[show abstract][hide abstract] ABSTRACT: An important question regarding the biologic implications of antibiotic-resistant microbes is how resistance impacts the organism's overall fitness and virulence. Currently it is generally thought that antibiotic resistance carries a fitness cost and reduces virulence. For the human pathogen Pseudomonas aeruginosa, treatment with carbapenem antibiotics is a mainstay of therapy that can lead to the emergence of resistance, often through the loss of the carbapenem entry channel OprD. Transposon insertion-site sequencing was used to analyze the fitness of 300,000 mutants of P. aeruginosa strain PA14 in a mouse model for gut colonization and systemic dissemination after induction of neutropenia. Transposon insertions in the oprD gene led not only to carbapenem resistance but also to a dramatic increase in mucosal colonization and dissemination to the spleen. These findings were confirmed in vivo with different oprD mutants of PA14 as well as with related pairs of carbapenem-susceptible and -resistant clinical isolates. Compared with OprD(+) strains, those lacking OprD were more resistant to killing by acidic pH or normal human serum and had increased cytotoxicity against murine macrophages. RNA-sequencing analysis revealed that an oprD mutant showed dramatic changes in the transcription of genes that may contribute to the various phenotypic changes observed. The association between carbapenem resistance and enhanced survival of P. aeruginosa in infected murine hosts suggests that either drug resistance or host colonization can cause the emergence of more pathogenic, drug-resistant P. aeruginosa clones in a single genetic event.
Proceedings of the National Academy of Sciences 11/2013; · 9.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: As opposed to Enterococcus faecalis that is intrinsically resistant to lincosamides, streptogramins A, and pleuromutilins (LSAP phenotype) by production of the ABC protein Lsa(A), Enterococcus faecium is naturally susceptible. Since this phenotype may be selected in vivo by quinupristin-dalfopristin (Q-D), the aim of the study was to investigate the molecular mechanism of the acquired LSAP resistance in E. faecium. Six LSAP-resistant in vitro mutants of E. faecium HM1070 were studied as well as three different pairs of clinical isolates (pre- and post-exposure to Q-D). Full genome sequence of an in vitro mutant (E. faecium UCN90B) was determined using the 454 sequencing technology, and was compared with that of the parental strain. Single-nucleotide replacement was carried out to confirm the role of this mutation. By comparative genomic analysis, a point mutation was found within a 1503-bp gene coding for an ABC homologue showing 66% amino-acid identity with Lsa(A). This mutation (C1349T) led to an amino-acid substitution (Thr450Ile). The identical mutation was identified in all in vitro and in vivo resistant strains, but was not present in susceptible strains. The wild-type allele was named eat(A) (for Enterococcus ABC transporter) and its mutated allelic variant, eat(A)v. The introduction of eat(A)v from UCN90B into HM1070 conferred the LSAP phenotype whereas that of eat(A) from HM1070 into UCN90B restored entire susceptibility. This is the first description of the molecular mechanism of acquired LSAP resistance in E. faecium. Characterization of the biochemical mechanism of resistance and the physiological role of this ABC protein need further investigations.
Antimicrobial Agents and Chemotherapy 07/2013; · 4.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: Rhodococcus equi, the causal agent of rhodococcosis, is a major pathogen of foals and is also responsible of severe infections in immunocompromised humans. Of great concern, resistant strains to currently used antibiotics have emerged. As the number of drugs that are efficient in vivo is limited because of the intracellular localization of the bacterium inside macrophages, new active but cell-permeant drugs will be needed in the near future. In the present study, we evaluated, by in vitro and ex vivo experiments, the ability of the alpha helical equine antimicrobial peptide eCATH1 to kill intracellular bacterial cells. Moreover, the therapeutic potential of the peptide was assessed in an experimental rhodococcosis induced in mice while the in vivo toxicity was evaluated by behavioral and histopathological analysis. The study revealed that eCATH1 significantly reduced the number of bacteria inside macrophages. Furthermore, the bactericidal potential of the peptide was maintained in vivo at doses that appeared to have no visible deleterious effects for the mice even after 7 days of treatment. Indeed, daily subcutaneous injections of 1 mg/kg body weight of eCATH1 led to a significant reduction of the bacterial load in organs comparable to that obtained after treatment with 10 mg/kg body weight of rifampin. Interestingly, the combination of the peptide with rifampin showed a synergistic interaction in both ex vivo and in vivo experiments. These results emphasize the therapeutic potential that eCATH1 represents in the treatment of rhodococcosis.
Antimicrobial Agents and Chemotherapy 07/2013; · 4.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: Unique resistance to lincosamides (L phenotype) due to the production of nucleotidyltransferases (Lnu) is uncommon among Gram-positive bacteria. The aim of the study was to characterize the L phenotype in a clinical isolate of the Streptococcus milleri group.
The strain UCN93 was recovered from neonatal specimens and from the mother's vaginal swab. Identification was confirmed by sequencing of the sodA gene. Antimicrobial susceptibility testing was carried out by the disc diffusion method, while MICs were determined using the agar dilution method. Screening for lnu(A), lnu(B), lnu(C) and lnu(D) genes was performed by PCR. Genetic environment and support were determined by thermal asymmetric interlaced PCR and PCR mapping. The transfer of lincomycin resistance was also attempted by conjugation.
UCN93 was unambiguously identified as Streptococcus anginosus. It was susceptible to all tested antibiotics, except lincomycin (MIC, 8 mg/L) and tetracycline (2 mg/L). The lnu(C) gene was found to be responsible for the L phenotype. It was shown that lnu(C) was associated with a gene coding for a transposase within a structure similar to the transposon MTnSag1, described once in Streptococcus agalactiae. Since MTnSag1 was found to be mobilized by Tn916 and S. anginosus UCN93 harboured a Tn916 transposon, several attempts at transfer were performed but they all failed. The lnu(C)-containing genetic element was inserted into a chromosomal intergenic sequence of S. anginosus.
Since lnu(C) has been detected in only one S. agalactiae clinical isolate so far, this is its second description among clinically relevant streptococci.
Journal of Antimicrobial Chemotherapy 06/2013; · 5.34 Impact Factor
[show abstract][hide abstract] ABSTRACT: To determine if hospital effluent input has an ecological impact on downstream aquatic environment, antibiotic resistance in Enterococcus spp. along a medical center-retirement home-wastewater treatment plant-river continuum in France was determined using a culture-based method. Data on antibiotic consumption among hospitalized and general populations and levels of water contamination by antibiotics were collected. All isolated enterococci were genotypically identified to the species level, tested for in vitro antibiotic susceptibility, and typed by multilocus sequence typing. The erm(B) and mef(A) (macrolide resistance) and tet(M) (tetracycline resistance) genes were detected by PCR. All along the continuum, from 89 to 98% of enterococci, according to the sampled site, were identified as Enterococcus faecium. All E. faecium isolates from hospital and retirement home effluents were multiply resistant to antibiotics, contained erm(B) and mef(A) genes, and belonged to the hospital-adapted clonal complex 17 (CC17). Even though this species remained dominant in the downstream continuum, the relative proportion of CC17 isolates progressively decreased in favor of other subpopulations of E. faecium, more diverse, less resistant to antibiotics, devoid of the classical macrolide-resistance genes, and belonging to various sequence types. Antibiotic concentrations in waters were far below the MICs for susceptible isolates. CC17 E. faecium were probably acquired in the gastro-intestinal tract of patients under the selective pressure of administered antibiotics and then excreted together with the resistance genes in waters to progressively decrease along the continuum.
Applied and environmental microbiology 02/2013; · 3.69 Impact Factor
[show abstract][hide abstract] ABSTRACT: Twenty-five years ago, isolation of vancomycin-resistant Enterococcus faecium (VREm) was reported both in the UK and in France. Since then, VREm has spread worldwide in hospitals. Hospital outbreaks appeared to be related to the evolution since the end of 1980s of a subpopulation of E. faecium highly resistant to ampicillin and fluoroquinolones (the so-called clonal complex CC17) that later acquired resistance to vancomycin. CC17 isolates are presumably better adapted than other E. faecium isolates to the constraints of the hospital environment and most contain mobile genetic elements, phage genes, genes encoding membrane proteins, regulatory genes, a putative pathogenicity island and megaplasmids. Colonization and persistence are major features of VREm. Inherent characteristics of E. faecium including a remarkable genome plasticity, in part due to acquisition of IS elements, in particular IS16, have facilitated niche adaptation of this distinct E. faecium subpopulation that is multiply resistant to antibiotics. Quinupristin/dalfopristin and linezolid are licensed for the treatment of VREm infections, with linezolid often used as a first-line treatment. However, the emergence of plasmid-mediated resistance to linezolid by production of a Cfr methyltransferase in Enterococcus faecalis is worrying. Daptomycin has not been extensively evaluated for the treatment of VREm infections and resistant mutants have been selected under daptomycin therapy. Although control of VRE is challenging, a laissez-faire policy would result in an increased number of infections and would create an irreversible situation. Although so far unsuccessful, dissemination of glycopeptide-resistant Staphylococcus aureus with van genes acquired from resistant enterococci cannot be ruled out.
Journal of Antimicrobial Chemotherapy 12/2012; · 5.34 Impact Factor
[show abstract][hide abstract] ABSTRACT: The purpose of this retrospective study was to evaluate the pathogenic role of Corynebacterium species in lower respiratory tract infections as well as their routine laboratory investigation. From April 2007 to August 2009, 27 clinical isolates were significantly recovered from respiratory specimens of 27 different patients clinically suspected of having lower respiratory tract infections. The average age of patients was 65 years, while 22 (81%) patients presented at least 1 predisposing condition. Of the 27 patients, 15 (56%) were classified as infected according to Centers for Disease Control and Prevention/National Healthcare Safety Network criteria, with 93% of infections being hospital acquired. All isolates were accurately identified to the species level using molecular methods (i.e., 17 Corynebacterium pseudodiphtheriticum, 7 Corynebacterium striatum, and 3 Corynebacterium accolens), whereas phenotypic methods remained frequently unreliable for identifying C. striatum and C. accolens strains. All tested isolates were susceptible to amoxicillin, imipenem, vancomycin, linezolid, and tigecycline, whereas most of them were resistant to erythromycin.
[show abstract][hide abstract] ABSTRACT: Oxidative stress serves as an important host/environmental signal that triggers a wide range of responses in microorganisms. Here, we identified an oxidative stress sensor and response regulator in the important multidrug-resistant nosocomial pathogen Enterococcus faecium belonging to the MarR family and called AsrR (antibiotic and stress response regulator). The AsrR regulator used cysteine oxidation to sense the hydrogen peroxide which results in its dissociation to promoter DNA. Transcriptome analysis showed that the AsrR regulon was composed of 181 genes, including representing functionally diverse groups involved in pathogenesis, antibiotic and antimicrobial peptide resistance, oxidative stress, and adaptive responses. Consistent with the upregulated expression of the pbp5 gene, encoding a low-affinity penicillin-binding protein, the asrR null mutant was found to be more resistant to β-lactam antibiotics. Deletion of asrR markedly decreased the bactericidal activity of ampicillin and vancomycin, which are both commonly used to treat infections due to enterococci, and also led to over-expression of two major adhesins, acm and ecbA, which resulted in enhanced in vitro adhesion to human intestinal cells. Additional pathogenic traits were also reinforced in the asrR null mutant including greater capacity than the parental strain to form biofilm in vitro and greater persistance in Galleria mellonella colonization and mouse systemic infection models. Despite overexpression of oxidative stress-response genes, deletion of asrR was associated with a decreased oxidative stress resistance in vitro, which correlated with a reduced resistance to phagocytic killing by murine macrophages. Interestingly, both strains showed similar amounts of intracellular reactive oxygen species. Finally, we observed a mutator phenotype and enhanced DNA transfer frequencies in the asrR deleted strain. These data indicate that AsrR plays a major role in antimicrobial resistance and adaptation for survival within the host, thereby contributes importantly to the opportunistic traits of E. faecium.
[show abstract][hide abstract] ABSTRACT: Twenty-three strains of Staphylococcus aureus with borderline resistance to oxacillin were studied. These strains were not detected by the cefoxitin test, tests for penicillin-binding protein 2a (PBP2a), mecA, and mecA(LGA251) were negative, and the strains were genetically unrelated. To detect all strains resistant to oxacillin, laboratories should routinely test for both cefoxitin and oxacillin.
Journal of clinical microbiology 07/2012; 50(10):3345-8. · 4.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: AIM: We report the emergence of Staphylococcus aureus resistant to pristinamycin in Tunisia, and the characterization of the mechanisms of resistance to macrolides and streptogramins. METHODS AND RESULTS: Five strains of S. aureus resistant to pristinamycin were recovered from the department of dermatology in a Tunisian university hospital from skin samples after oral use of pristinamycin between 2004 and 2007. Susceptibility testing showed that all isolates were resistant to quinupristin-dalfopristin (MIC=4-32mg/L), lincomycin, gentamicin, kanamycin, tobramycin, tetracycline and rifampin. One isolate was susceptible to erythromycin. All five strains were closely related after analysis by pulsed-field gel electrophoresis. erm(C) was amplified from three strains and erm(A) from one strain. vga and vat genes were amplified from all strains. None of the isolates carried the vgb gene. The vga and vat genes were typed as vga(B) and vat(B) by restriction profiles analysis after electrophoresis. CONCLUSION: This is the first report of clonal emergence of S. aureus resistant to pristinamycin carrying vga and vat genes in Tunisia. The role of selective pressure of pristinamycin use is certainly the main explanation of this emergence. So we must reduce the utilisation of this antibiotic for the treatment of cutaneous and bone infectious disease caused by multidrug resistant bacteria.
[show abstract][hide abstract] ABSTRACT: Rhodococcus equi, the causal agent of rhodococcosis, is a severe pathogen of foals but also of immunodeficient humans, causing bronchopneumonia. The pathogen is often found together with Klebsiella pneumoniae or Streptococcus zooepidemicus in foals. Of great concern is the fact that some R. equi strains are already resistant to commonly used antibiotics. In the present study, we evaluated the in vitro potential of two equine antimicrobial peptides (AMPs), eCATH1 and DEFA1, as new drugs against R. equi and its associated pathogens. The peptides led to growth inhibition and death of R. equi and S. zooepidemicus at low micromolar concentrations. Moreover, eCATH1 was able to inhibit growth of K. pneumoniae. Both peptides caused rapid disruption of the R. equi membrane, leading to cell lysis. Interestingly, eCATH1 had a synergic effect together with rifampin. Furthermore, eCATH1 was not cytotoxic against mammalian cells at bacteriolytic concentrations and maintained its high killing activity even at physiological salt concentrations. Our data suggest that equine AMPs, especially eCATH1, may be promising candidates for alternative drugs to control R. equi in mono- and coinfections.
Antimicrobial Agents and Chemotherapy 01/2012; 56(4):1749-55. · 4.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: Glycopeptides, vancomycin and teicoplanin, are used parenterally mostly in infections due to staphylococci and enterococci resistant to β-lactams or in case of intolerance to these antibiotics. Both glycopeptides should be tested since susceptibility testing results may be dissociated. Both staphylococci and enterococci have developed resistance to glycopeptides, the first ones by mutation and the latter (mostly the Enterococcus faecium species) by gene acquisition. The disc-diffusion method poorly suits to the test of glycopeptides against staphylococci but is better suited for enterococci only if agar plates are incubated for 24 h. Various criteria in the lecture of zone diameters inhibition are to be considered that may lead to suspect resistance. In this case, MICs should be determined to categorize the isolates. Some Staphylococcus aureus isolates susceptible to vancomycin may present resistant sub-populations (hetero-VISA). For enterococci, the acquired resistance to vancomycin (VanA ou VanB) in E. faecium and Enterococcus faecalis should be distinguished from the intrinsic resistance (VanC) or Enterococcus gallinarum and Enterococcus casseliflavus since only the first one is associated with outbreaks and should be notified to health authorities.
Revue Francophone des Laboratoires 01/2012; 2012(445):41–46.
[show abstract][hide abstract] ABSTRACT: Clin Microbiol Infect ABSTRACT: EUCAST expert rules have been developed to assist clinical microbiologists and describe actions to be taken in response to specific antimicrobial susceptibility test results. They include recommendations on reporting, such as inferring susceptibility to other agents from results with one, suppression of results that may be inappropriate, and editing of results from susceptible to intermediate or resistant or from intermediate to resistant on the basis of an inferred resistance mechanism. They are based on current clinical and/or microbiological evidence. EUCAST expert rules also include intrinsic resistance phenotypes and exceptional resistance phenotypes, which have not yet been reported or are very rare. The applicability of EUCAST expert rules depends on the MIC breakpoints used to define the rules. Setting appropriate clinical breakpoints, based on treating patients and not on the detection of resistance mechanisms, may lead to modification of some expert rules in the future.
Clinical Microbiology and Infection 10/2011; · 4.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: Sensitive markers of infection are rare or of limited validity in neutropenic patients. Procalcitonin (PCT), a precursor protein of calcitonin, is a specific and sensitive marker of severe bacterial infections during short-term neutropenia. Because the value of PCT measurements among patients undergoing long periods of neutropenia remains uncertain and because several mechanisms, such as bacterial or fungal infections, reactions to drugs or blood products or tumor-associated events, can cause fever, we described the dynamics of PCT in 29 acute myeloid leukemia (AML) patients with 39 instances of chemotherapy-induced neutropenia. Plasma levels of PCT were determined prospectively by an immunoluminometric assay every four days starting at the onset of chemotherapy and continuing until the resolution of fever. We found that bacteremia did increase PCT levels above 0.5ng/mL and these levels predicted bacteremia at day 15 of chemotherapy. This finding may be relevant in the decision to alter antibiotic regimens to decrease toxicity and cost when patients remain febrile at day 15.
Leukemia research 08/2011; 35(10):1294-6. · 2.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: Enterococcus faecium UCN71, isolated from a blood culture, was resistant to low levels of vancomycin (MIC, 16 μg/ml) but susceptible to teicoplanin (MIC, 0.5 μg/ml). No amplification was observed with primers specific for the previously described glycopeptide resistance ligase genes, but a PCR product corresponding to a gene called vanN was obtained using degenerate primers and was sequenced. The deduced VanN protein was related (65% identity) to the d-alanine:d-serine VanL ligase. The organization of the vanN gene cluster, determined using degenerate primers and by thermal asymmetric interlaced (TAIL)-PCR, was similar to that of the vanC operons. A single promoter upstream from the resistance operon was identified by rapid amplification of cDNA ends (RACE)-PCR. The presence of peptidoglycan precursors ending in d-serine and d,d-peptidase activities in the absence of vancomycin indicated constitutive expression of the resistance operon. VanN-type resistance was transferable by conjugation to E. faecium. This is the first report of transferable d-Ala-d-Ser-type resistance in E. faecium.
Antimicrobial Agents and Chemotherapy 08/2011; 55(10):4606-12. · 4.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: In our tertiary university hospital, fluoroquinolones were prohibited during 2001 leading to a 90% reduction in their use. Our objective was to examine the trends in meticillin-resistant Staphylococcus aureus (MRSA) following the reintroduction of fluoroquinolones. We conducted a 10-year time-series analysis of monthly MRSA according to: (i) period of fluoroquinolone restriction (January 2001 to January 2002); (ii) period of fluoroquinolone increase up to pre-restriction levels (January 2002 to December 2004); and (iii) an observational period including the implementation of a hand hygiene campaign with alcohol-based hand rub (January 2005 to June 2009). We used segmented linear autoregression analysis to assess trends between adjacent periods. Fluoroquinolone use increased from 5.2 defined daily doses (DDD) per 1000 patient-days in 2001 to 56.6 DDD per 1000 patient-days in 2005 reaching pre-restriction fluoroquinolone levels (P<0.001) and remained stable during 2005-2010 (P=0.65). The monthly proportion of MRSA decreased during the period of FQ restriction (-0.49 per month, P<0.05). The reintroduction of fluoroquinolones was associated with a significant increase in MRSA (+0.68 per month, P<0.02) compared to the previous period. During period 3, we observed a significant change in MRSA (-5.9, P<0.002) compared to the previous period (-0.32 per month, P<0.001). During the latter period, hand hygiene was promoted and alcohol-based hand-rub consumption increased from 3411 L in 2005 to 14,599 L in 2009. This study reinforces the rationale for a hospital-wide fluoroquinolone formulary policy to control MRSA and suggests that it has an additive effect with a hand hygiene promotion.
The Journal of hospital infection 06/2011; 78(2):118-22. · 3.01 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to determine the in vitro activity of six new antimicrobial agents against glycopeptide-resistant enterococci (GRE) strains from France.
Sixty epidemiologically unrelated clinical isolates of Enterococcus faecium (vanA or vanB), received at the National Reference Centre for Enterococci (CNR-Enc) between 2006 and 2008, were studied. The MICs of the following antibiotics were determined by broth microdilution according to Antibiogram Committee of the French Society for Microbiology (CA-SFM) guidelines: quinupristin-dalfopristin (Q-D), linezolid (LZD), daptomycin (DPT), tigecycline (TGC), ceftobiprole (CFT), and telavancin (TLV). Strains were classified using clinical breakpoints recommended by the CA-SFM (Q-D, LZD, TGC), or the Clinical and Laboratory Standards Institute (DPT).
All strains were susceptible to LZD and DPT (MIC(90), 4 and 2μg/ml, respectively) and only a single strain presented intermediate susceptibility to tigecycline (MIC(90), 0.25μg/ml). Thirty percent of strains were resistant to Q-D (MIC(90), 4μg/ml), and CFT was constantly inactive (MIC(90), 64μg/ml). Finally, TLV showed low-level MICs (MIC(90), 0.5μg/ml) against vanB-positive isolates but not against vanA-positive isolates (MIC(90), 8μg/ml).
Although several antibiotics are still active against GRE, it is essential to maintain an active antimicrobial resistance surveillance for these microorganisms considered as a model of multidrug resistance with a potential to transfer resistance to other bacterial species (e.g. Staphylococcus aureus).
[show abstract][hide abstract] ABSTRACT: The detection of Mycobacterium tuberculosis using a new commercial real-time polymerase chain reaction (PCR) assay (Xpert™ MTB/RIF) was evaluated on 91 respiratory and 89 non-respiratory samples recovered from 132 patients suspected of tuberculosis (TB). Overall, 31 (17.2%) of the 180 samples, including 17 respiratory and 14 non-respiratory (respectively 17 and 12 PCR-positive), yielded M. tuberculosis on culture. The sensitivity and specificity of PCR were respectively 100% and 100%, and 85.7% and 97.3% for respiratory and non-respiratory samples. Although the test is validated only for respiratory samples, our findings suggest that it could be useful for the diagnosis of extra-pulmonary TB.
The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 04/2011; 15(4):553-5. · 2.61 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aims of this study were to determine the in vitro activity profile of ceftobiprole, a pyrrolidinone cephalosporin, against a large number of bacterial pathogens and to propose zone diameter breakpoints for clinical categorisation according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) minimum inhibitory concentration (MIC) breakpoints. MICs of ceftobiprole were determined by broth microdilution against 1548 clinical isolates collected in eight French hospitals. Disk diffusion testing was performed using 30 μg disks according to the method of the Comité de l'Antibiogramme de la Société Française de Microbiologie (CA-SFM). The in vitro activity of ceftobiprole, expressed by MIC(50/90) (MICs for 50% and 90% of the organisms, respectively) (mg/L), was as follows: meticillin-susceptible Staphylococcus aureus, 0.25/0.5; meticillin-resistant S. aureus (MRSA), 1/2; meticillin-susceptible coagulase-negative staphylococci (CoNS), 0.12/0.5; meticillin-resistant CoNS, 1/2; penicillin-susceptible Streptococcus pneumoniae, ≤ 0.008/0.03; penicillin-resistant S. pneumoniae, 0.12/0.5; viridans group streptococci, 0.03/0.12; β-haemolytic streptococci, ≤ 0.008/0.016; Enterococcus faecalis, 0.25/1; Enterococcus faecium, 64/128; Enterobacteriaceae, 0.06/32; Pseudomonas aeruginosa, 4/16; Acinetobacter baumannii, 0.5/64; Haemophilus influenzae, 0.03/0.12; and Moraxella catarrhalis, 0.25/0.5. According to the regression curve, zone diameter breakpoints could be 28, 26, 24 and 22 mm for MICs of 0.5, 1, 2 and 4 mg/L respectively. In conclusion, this study confirms the potent in vitro activity of ceftobiprole against many Gram-positive bacteria, including MRSA but not E. faecium, whilst maintaining a Gram-negative spectrum similar to the advanced-generation cephalosporins such as cefepime. Thus ceftobiprole appears to be well suited for the empirical treatment of a variety of healthcare-associated infections.
International journal of antimicrobial agents 03/2011; 37(3):235-9. · 3.03 Impact Factor