listeriosis in the mouse</RefTitle> <RefYear>1978</RefYear> <RefJournal>Chemotherapy</RefJournal> <RefPage>104-11</RefPage> <RefTotal>Vischer WA, Rominger C. Rifampicin against experimental listeriosis in the mouse. Chemotherapy. 1978;24(2):104-11. DOI: 10.1159&#47;000237768</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1159&#47;000237768</RefLink> </Reference> <Reference refNo="63"> <RefAuthor>Hof H</RefAuthor> <RefAuthor>Emmerling P</RefAuthor> <RefTitle>Murine model for therapy of listeriosis in the compromised host. III. The effect of rifampicin</RefTitle> <RefYear>1984</RefYear> <RefJournal>Chemotherapy</RefJournal> <RefPage>125-30</RefPage> <RefTotal>Hof H, Emmerling P. Murine model for therapy of listeriosis in the compromised host. III. The effect of rifampicin. Chemotherapy. 1984;30(2):125-30. DOI: 10.1159&#47;000238258</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1159&#47;000238258</RefLink> </Reference> <Reference refNo="64"> <RefAuthor>Scheld WM</RefAuthor> <RefAuthor>Fletcher DD</RefAuthor> <RefAuthor>Fink FN</RefAuthor> <RefAuthor>Sande MA</RefAuthor> <RefTitle>Response to therapy in an experimental rabbit model of meningitis due to Listeria monocytogenes</RefTitle> <RefYear>1979</RefYear> <RefJournal>J Infect Dis</RefJournal> <RefPage>287-94</RefPage> <RefTotal>Scheld WM, Fletcher DD, Fink FN, Sande MA. Response to therapy in an experimental rabbit model of meningitis due to Listeria monocytogenes. J Infect Dis. 1979 Sep;140(3):287-94. DOI: 10.1093&#47;infdis&#47;140.3.287</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1093&#47;infdis&#47;140.3.287</RefLink> </Reference> <Reference refNo="65"> <RefAuthor>Berner R</RefAuthor> <RefAuthor>Hof H</RefAuthor> <RefTitle>Therapeutic activity of teicoplanin on experimental listeriosis compared with that of vancomycin and ampicillin</RefTitle> <RefYear>1988</RefYear> <RefJournal>Zentralbl Bakteriol Mikrobiol Hyg A</RefJournal> <RefPage>50-6</RefPage> <RefTotal>Berner R, Hof H. Therapeutic activity of teicoplanin on experimental listeriosis compared with that of vancomycin and ampicillin. Zentralbl Bakteriol Mikrobiol Hyg A. 1988 Mar;268(1):50-6.</RefTotal> </Reference> <Reference refNo="66"> <RefAuthor>Hof H</RefAuthor> <RefTitle>Die Wirksamkeit von Daptomycin (LY 146032) auf Listerien in vitro und in vivo</RefTitle> <RefYear>1989</RefYear> <RefJournal>Z antimicrob antineoplast Chemother</RefJournal> <RefPage>35-8</RefPage> <RefTotal>Hof H. Die Wirksamkeit von Daptomycin (LY 146032) auf Listerien in vitro und in vivo. Z antimicrob antineoplast Chemother. 1989;7:35-8.</RefTotal> </Reference> <Reference refNo="67"> <RefAuthor>Salimnia H</RefAuthor> <RefAuthor>Patel D</RefAuthor> <RefAuthor>Lephart PR</RefAuthor> <RefAuthor>Fairfax MR</RefAuthor> <RefAuthor>Chandrasekar PH</RefAuthor> <RefTitle>Listeria grayi: vancomycin-resistant, gram-positive rod causing bacteremia in a stem cell transplant recipient</RefTitle> <RefYear>2010</RefYear> <RefJournal>Transpl Infect Dis</RefJournal> <RefPage>526-8</RefPage> <RefTotal>Salimnia H, Patel D, Lephart PR, Fairfax MR, Chandrasekar PH. Listeria grayi: vancomycin-resistant, gram-positive rod causing bacteremia in a stem cell transplant recipient. Transpl Infect Dis. 2010 Dec;12(6):526-8. DOI: 10.1111&#47;j.1399-3062.2010.00539.x</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1111&#47;j.1399-3062.2010.00539.x</RefLink> </Reference> <Reference refNo="68"> <RefAuthor>Callapina M</RefAuthor> <RefAuthor>Kretschmar M</RefAuthor> <RefAuthor>Dietz A</RefAuthor> <RefAuthor>Mosbach C</RefAuthor> <RefAuthor>Hof H</RefAuthor> <RefAuthor>Nichterlein T</RefAuthor> <RefTitle>Systemic and intracerebral infections of mice with Listeria monocytogenes successfully treated with linezolid</RefTitle> <RefYear>2001</RefYear> <RefJournal>J Chemother</RefJournal> <RefPage>265-9</RefPage> <RefTotal>Callapina M, Kretschmar M, Dietz A, Mosbach C, Hof H, Nichterlein T. Systemic and intracerebral infections of mice with Listeria monocytogenes successfully treated with linezolid. J Chemother. 2001 Jun;13(3):265-9.</RefTotal> </Reference> <Reference refNo="69"> <RefAuthor>Manfredi R</RefAuthor> <RefTitle>Linezolid activity against disseminated Listeria monocytogenes meningitis and central nervous system abscesses: focus on early drug myelotoxicity</RefTitle> <RefYear>2007</RefYear> <RefJournal>Curr Drug Saf</RefJournal> <RefPage>141-5</RefPage> <RefTotal>Manfredi R. Linezolid activity against disseminated Listeria monocytogenes meningitis and central nervous system abscesses: focus on early drug myelotoxicity. Curr Drug Saf. 2007 May;2(2):141-5. DOI: 10.2174&#47;157488607780598304</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.2174&#47;157488607780598304</RefLink> </Reference> <Reference refNo="70"> <RefAuthor>Myrianthefs P</RefAuthor> <RefAuthor>Markantonis SL</RefAuthor> <RefAuthor>Vlachos K</RefAuthor> <RefAuthor>Anagnostaki M</RefAuthor> <RefAuthor>Boutzouka E</RefAuthor> <RefAuthor>Panidis D</RefAuthor> <RefAuthor>Baltopoulos G</RefAuthor> <RefTitle>Serum and cerebrospinal fluid concentrations of linezolid in neurosurgical patients</RefTitle> <RefYear>2006</RefYear> <RefJournal>Antimicrob Agents Chemother</RefJournal> <RefPage>3971-6</RefPage> <RefTotal>Myrianthefs P, Markantonis SL, Vlachos K, Anagnostaki M, Boutzouka E, Panidis D, Baltopoulos G. Serum and cerebrospinal fluid concentrations of linezolid in neurosurgical patients. Antimicrob Agents Chemother. 2006 Dec;50(12):3971-6. DOI: 10.1128&#47;AAC.00051-06</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1128&#47;AAC.00051-06</RefLink> </Reference> <Reference refNo="71"> <RefAuthor>Dutta NK</RefAuthor> <RefAuthor>Mazumdar K</RefAuthor> <RefAuthor>Park JH</RefAuthor> <RefTitle>In vitro synergistic effect of gentamicin with the anti-inflammatory agent diclofenac against Listeria monocytogenes</RefTitle> <RefYear>2009</RefYear> <RefJournal>Lett Appl Microbiol</RefJournal> <RefPage>783-5</RefPage> <RefTotal>Dutta NK, Mazumdar K, Park JH. In vitro synergistic effect of gentamicin with the anti-inflammatory agent diclofenac against Listeria monocytogenes. Lett Appl Microbiol. 2009 Jun;48(6):783-5. DOI: 10.1111&#47;j.1472-765X.2009.02588.x</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1111&#47;j.1472-765X.2009.02588.x</RefLink> </Reference> <Reference refNo="72"> <RefAuthor>Lutsar I</RefAuthor> <RefAuthor>McCracken GH Jr</RefAuthor> <RefAuthor>Friedland IR</RefAuthor> <RefTitle>Antibiotic pharmacodynamics in cerebrospinal fluid</RefTitle> <RefYear>1998</RefYear> <RefJournal>Clin Infect Dis</RefJournal> <RefPage>1117-27</RefPage> <RefTotal>Lutsar I, McCracken GH Jr,Friedland IR. Antibiotic pharmacodynamics in cerebrospinal fluid. Clin Infect Dis. 1998 Nov;27(5):1117-27. DOI: 10.1086&#47;515003</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1086&#47;515003</RefLink> </Reference> <Reference refNo="73"> <RefAuthor>Kanellakopoulou K</RefAuthor> <RefAuthor>Pagoulatou A</RefAuthor> <RefAuthor>Stroumpoulis K</RefAuthor> <RefAuthor>Vafiadou M</RefAuthor> <RefAuthor>Kranidioti H</RefAuthor> <RefAuthor>Giamarellou H</RefAuthor> <RefAuthor>Giamarellos-Bourboulis EJ</RefAuthor> <RefTitle>Pharmacokinetics of moxifloxacin in non-inflamed cerebrospinal fluid of humans: implication for a bactericidal effect</RefTitle> <RefYear>2008</RefYear> <RefJournal>J Antimicrob Chemother</RefJournal> <RefPage>1328-31</RefPage> <RefTotal>Kanellakopoulou K, Pagoulatou A, Stroumpoulis K, Vafiadou M, Kranidioti H, Giamarellou H, Giamarellos-Bourboulis EJ. Pharmacokinetics of moxifloxacin in non-inflamed cerebrospinal fluid of humans: implication for a bactericidal effect. J Antimicrob Chemother. 2008 Jun;61(6):1328-31. DOI: 10.1093&#47;jac&#47;dkn110</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1093&#47;jac&#47;dkn110</RefLink> </Reference> <Reference refNo="74"> <RefAuthor>Hou JP</RefAuthor> <RefAuthor>Poole JW</RefAuthor> <RefTitle>Kinetics and mechanism of degradation of ampicillin in solution</RefTitle> <RefYear>1969</RefYear> <RefJournal>J Pharm Sci</RefJournal> <RefPage>447-54</RefPage> <RefTotal>Hou JP, Poole JW. Kinetics and mechanism of degradation of ampicillin in solution. J Pharm Sci. 1969 Apr;58(4):447-54. DOI: 10.1002&#47;jps.2600580412</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1002&#47;jps.2600580412</RefLink> </Reference> <Reference refNo="75"> <RefAuthor>Jerzsele A</RefAuthor> <RefAuthor>Nagy G</RefAuthor> <RefTitle>The stability of amoxicillin trihydrate and potassium clavulanate combination in aqueous solutions</RefTitle> <RefYear>2009</RefYear> <RefJournal>Acta Vet Hung</RefJournal> <RefPage>485-93</RefPage> <RefTotal>Jerzsele A, Nagy G. The stability of amoxicillin trihydrate and potassium clavulanate combination in aqueous solutions. Acta Vet Hung. 2009 Dec;57(4):485-93. DOI: 10.1556&#47;AVet.57.2009.4.3</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1556&#47;AVet.57.2009.4.3</RefLink> </Reference> <Reference refNo="76"> <RefAuthor>Heymer B</RefAuthor> <RefAuthor>Wirsing von K&#246;nig CH</RefAuthor> <RefAuthor>Finger H</RefAuthor> <RefAuthor>Hof H</RefAuthor> <RefAuthor>Emmerling P</RefAuthor> <RefTitle>Histomorphology of experimental listeriosis</RefTitle> <RefYear>1988</RefYear> <RefJournal>Infection</RefJournal> <RefPage>S106-11</RefPage> <RefTotal>Heymer B, Wirsing von K&#246;nig CH, Finger H, Hof H, Emmerling P. Histomorphology of experimental listeriosis. Infection. 1988;16 Suppl 2:S106-11. DOI: 10.1007&#47;BF01639731</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1007&#47;BF01639731</RefLink> </Reference> <Reference refNo="77"> <RefAuthor>Pacifici GM</RefAuthor> <RefTitle>Placental transfer of antibiotics administered to the mother: a review</RefTitle> <RefYear>2006</RefYear> <RefJournal>Int J Clin Pharmacol Ther</RefJournal> <RefPage>57-63</RefPage> <RefTotal>Pacifici GM. Placental transfer of antibiotics administered to the mother: a review. Int J Clin Pharmacol Ther. 2006 Feb;44(2):57-63. DOI: 10.5414&#47;CPP44057</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.5414&#47;CPP44057</RefLink> </Reference> <Reference refNo="78"> <RefAuthor>Witt A</RefAuthor> <RefAuthor>Sommer EM</RefAuthor> <RefAuthor>Cichna M</RefAuthor> <RefAuthor>Postlbauer K</RefAuthor> <RefAuthor>Widhalm A</RefAuthor> <RefAuthor>Gregor H</RefAuthor> <RefAuthor>Reisenberger K</RefAuthor> <RefTitle>Placental passage of clarithromycin surpasses other macrolide antibiotics</RefTitle> <RefYear>2003</RefYear> <RefJournal>Am J Obstet Gynecol</RefJournal> <RefPage>816-9</RefPage> <RefTotal>Witt A, Sommer EM, Cichna M, Postlbauer K, Widhalm A, Gregor H, Reisenberger K. Placental passage of clarithromycin surpasses other macrolide antibiotics. Am J Obstet Gynecol. 2003 Mar;188(3):816-9. DOI: 10.1067&#47;mob.2003.171</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1067&#47;mob.2003.171</RefLink> </Reference> <Reference refNo="79"> <RefAuthor>Altaie R</RefAuthor> <RefAuthor>Fahy GT</RefAuthor> <RefAuthor>Cormican M</RefAuthor> <RefTitle>Failure of Listeria monocytogenes keratitis to respond to topical ofloxacin</RefTitle> <RefYear>2006</RefYear> <RefJournal>Cornea</RefJournal> <RefPage>849-50</RefPage> <RefTotal>Altaie R, Fahy GT, Cormican M. Failure of Listeria monocytogenes keratitis to respond to topical ofloxacin. Cornea. 2006 Aug;25(7):849-50. DOI: 10.1097&#47;01.ico.0000230251.19847.3a</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1097&#47;01.ico.0000230251.19847.3a</RefLink> </Reference> <Reference refNo="80"> <RefAuthor>Van den Broek PJ</RefAuthor> <RefTitle>Antibiotics and phagocytic cells</RefTitle> <RefYear>1993</RefYear> <RefBookTitle>Antimicrobial agents and intracellular pathogens</RefBookTitle> <RefPage></RefPage> <RefTotal>Van den Broek PJ. Antibiotics and phagocytic cells. In: Raoult D, editor. Antimicrobial agents and intracellular pathogens. Boca Raton: CRC Press; 1993. p 1-22.</RefTotal> </Reference> <Reference refNo="81"> <RefAuthor>Mylonakis E</RefAuthor> <RefAuthor>Hohmann EL</RefAuthor> <RefAuthor>Calderwood SB</RefAuthor> <RefTitle>Central nervous system infection with Listeria monocytogenes. 33 years&#39; experience at a general hospital and review of 776 episodes from the literature</RefTitle> <RefYear>1998</RefYear> <RefJournal>Medicine (Baltimore)</RefJournal> <RefPage>313-36</RefPage> <RefTotal>Mylonakis E, Hohmann EL, Calderwood SB. Central nervous system infection with Listeria monocytogenes. 33 years&#39; experience at a general hospital and review of 776 episodes from the literature. Medicine (Baltimore). 1998 Sep;77(5):313-36. DOI: 10.1097&#47;00005792-199809000-00002</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1097&#47;00005792-199809000-00002</RefLink> </Reference> <Reference refNo="82"> <RefAuthor>Mitj&#224; O</RefAuthor> <RefAuthor>Pigrau C</RefAuthor> <RefAuthor>Ruiz I</RefAuthor> <RefAuthor>Vidal X</RefAuthor> <RefAuthor>Almirante B</RefAuthor> <RefAuthor>Planes AM</RefAuthor> <RefAuthor>Molina I</RefAuthor> <RefAuthor>Rodr&#237;guez D</RefAuthor> <RefAuthor>Pahissa A</RefAuthor> <RefTitle>Predictors of mortality and impact of aminoglycosides on outcome in listeriosis in a retrospective cohort study</RefTitle> <RefYear>2009</RefYear> <RefJournal>J Antimicrob Chemother</RefJournal> <RefPage>416-23</RefPage> <RefTotal>Mitj&#224; O, Pigrau C, Ruiz I, Vidal X, Almirante B, Planes AM, Molina I, Rodr&#237;guez D, Pahissa A. Predictors of mortality and impact of aminoglycosides on outcome in listeriosis in a retrospective cohort study. J Antimicrob Chemother. 2009 Aug;64(2):416-23. DOI: 10.1093&#47;jac&#47;dkp180</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1093&#47;jac&#47;dkp180</RefLink> </Reference> <Reference refNo="83"> <RefAuthor>Mu&#241;oz P</RefAuthor> <RefAuthor>Rojas L</RefAuthor> <RefAuthor>Bunsow E</RefAuthor> <RefAuthor>Saez E</RefAuthor> <RefAuthor>S&#225;nchez-Cambronero L</RefAuthor> <RefAuthor>Alcal&#225; L</RefAuthor> <RefAuthor>Rodr&#237;guez-Creixems M</RefAuthor> <RefAuthor>Bouza E</RefAuthor> <RefTitle>Listeriosis: An emerging public health problem especially among the elderly</RefTitle> <RefYear>2012</RefYear> <RefJournal>J Infect</RefJournal> <RefPage>19-33</RefPage> <RefTotal>Mu&#241;oz P, Rojas L, Bunsow E, Saez E, S&#225;nchez-Cambronero L, Alcal&#225; L, Rodr&#237;guez-Creixems M, Bouza E. Listeriosis: An emerging public health problem especially among the elderly. J Infect. 2012 Jan;64(1):19-33. DOI: 10.1016&#47;j.jinf.2011.10.006</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1016&#47;j.jinf.2011.10.006</RefLink> </Reference> <Reference refNo="84"> <RefAuthor>Lorber B</RefAuthor> <RefTitle>Comment on: Predictors of mortality and impact of aminoglycosides on outcome in listeriosis in a retrospective cohort study</RefTitle> <RefYear>2010</RefYear> <RefJournal>J Antimicrob Chemother</RefJournal> <RefPage>810</RefPage> <RefTotal>Lorber B. Comment on: Predictors of mortality and impact of aminoglycosides on outcome in listeriosis in a retrospective cohort study. J Antimicrob Chemother. 2010 Apr;65(4):810. DOI: 10.1093&#47;jac&#47;dkp497</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1093&#47;jac&#47;dkp497</RefLink> </Reference> <Reference refNo="85"> <RefAuthor>Clauss HE</RefAuthor> <RefAuthor>Lorber B</RefAuthor> <RefTitle>Central nervous system infection with Listeria monocytogenes</RefTitle> <RefYear>2008</RefYear> <RefJournal>Curr Infect Dis Rep</RefJournal> <RefPage>300-6</RefPage> <RefTotal>Clauss HE, Lorber B. Central nervous system infection with Listeria monocytogenes. Curr Infect Dis Rep. 2008 Jul;10(4):300-6. DOI: 10.1007&#47;s11908-008-0049-0</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1007&#47;s11908-008-0049-0</RefLink> </Reference> <Reference refNo="86"> <RefAuthor>Lorber B</RefAuthor> <RefTitle>Listeria monocytogenes</RefTitle> <RefYear>2005</RefYear> <RefBookTitle>Principles and practice of infectious diseases</RefBookTitle> <RefPage>2478-84</RefPage> <RefTotal>Lorber B. Listeria monocytogenes. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. 6th ed. Philadelphia: Elsevier Churchill Livingstone; 2005. p. 2478-84.</RefTotal> </Reference> <Reference refNo="87"> <RefAuthor>Deutsche Gesellschaft f&#252;r Neurologie</RefAuthor> <RefTitle></RefTitle> <RefYear>2012</RefYear> <RefBookTitle>Ambulant erworbene bakterielle (eitrige) Meningoenzephalitis. AWMF-Registernummer 030&#47;089</RefBookTitle> <RefPage></RefPage> <RefTotal>Deutsche Gesellschaft f&#252;r Neurologie. Ambulant erworbene bakterielle (eitrige) Meningoenzephalitis. AWMF-Registernummer 030&#47;089. 2012. (Leitlinien f&#252;r Diagnostik und Therapie in der Neurologie). Available from: http:&#47;&#47;www.awmf.org&#47;leitlinien&#47;detail&#47;ll&#47;030-089.html</RefTotal> <RefLink>http:&#47;&#47;www.awmf.org&#47;leitlinien&#47;detail&#47;ll&#47;030-089.html</RefLink> </Reference> <Reference refNo="88"> <RefAuthor>Viale P</RefAuthor> <RefAuthor>Furlanut M</RefAuthor> <RefAuthor>Cristini F</RefAuthor> <RefAuthor>Cadeo B</RefAuthor> <RefAuthor>Pavan F</RefAuthor> <RefAuthor>Pea F</RefAuthor> <RefTitle>Major role of levofloxacin in the treatment of a case of Listeria monocytogenes meningitis</RefTitle> <RefYear>2007</RefYear> <RefJournal>Diagn Microbiol Infect Dis</RefJournal> <RefPage>137-9</RefPage> <RefTotal>Viale P, Furlanut M, Cristini F, Cadeo B, Pavan F, Pea F. Major role of levofloxacin in the treatment of a case of Listeria monocytogenes meningitis. Diagn Microbiol Infect Dis. 2007 May;58(1):137-9. DOI: 10.1016&#47;j.diagmicrobio.2006.11.010</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1016&#47;j.diagmicrobio.2006.11.010</RefLink> </Reference> <Reference refNo="89"> <RefAuthor>Cabellos C</RefAuthor> <RefAuthor>Martinez-Lacasa J</RefAuthor> <RefAuthor>Martos A</RefAuthor> <RefAuthor>Tubau F</RefAuthor> <RefAuthor>Fern&#225;ndez A</RefAuthor> <RefAuthor>Viladrich PF</RefAuthor> <RefAuthor>Gudiol F</RefAuthor> <RefTitle>Influence of dexamethasone on efficacy of ceftriaxone and vancomycin therapy in experimental pneumococcal meningitis</RefTitle> <RefYear>1995</RefYear> <RefJournal>Antimicrob Agents Chemother</RefJournal> <RefPage>2158-60</RefPage> <RefTotal>Cabellos C, Martinez-Lacasa J, Martos A, Tubau F, Fern&#225;ndez A, Viladrich PF, Gudiol F. Influence of dexamethasone on efficacy of ceftriaxone and vancomycin therapy in experimental pneumococcal meningitis. Antimicrob Agents Chemother. 1995 Sep;39(9):2158-60. DOI: 10.1128&#47;AAC.39.9.2158</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1128&#47;AAC.39.9.2158</RefLink> </Reference> <Reference refNo="90"> <RefAuthor>Branen JK</RefAuthor> <RefAuthor>Davidson PM</RefAuthor> <RefTitle>Enhancement of nisin, lysozyme, and monolaurin antimicrobial activities by ethylenediaminetetraacetic acid and lactoferrin</RefTitle> <RefYear>2004</RefYear> <RefJournal>Int J Food Microbiol</RefJournal> <RefPage>63-74</RefPage> <RefTotal>Branen JK, Davidson PM. Enhancement of nisin, lysozyme, and monolaurin antimicrobial activities by ethylenediaminetetraacetic acid and lactoferrin. Int J Food Microbiol. 2004 Jan;90(1):63-74. DOI: 10.1016&#47;S0168-1605(03)00172-7</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1016&#47;S0168-1605(03)00172-7</RefLink> </Reference> <Reference refNo="91"> <RefAuthor>Longhi C</RefAuthor> <RefAuthor>Conte MP</RefAuthor> <RefAuthor>Penta M</RefAuthor> <RefAuthor>Cossu A</RefAuthor> <RefAuthor>Antonini G</RefAuthor> <RefAuthor>Superti F</RefAuthor> <RefAuthor>Seganti L</RefAuthor> <RefTitle>Lactoferricin influences early events of Listeria monocytogenes infection in THP-1 human macrophages</RefTitle> <RefYear>2004</RefYear> <RefJournal>J Med Microbiol</RefJournal> <RefPage>87-91</RefPage> <RefTotal>Longhi C, Conte MP, Penta M, Cossu A, Antonini G, Superti F, Seganti L. Lactoferricin influences early events of Listeria monocytogenes infection in THP-1 human macrophages. J Med Microbiol. 2004 Feb;53(Pt 2):87-91. DOI: 10.1099&#47;jmm.0.05367-0</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1099&#47;jmm.0.05367-0</RefLink> </Reference> <Reference refNo="92"> <RefAuthor>Palumbo D</RefAuthor> <RefAuthor>Iannaccone M</RefAuthor> <RefAuthor>Porta A</RefAuthor> <RefAuthor>Capparelli R</RefAuthor> <RefTitle>Experimental antibacterial therapy with puroindolines, lactoferrin and lysozyme in Listeria monocytogenes-infected mice</RefTitle> <RefYear>2010</RefYear> <RefJournal>Microbes Infect</RefJournal> <RefPage>538-45</RefPage> <RefTotal>Palumbo D, Iannaccone M, Porta A, Capparelli R. Experimental antibacterial therapy with puroindolines, lactoferrin and lysozyme in Listeria monocytogenes-infected mice. Microbes Infect. 2010 Jul;12(7):538-45. DOI: 10.1016&#47;j.micinf.2010.03.010</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1016&#47;j.micinf.2010.03.010</RefLink> </Reference> <Reference refNo="93"> <RefAuthor>Berchtold C</RefAuthor> <RefAuthor>Panthel K</RefAuthor> <RefAuthor>Jellbauer S</RefAuthor> <RefAuthor>K&#246;hn B</RefAuthor> <RefAuthor>Roider E</RefAuthor> <RefAuthor>Partilla M</RefAuthor> <RefAuthor>Heesemann J</RefAuthor> <RefAuthor>Endres S</RefAuthor> <RefAuthor>Bourquin C</RefAuthor> <RefAuthor>R&#252;ssmann H</RefAuthor> <RefTitle>Superior protective immunity against murine listeriosis by combined vaccination with CpG DNA and recombinant Salmonella enterica serovar typhimurium</RefTitle> <RefYear>2009</RefYear> <RefJournal>Infect Immun</RefJournal> <RefPage>5501-8</RefPage> <RefTotal>Berchtold C, Panthel K, Jellbauer S, K&#246;hn B, Roider E, Partilla M, Heesemann J, Endres S, Bourquin C, R&#252;ssmann H. Superior protective immunity against murine listeriosis by combined vaccination with CpG DNA and recombinant Salmonella enterica serovar typhimurium. Infect Immun. 2009 Dec;77(12):5501-8. DOI: 10.1128&#47;IAI.00700-09</RefTotal> <RefLink>http:&#47;&#47;dx.doi.org&#47;10.1128&#47;IAI.00700-09</RefLink> </Reference> </References> <Media> <Tables> <Table format="png"> <MediaNo>1</MediaNo> <MediaID>1</MediaID> <Caption><Pgraph><Mark1>Table 1: Activities of some antibiotics on Listeria monycotogenes in vitro, in cell cultures and in animal experiments &#91;7&#93;</Mark1></Pgraph></Caption> </Table> <NoOfTables>1</NoOfTables> </Tables> <Figures> <NoOfPictures>0</NoOfPictures> </Figures> <InlineFigures> <NoOfPictures>0</NoOfPictures> </InlineFigures> <Attachments> <NoOfAttachments>0</NoOfAttachments> </Attachments> </Media> </OrigData> </GmsArticle>