Cefpirome Treatment Results in Limited Selection of Stable Derepressed Enterobacter cloacae Mutants in the Intestinal Flora of Rats Treated for an Experimental Klebsiella pneumoniae Pulmonary Infection.

Background: Fourth-generation cephalosporins have been developed to improve their potency, that is, low minimal inhibitory concentrations (MICs) and to prevent resistance selection of derepressed AmpC-producing mutants in comparison to third-generation cephalosporins as ceftazidime. Objectives: We investigated the role of the administered cefpirome dose on the efficacy of treatment of a Klebsiella pneumoniae lung infection as well as in the selection of resistant Enterobacter cloacae isolates in the intestines of rats treated for a K. pneumoniae lung infection. Materials and Methods: Rats with K. pneumoniae lung infection received therapy with cefpirome doses of 0.4 to 50 mg/kg/day b.i.d. for 18 days. Resistance selection in intestinal E. cloacae was monitored during 43 days. Mutants were checked for ß-lactamase activity, mutations in their structural ampC gene, ampD gene, and omp39-40 gene. Results: A 45% and 100% rat survival rate was obtained by administration of 3.1 and 12.5 mg/kg b.i.d. of cefpirome. A significant correlation was demonstrated in the reduction of the susceptible E. cloacae isolates with %fT>MIC at days 7, 14, 22, and 29. Cefpirome E. cloacae mutants, with increased cefpirome MICs, were obtained in only four rats. Conclusions: The treatment with cefpirome resulted in less selection of derepressed mutants in comparison to ceftazidime as shown by their low number per gram of feces and in a limited number of animals.

PME and Other ESBL-Positive Multiresistant Pseudomonas aeruginosa Isolated from Hospitalized Patients in the Region of Kurdistan, Iraq.

Nosocomial infections occur worldwide and also in the Kurdistan region. Frequently patients colonized with multiresistant Pseudomonas aeruginosa isolates are encountered in many hospitals. As information is lacking with respect to the mechanisms of resistance responsible for the multiresistant character of the P. aeruginosa isolates and their genetic relationship, isolates were prospectively collected and characterized with respect to their mechanism of resistance. During 2012 and 2013, 81 P. aeruginosa isolates were collected from three teaching hospitals in the city of Erbil, Iraq. Susceptibility testing was performed using the VITEK-2 system. Isolates were screened for the presence of extended-spectrum ß-lactamases (ESBLs) and for the presence of metallo ß-lactamases (MBLs). The presence of serine carbapenemases was detected by PCR. The genetic relationship of the isolates was demonstrated by amplified fragment length polymorphism (AFLP). Susceptibility results revealed high rates of resistance against all classes of antibiotics except polymyxins. Genetic characterization demonstrated the presence of ESBL-genes, that is, blaVEB (30%) and blaPER (17%), also ESBL blaPME was detected in four isolates. AFLP typing revealed clonal spread of blaVEB, blaPER, and three clusters of blaOXA-10-positive isolates. Only one isolate was MBL (blaVIM) positive. Of a selected number of isolates (n = 11), whole-genome sequencing analysis revealed that these isolates belonged to "high-risk" MLSTs ST244, ST235, ST308, and ST654. This study reveals the presence and clonal spread of widely resistant high-risk clones of P. aeruginosa in Iraqi Kurdistan. As far as we are aware, this is the first report of multiple, polyclonal, PME producing P. aeruginosa outside the Arabian Peninsula.

The Widespread Presence of a Multidrug-Resistant Escherichia coli ST131 Clade among Community-Associated and Hospitalized Patients.

BACKGROUND & AIMS: The extent of entry of multidrug-resistant Escherichia coli from the community into the hospital and subsequent clonal spread amongst patients is unclear. To investigate the extent and direction of clonal spread of these bacteria within a large teaching hospital, we prospectively genotyped multidrug-resistant E. coli obtained from community- and hospital associated patient groups and compared the distribution of diverse genetic markers. METHODS: A total of 222 E. coli, classified as multi-drug resistant according to national guidelines, were retrieved from both screening (n = 184) and non-screening clinical cultures (n = 38) from outpatients and patients hospitalized for various periods. All isolates were routinely genotyped using an amplified fragment length polymorphism (AFLP) assay and real-time PCR for CTX-M genes. Multi-locus sequence typing was additionally performed to confirm clusters. Based on demographics, patients were categorized into two groups: patients that were not hospitalized or less than 72 hours at time of strain isolation (group I) and patients that were hospitalized for at least 72 hours (group II). RESULTS: Genotyping showed that most multi-drug resistant E. coli either had unique AFLP profiles or grouped in small clusters of maximally 8 isolates. We identified one large ST131 clade comprising 31% of all isolates, containing several AFLP clusters with similar profiles. Although different AFLP clusters were found in the two patient groups, overall genetic heterogeneity was similar (35% vs 28% of isolates containing unique AFLP profiles, respectively). In addition, similar distributions of CTX-M groups, including CTX-M 15 (40% and 44% of isolates in group I and II, respectively) and ST131 (32% and 30% of isolates, respectively) were found. CONCLUSION: We conclude that multi-drug resistant E. coli from the CTX-M 15 associated lineage ST131 are widespread amongst both community- and hospital associated patient groups, with similar genetic diversity and similar distributions of genetic markers.