In vitro generation of mutants of Klebsiella pneumoniae following exposure to fluorquinolones. Relationship with the presence of extended spectrum betalactamases

O. Noguera ,  J. C. Rodríguez ,  R. Cremades ,  M. Ruiz ,  G. Royo 

In order to provide data that may help to explain the relationship between production of extended spectrum betalactamases and fluorquinolone resistance in Klebsiella pneumoniae, we have developed an in vitro model of exposure to sub-inhibitory concentrations of various fluorquinolones (ciprofloxacin, levofloxacin and moxifloxacin) in two strains, one of which is a producer of extended spectrum betalactamases (ESBL). Our data show that mutants with reduced fluorquinolone susceptibility appear in both cases, but that they appear earlier in ESBL-producing strains (13.3 days versus 14.4 days), especially following exposure to ciprofloxacin (12.5 days versus 14.9 days for levofloxacin and 14.2 days for moxifloxacin). Therefore, our data help explain the greater fluorquinolone resistance in ESBL-producing strains and confirm the need to administer the correct doses of fluoroquinolones, especially in the case of ciprofloxacin, in order to prevent the emergence of resistant mutants. This is particularly important if the strain is an ESBL-producer.

Key words:  Klebsiella pneumoniae. Fluorquinolones. ESBL. Ciprofloxacin. Levofloxacin.

Rev Esp Quimioter 2008;21(3):180-183 [pdf]    

Evolution of antimicrobial susceptibility patterns of aerobic and facultative gram-negative bacilli causing intra-abdominal infections: results from the SMART studies 2003-2007

M. Guembe ,  E. Cercenado ,  L. Alcalá ,  M. Marín ,  R. Insa ,  E. Bouza 

Study for Monitoring Antimicrobial Resistance Trends (SMART) is an ongoing global antimicrobial surveillance program focused on clinical isolates from intra-abdominal infections (IAI). The objective of this subanalysis was to assess the evolution of the antimicrobial susceptibility patterns among aerobic and facultative gram-negative bacilli (GNB) recovered over a 5-year period at our institution. We tested the in vitro activity of the antimicrobials, commonly used to treat IAI, against consecutive unique isolates from IAI using microdilution techniques according to the CLSI guidelines for MIC testing. All isolates were screened phenotypically for extended-spectrum beta-lactamase (ESBL) production. Isolates recovered within 48 h of hospitalization were considered community-acquired (CA). Over the study period a total of 572 aerobic and facultative gram-negative bacilli were recovered from 510 patients, of which 258 (45%) were CA. Enterobacteriaceae composed 91% of the total isolates. Escherichia coli was the most common isolated species (52%). Susceptibility rates of Enterobacteriaceae ranged from 96.5 %-100 % to ertapenem, 96.5 %-100 % to imipenem, 87.7%-94.3% to piperacillin-tazobactam, 85.1%-94.3% to cefotaxime, 89.5%-100% to cefepime, 76.3%-84.8% to ciprofloxacin, and 93.8%-100% to amikacin. ESBL were detected in 6.3% of E. coli, 5.7% of Klebsiella spp. and 2.7% of Enterobacter spp. ESBL producers generally had a more antibiotic- resistant profile than non-ESBL producers and 16% of them were CA. Susceptibility rates to ertapenem, imipenem, piperacillin-tazobactam, ceftazidime, cefepime, ciprofloxacin and amikacin were, respectively, for P. aeruginosa: 28.2 %, 58.9%, 82%, 84.6 %, 76.9 %, 71.8% and 82%; for Acinetobacter baumannii: 33.3 %, 100 %, 66.6 %, 66.6 %, 66.6%, 66.6% y 66.6%, and for Stenotrophomonas maltophilia: 0%, 0%, 0%, 28.6%, 0%, 42.9% and 14.3%. Over the 5 year-study period we have not observed significant increases in resistance of aerobic and facultative GNB causing IAI to commonly used beta-lactam antimicrobial drugs. A minority of ESBL-producing Enterobacteriaceae were CA. Carbapenems, including group I agents like ertapenem, were the most reliably active drugs in vitro against isolates producing IAI.

Key words: Intra-abdominal infections. Extended-spectrum beta-lactamases (ESBL). Carbapenems. Antimicrobial resistance.

Rev Esp Quimioter 2008;21(3):166-173   [pdf] 

Bacteremia after periodontal procedures

J. R. Maestre Vera ,  M. Mateo Mestre ,  P. Sánchez Santana 

Introduction. Bacteremia frequently occurs after oral surgery and odontology procedures. Periodontitis may affect the incidence and bacterial spectrum of bacteremia. Periodontal disease may be a significant risk factor for the development of certain systemic diseases. This study has aimed to evaluate the frequency of aerobic and anaerobic bacteria in the bloodstream following scaling and root planing.

Material and methods. Thirteen patients with generalized chronic periodontitis were included in the study. Two samples of peripheral blood were drawn for culture at different times: pre-treatment and immediately after odontology treatment (full-mouth scaling).

Results. None of the 13 patients had bacteremia before the procedures. Bacteremia after scaling occurred in 10/13 (76.9 %) of periodontitis patients. The anaerobic bacteria (Prevotella spp., Micromonas micros and Fusobacterium nucleatum) were the most predominant microorganism. Conclusions. Our findings suggest that periodontal procedures induce bacteremia and may represent risk of developing systemic complications. The use of antibiotic prophylaxis is crucial for its prevention.

Key words:Bacteremia. Periodontal procedures. Anaerobic bacteria. Antibiotic prophylaxis.

Rev Esp Quimioter 2008;21(3):153-156  [pdf]

Obtain best usage of meropenem dose in severe infections. Results of an observational multicenter study

B. Álvarez-Sánchez ,  F. Álvarez-Lerma ,  J. L. Romero ,  L. Fernández Quero ,  F. Ruiz Ferrón ,  H. Sancho Ruiz   

Objective. To describe the effectiveness and tolerability of the dose adjustment of meropenem in empirical treatment of nosocomial infections in critically-ill patients admitted to intensive care medicine services.

Methods. Prospective, observational and multicenter study in patients admitted to 17 intensive care medicine services with nosocomial infection, who were initially treated with meropenem, 1 g every 8 h, were eligible. The initial dose was adjusted to 0.5 g every 8 h if there were: a) a favorable clinical course, and b) microbiological isolation of meropenem-susceptible pathogens or absence of pathogens in cultures.

Results. Ninety-two patients in whom meropenem doses were adjusted to 0.5 g every 8 h were included. Ventilator-associated pneumonia followed by bacteremia was the most frequently treated infections. Microbiological studies were positive in 53 patients, with a predominance of gram-positive bacteria (53.7%), especially methicillin-susceptible Staphylococcus aureus, followed by gram-negative bacteria (42.7 %). A total of 18 patients were not evaluable at the end of treatment. Sixty-seven (90.5 %) of the 74 evaluable patients had a favorable clinical course (54 patients cured and 13 improved). In 50 out of 53 microbiologically evaluable cases, eradication or apparent eradication of initial microorganisms was achieved. In 3 cases, the initial pathogen persisted: Acinetobacter baumannii (2 cases) and Pseudomonas aeruginosa (1 case). On three occasions, new pathogens developed during treatment: A. baumannii (2 cases) and methicillin-resistant S. aureus (1 case). Adverse events occurred in 3 patients (4%), none of which was considered severe, and withdrawal of meropenem was not necessary. A total of 25 (27.2 %) patients died, three of them in relation to the infectious process.

Conclusions. Dose adjustment of meropenem to 0.5 g every 8 h is a useful tool in the treatment of severe nosocomial infections in patients admitted to services of intensive care medicine except in cases in which causative pathogens are non-fermenting Gram-negative bacteria.  Key words:Meropenem. Severe infections. Therapeutic strategy. Acinetobacter baumannii. Pseudomonas aeruginosa.  

Rev Esp Quimioter 2008;21(3):143-148 [pdf]

Isolation of the first metallo-β-lactamase producing Klebsiella pneumoniae in Lebanon

Z. Daoud ,  E. Hobeika ,  A. Choucair ,  R. Rohban 

Introduction. A 58 year-old man was admitted to the Saint Joseph Hospital-Raymond and Aida Najjar polyclinic in Beirut on July 17, 2007 to undergo surgery for a moderately differentiated colonic adenocarcinoma (T3N0). Following several discharges and re-admissions, an extended spectrum beta-lactamase (ESBL) producing Escherichia coli susceptible to imipenem was isolated. The patient was put on imipenem and metronidazole. Three weeks later, imipenem (IMP) resistant Klebsiella pneumoniae was isolated.

Methods and results. The antimicrobial susceptibility profile of the imipenem-resistant Klebsiella pneumoniae strain and related minimum inhibitory concentrations of antibiotics were determined. Hydrolysis of IMP was evaluated and production of metallo-β-lactamase (MBL) was detected by a double disk-synergy test, ethylene diamine tetraacetic

acid (EDTA) inhibited the imipenemase activity, whereas clavulanate and tazobactam did not, this suggesting the production of a metallo-β-lactamase. Isoelectric focusing analysis was performed and indicated the presence of a cefotaximase (blaCTX-M-15). Polymerase chain reaction (PCR) was used and detected the presence of blaIMP-1 and blaCTX-M genes.

Conclusions. During the last decade, many hospital outbreaks caused by ESBL-producing Enterobacteriaceae spp. have been reported in Lebanon. To our knowledge, this is the first report of a clinical isolate of K. pneumoniae producingan MBL in Lebanon.   

Key words: Metallo-β-lactamase. Klebsiella pneumoniae. Extended spectrum beta-lactamase (ESBL). Resistance. Carbapenemases. BlaIMP-1. BlaCTX-M-15. Lebanon.

Rev Esp Quimioter 2008;21(2):123-126 [pdf]