In our experience, linezolid has been a valid alternative drug in the management of multidrug-resistant tuberculosis. The prolonged use of linezolid is frequently associated with toxicity, mainly anaemia and peripheral neuropathy, that requires special management.

Background. We report the emergence and spread of metallo-b-lactamases (MBLs) among enterobacterial isolates at Ramó n y Cajal University Hospital (Madrid, Spain).Methods and results. During the period from March 2005 through September 2006, 25 patients (52% of whom were in the intensive care unit) were infected and/or colonized with single or different MBL-producing Enterobacteriaceae isolates (Klebsiella pneumoniae, 14 patients; Enterobacter cloacae, 12 patients; Escherichia coli, 1 patient; and/or Klebsiella oxytoca, 1 patient). Clonal analysis (XbaI pulsed-field gel electrophoresis) revealed that all K. pneumoniae isolates belonged to the same clone, but 6 patterns were found among the E. cloacae isolates. Carbapenems were affected to different degrees (minimum inhibitory concentration, р1 to 18 mg/mL), as were aminoglycosides and ciprofloxacin. The bla VIM-1 MBL gene was present in all isolates; in addition, the bla SHV-12 extended-spectrum b-lactamase gene was detected in K. pneumoniae and E. coli isolates. The bla VIM-1 gene was detected within a 4.0-kb class 1 integron (bla VIM-1 -aacA4-dfrII-aadA1-catB2) in K. pneumoniae and E. coli and in a 2.5-kb class 1 integron (bla VIM-1 -aacA4-aadA1) in E. cloacae and K. oxytoca isolates. The bla VIM-1 gene was transferable (filter-mating) in 14 of 14 K. pneumoniae isolates, 4 of 11 E. cloacae isolates, and 1 of 1 E. coli isolate. A 60-kb plasmid belonging to the IncI1 group was detected in the epidemic VIM-1-K. pneumoniae clone. Plasmids of 300-or 435-kb belonging to IncH12 group were found among E. cloacae isolates.Conclusions. K. pneumoniae-MBL monoclonal epidemics coexisted with E. cloacae-MBL multiclonal epidemics in our hospital. The spread of the bla VIM-1 gene among Enterobacteriaceae was driven by clonal spread associated with intergeneric plasmid transfer with different class I integron platforms. Such complex epidemiology might anticipate endemicity and should be considered for the design of containment epidemiology strategies.

ALT appears as an effective conservative treatment in the management of CRB associated with long-term intravascular devices (84% in the present series), especially in infections caused by coagulase-negative staphylococci.

Rapid identification of patients who are colonized with carbapenemase-producing organisms (CPO) is included in multiple national guidelines for containment of these organisms. In a multisite study, we evaluated the performance of the Cepheid Xpert Carba-R assay, a qualitative diagnostic test that was designed for the rapid detection and differentiation of the blaKPC, blaNDM, blaVIM, blaOXA-48, and blaIMP-1 genes from rectal swab specimens. A double rectal swab set was collected from 383 patients admitted at four institutions (2 in the United States, 1 in the United Kingdom, 1 in Spain). One swab was used for reference culture (MacConkey broth containing 1 mg/liter of meropenem and subcultured to a MacConkey agar plate with a 10-μg meropenem disk) and for sequencing of DNA obtained from carbapenem-nonsusceptible isolates for carbapenemase identification. The other swab was used for the Xpert Carba-R assay. In addition to the clinical rectal swabs, 250 contrived specimens (108 well-characterized CPO and 142 negative controls spiked onto negative rectal swabs) were tested. Overall, 149/633 (23.5%) samples were positive by the Xpert Carba-R assay. In 6 samples, multiple targets were detected (4 VIM/OXA-48, 1 IMP-1/NDM, and 1 NDM/KPC). The Xpert Carba-R assay detected 155 targets (26 IMP-1, 30 VIM, 27 NDM, 33 KPC, 39 OXA-48) within a time range of 32 to 48 min. The sensitivity, specificity, and positive and negative predictive values of the Xpert Carba-R assay compared to those of the reference culture and sequencing results were 96.6% (95% confidence interval [CI], 92.2% to 98.9%), 98.6% (95% CI, 97.1% to 99.4%), 95.3%, and 99.0%, respectively. The Cepheid Xpert Carba-R assay is an accurate and rapid test to identify rectal colonization with CPO, which can guide infection control programs to limit the spread of these organisms.

The emergence of bla VIM-1 within four different genetic platforms from distinct Enterobacteriaceae and Pseudomonas aeruginosa isolates in an area with a low prevalence of metallo-␤-lactamase producers is reported. Forty-three VIM-1-producing isolates (including 19 Enterobacter cloacae, 2 Escherichia coli, and 2 P. aeruginosa isolates, 18 Klebsiella pneumoniae isolate, and 2 Klebsiella oxytoca isolate) recovered from 2005 to 2007 and corresponding to 15 pulsed-field gel electrophoresis types were studied. The Enterobacteriaceae isolates corresponded to a hospital outbreak, and the P. aeruginosa isolates were sporadically recovered. The genetic context of the integrons carrying bla VIM-1 (arbitrarily designated types A, B, C, and D) was characterized by PCR mapping based on known Tn402 and mercury transposons and further sequencing. Among Enterobacteriaceae isolates, bla VIM-1 was part of integrons located either in an In2-Tn402 element linked to Tn21 (type A; In110-bla VIM-1 -aacA4-aadA1) or in a Tn402 transposon lacking the whole tni module [type B; In113-bla VIM-1 -aacA4-dhfrII (also called dfrB1)-aadA1-catB2] and the transposon was associated with an IncHI2 or IncI1 plasmid, respectively. Among P. aeruginosa isolates, bla VIM-1 was part of a new gene cassette array located in a defective Tn402 transposon carrying either tniB⌬3 and tniA (type C; bla VIM-1 -aadA1) or tniC and ⌬tniQ (type D; bla VIM-1 -aadB), and both Tn402 variants were associated with conjugative plasmids of 30 kb. The dissemination of bla VIM-1 was associated with different genetic structures and bacterial hosts, depicting a complex emergence and evolutionary network scenario in our facility, Ramón y Cajal University Hospital, Madrid, Spain. Knowledge of the complex epidemiology of bla VIM-1 is necessary to control this emerging threat.

During the 2 year period following the emergence of non-ST258 KPC-3-producing K. pneumoniae isolates in our institution, the blaKPC-3 and blaKPC-2 genes efficiently penetrated other Enterobacteriaceae lineages. Non-ST258 K. pneumoniae isolates were mostly responsible for the dissemination of KPC enzymes, producing a complex epidemiological picture.

Susceptibility results with low reproducibility by the same or different methods have been observed for metallo-beta-lactamase (MBL)-producing Enterobacteriaceae. Eighteen VIM-1-producing Klebsiella pneumoniae isolates (one per patient) belonging to a single epidemic clone in our hospital (2005 to 2008) but with different susceptibilities to carbapenems were studied. Imipenem MICs ranged from 8 to >128 mg/liter by standard CLSI microdilution, from <1 to >8 mg/liter by the semiautomatic Wider system, and from 0.75 to >32 mg/liter by Etest. Meropenem MICs ranged from 0.5 to 128, <1 to >8, and 0.38 to >32 mg/liter, respectively. Ertapenem MICs by CLSI microdilution and Etest ranged from 1 to 64 and 0.75 to >32 mg/liter, respectively. The rates of essential agreement (؎1 log 2 dilution) for imipenem and meropenem MICs between the Wider system and the reference microdilution method were 45% and 49%, respectively. Those between Etest and the reference microdilution method for imipenem, meropenem, and ertapenem MICs were 33%, 67%, and 84%. The rates of very major errors for the Wider system and Etest were 33% and 28% for imipenem and 25% and 75% for meropenem, respectively. Low MIC reproducibility was observed even when the same inoculum was used (differences up to 4-fold dilutions). Heteroresistance was suspected due to the presence of colonies in the Etest inhibition zone. It was confirmed by population analysis profiles of 4 isolates displaying different imipenem MICs, with the exception of an OmpK36-porin-deficient isolate that homogeneously expressed carbapenem resistance (MIC, >128 mg/liter). Low carbapenem MIC reproducibility could be due to the presence of resistant subpopulations and variable expression of the resistance mechanisms. Since carbapenem MICs are not good markers of MBL production, reliable and reproducible phenotypic methods are needed to detect the presence of this mechanism.

Introduction: Impetigo is the most common bacterial skin infection in children. Treatment is becoming complicated due to the development of antimicrobial resistance, especially in the main pathogen, Staphylococcus aureus. Ozenoxacin, a novel non-fluorinated topical quinolone antimicrobial, has demonstrated efficacy in impetigo. Areas covered: This article reviews the microbiology, pharmacodynamic and pharmacokinetic properties of ozenoxacin, and its clinical and microbiological efficacy in impetigo. Expert opinion: In an environment of increasing antimicrobial resistance and concurrent slowdown in antimicrobial development, the introduction of a new agent is a major event. Ozenoxacin is characterized by simultaneous affinity for DNA gyrase and topoisomerase IV, appears to be impervious to certain efflux pumps that confer bacterial resistance to other quinolones, shows low selection of resistant mutants, and has a mutant prevention concentration below its concentration in skin. These mechanisms protect ozenoxacin against development of resistance, while the absence of a fluorine atom in its structure confers a better safety profile versus fluoroquinolones. In vitro studies have demonstrated high potency of ozenoxacin against staphylococci and streptococci including resistant strains of S. aureus. Clinical trials of ozenoxacin in patients with impetigo reported high clinical and microbiological success rates. Preserving the activity and availability of ozenoxacin through antimicrobial stewardship is paramount.