In Vitro and In Vivo Activity of Amoxicillin-Clavulanate Combined with Ceftibuten or Cefpodoxime Against Extended-Spectrum ß-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae.

Infections due to extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales are an increasingly common problem. For many of these infections, no oral treatment options are available. The activity of amoxicillin-clavulanate combined with ceftibuten or cefpodoxime was evaluated against a group of Escherichia coli and Klebsiella pneumoniae clinical isolates possessing a variety of CTX-M- and SHV-type ESBLs; some possessed blaTEM1 as well. In time-kill studies, the combination of subinhibitory concentrations of amoxicillin-clavulanate with ceftibuten was bactericidal and synergistic for all strains with an amoxicillin-clavulanate MIC ≤32 µg/mL, regardless of the type of ESBL and the cephalosporin minimal inhibitory concentration (MIC). The combination with cefpodoxime was also bactericidal and synergistic against all but one of these strains. These combinations were further tested against two strains of K. pneumoniae and one E. coli in a sepsis model using Galleria mellonella larvae. The combination of amoxicillin-clavulanate with ceftibuten demonstrated a synergistic survival benefit against all three strains. The combination with cefpodoxime also improved survival against the two K. pneumoniae strains, but not the E. coli strain. These findings support combining amoxicillin-clavulanate with ceftibuten, and possibly cefpodoxime, for the treatment of infections due to ESBL producers and suggest that having an amoxicillin-clavulanate MIC of 32 µg/mL or less may predict activity at clinically achievable concentrations. Clinical studies are warranted to further evaluate this therapeutic approach.

Molecular epidemiology of a citywide outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae infection.

Multidrug-resistant strains of Klebsiella pneumoniae are a problem in many hospitals. In 1999, the molecular epidemiology of K. pneumoniae with extended-spectrum beta-lactamases (ESBLs) was studied at 15 hospitals in Brooklyn. Of 824 unique patient isolates, 34% were presumptive ESBL producers. Of this subset, 34% were susceptible to cefoxitin, 42% to ciprofloxacin, 48% to ceftriaxone, 55% to piperacillin-tazobactam, 57% to amikacin, and 86% to cefepime. Ribotype analysis revealed 87 unique types. However, 2 clusters accounted for 35% of isolates and were present in most of the hospitals. One cluster was significantly more resistant to most antibiotics. Although there was a predominance of SHV-5, considerable heterogeneity of beta-lactamases was evident, even among isolates of the same cluster. A correlation was found between the use of cephalosporins and the prevalence of ESBL-producing strains of K. pneumoniae at each hospital. Our data suggest that there is an advanced outbreak of multidrug-resistant K. pneumonia infection that is affecting all Brooklyn hospitals.

Citywide clonal outbreak of multiresistant Acinetobacter baumannii and Pseudomonas aeruginosa in Brooklyn, NY: the preantibiotic era has returned.

BACKGROUND: Carbapenems are important agents for treating nosocomial gram-negative infections. Carbapenem-resistant bacteria have become increasingly problematic in certain regions. This study determined the citywide prevalence and molecular epidemiological features of carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa in Brooklyn, NY. METHODS: All unique patient isolates of A baumannii and P aeruginosa were collected from 15 Brooklyn hospitals from July 1, 1999, through September 30, 1999. Antibiotic susceptibilities, the genetic relatedness of resistant isolates, and the relationship between antibiotic use and resistance rates were determined. RESULTS: A total of 419 isolates of A baumannii and 823 isolates of P aeruginosa were collected. For A baumannii, 53% were resistant to meropenem and/or imipenem, and 12% were resistant to all standard antibiotics. Ribotyping revealed that a single clone accounted for 62% of the samples and was isolated from patients at all 15 hospitals. The rate of carbapenem resistance was associated with cephalosporin use at each hospital (P =.004). For P aeruginosa, 24% were resistant to imipenem, 5% to amikacin, and 15% to 29% to other antipseudomonal agents. Ribotyping revealed that 3 clones accounted for nearly half of the isolates and were shared by most hospitals. CONCLUSIONS: Approximately 400 patients were infected or colonized with carbapenem-resistant A baumannii and P aeruginosa during a 3-month period in 1999. A few strains have spread widely throughout hospitals in this region. The prevalence of resistant A baumannii seems to be correlated with cephalosporin use. Multiresistant hospital-acquired bacteria should be viewed as a serious public health issue rather than an individual hospital's problem. An intensive coordinated effort will be needed to effectively address this problem.