Comparative in vitro activity of Meropenem, Imipenem and Piperacillin/tazobactam against 1071 clinical isolates using 2 different methods: a French multicentre study.

BACKGROUND: Meropenem is a carbapenem that has an excellent activity against many gram-positive and gram-negative aerobic, facultative, and anaerobic bacteria. The major objective of the present study was to assess the in vitro activity of meropenem compared to imipenem and piperacillin/tazobactam, against 1071 non-repetitive isolates collected from patients with bacteremia (55%), pneumonia (29%), peritonitis (12%) and wound infections (3%), in 15 French hospitals in 2006. The secondary aim of the study was to compare the results of routinely testings and those obtained by a referent laboratory. METHOD: Susceptibility testing and Minimum Inhibitory Concentrations (MICs) of meropenem, imipenem and piperacillin/tazobactam were determined locally by Etest method. Susceptibility to meropenem was confirmed at a central laboratory by disc diffusion method and MICs determined by agar dilution method for meropenem, imipenem and piperacillin/tazobactam. RESULTS: Cumulative susceptibility rates against Escherichia coli were, meropenem and imipenem: 100% and piperacillin/tazobactam: 90%. Against other Enterobacteriaceae, the rates were meropenem: 99%, imipenem: 98% and piperacillin/tazobactam: 90%. All Staphylococci, Streptococci and anaerobes were susceptible to the three antibiotics. Against non fermeters, meropenem was active on 84-94% of the strains, imipenem on 84-98% of the strains and piperacillin/tazobactam on 90-100% of the strains. CONCLUSIONS: Compared to imipenem, meropenem displays lower MICs against Enterobacteriaceae, Escherichia coli and Pseudomonas aeruginosa. Except for non fermenters, MICs90 of carbapenems were <4 mg/L. Piperacillin/tazobactam was less active against Enterobacteriaceae and Acinetobacter but not P. aeruginosa. Some discrepancies were noted between MICs determined by Etest accross centres and MICs determined by agar dilution method at the central laboratory. Discrepancies were more common for imipenem testing and more frequently related to a few centres. Overall MICs determined by Etest were in general higher (0.5 log to 1 log fold) than MICs by agar dilution.

Factors determining length of the postoperative hospital stay after major head and neck cancer surgery.

Hospital stays constitute the main component of costs of cancer treatment. We conducted a prospective study to identify the determinants of the length of stay (LOS) after head and neck cancer surgery (HNCS). Patients who underwent major HNCS with opening of mucosa and with curative intent were enrolled. Data were collected for patient characteristics, type of tumour, surgical procedures and postoperative outcome. LOS defined as the interval between the day of admission for surgery until hospital discharge or death was determined by the Kaplan-Meier method. Independent determinants of LOS were identified using a Cox model. All 260 patients were included. Median LOS was 26 days (range, 3-178). In the multivariate model, four variables remained associated with increased LOS: American Society of Anaesthesiologist's score equal to 3 (hazard ratio 1.62 [1.23-1.99]), duration of surgical procedure >220 min., (HR=1.37 [1.22-1.56]), SSI (HR=2.09 [2.02-2.54]), occurrence of SSI caused by multi-resistant pathogen (HR=2.92 [2.78-3.77]) and occurrence of PP (HR=2.09 [1.78-2.81]). The present results highlighted the long duration of LOS after head and neck cancer surgery. Two variables (duration of surgical procedure and occurrence of nosocomial infections) were associated with LOS and might be improved by appropriate strategies.

Factors predicting bacterial involvement in severe acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Strategies aiming at reducing antibiotic use are required in the intensive care unit (ICU). Although antibiotic treatment is recommended in patients with severe exacerbation of chronic obstructive pulmonary disease (COPD), a bacterial etiology is found in only a half of these patients. OBJECTIVES: The aim of this study was to determine factors predicting bacterial isolation in severe acute exacerbations of COPD. METHODS: All patients with severe acute exacerbation of COPD requiring intubation and mechanical ventilation were included in this prospective observational cohort study. At ICU admission, information on endotracheal aspirate purulence and hyperthermia was collected. In all patients, Gram stain and quantitative endotracheal aspirate culture (positive at 10(6) cfu/ml) were performed. In addition, leukocyte count, C-reactive protein and procalcitonin (PCT) levels were measured. RESULTS: Ninety-eight severe acute exacerbations of COPD requiring intubation and mechanical ventilation were studied. Forty-nine bacteria were isolated at significant threshold in 40 exacerbations. Streptococcus pneumoniae (16%), methicillin-sensitive Staphylococcus aureus (16%) and Hemophilus influenzae (14%) were the most frequently isolated bacteria. PCT >0.5 ng/ml and positive Gram stain of endotracheal aspirate were independently associated with bacterial isolation in severe acute exacerbation of COPD. Positive Gram stain and PCT >0.5 ng/ml had a negative predictive value >95%. Similar results were found after excluding patients with prior antibiotic treatment. CONCLUSION: Positive Gram stain of endotracheal aspirate and PCT >0.5 ng/ml are independently associated with bacterial isolation in severe acute exacerbation of COPD. These results could be helpful for future interventional studies aiming at reducing antibiotic use in these patients.

Impact of antifungal treatment on Candida-Pseudomonas interaction: a preliminary retrospective case-control study.

OBJECTIVE: A pathogenic interaction between Candida albicans and Pseudomonas aeruginosa has recently been demonstrated. In addition, experimental and clinical studies identified Candida spp. tracheobronchial colonization as a risk factor for P. aeruginosa pneumonia. The aim of this study was to determine the impact of antifungal treatment on ventilator-associated pneumonia (VAP) or tracheobronchial colonization due to P. aeruginosa. DESIGN AND SETTING: Retrospective observational case-control study conducted in a 30-bed ICU during a 1-year period. PATIENTS AND METHODS: One hundred and two patients intubated and ventilated for longer than 48 h with tracheobronchial colonization by Candida spp. Routine screening for Candida spp. and P. aeruginosa was performed at ICU admission and weekly. Antifungal treatment was based on medical staff decisions. Patients with P. aeruginosa VAP or tracheobronchial colonization were matched (1:2) with patients without P. aeruginosa VAP or tracheobronchial colonization. In case and control patients, risk factors for P. aeruginosa VAP or tracheobronchial colonization were determined using univariate and multivariate analyses. RESULTS: Thirty-six patients (35%) received antifungal treatment. Nineteen patients (18%) developed a P. aeruginosa VAP or tracheobronchial colonization, and all were successfully matched. Antifungal treatment [31% vs 60%; p=0.037, OR (95% CI)=0.67 (0.45-0.90)], and duration of antifungal treatment (7+/-11 vs 14+/-14 days; p=0.045, in case and control patients respectively) were significantly associated with reduced risk for P. aeruginosa VAP or tracheobronchial colonization. Antifungal treatment was the only variable independently associated with P. aeruginosa VAP or tracheobronchial colonization (OR=0.68, 95% CI=0.49-0.90, p=0.046). CONCLUSION: In patients with Candida spp. tracheobronchial colonization, antifungal treatment may be associated with reduced risk for P. aeruginosa VAP or tracheobronchial colonization.

Antimicrobial resistance data on 16,756 Streptococcus pneumoniae isolates in 1999: A Pan-Regional Multicenter Surveillance Study in France.

The rising prevalence of antibiotic-resistant Streptococcus pneumoniae is a phenomenon observed to different degrees around the world. The present national surveillance study report analyzes a total of 16,756 strains of S. pneumoniae collected across France in 1999. The overall prevalence of S. pneumoniae with decreased susceptibility to penicillin was 44%, to amoxicillin 26%, and to cefotaxime 17%. The proportion of high-level resistant strains to penicillin (MIC > 1 mg/L), amoxicillin and cefotaxime (MIC > 2 mg/L) remained low: 12.3%, 1.8%, and 0.4% respectively. Prevalence of resistance to other antibiotics was high: 53% to erythromycin, 41.7% to cotrimoxazole, 31.8% to tetracycline, and 24.6% to chloramphenicol. Prevalence of penicillin-resistant S. pneumoniae varied according to subject age and specimen source. It was higher in children (52.7%) than in adults (39.8%) and higher in strains isolated from middle ear fluid (63.6%) than from blood cultures (41.8%) in children. S. pneumoniae resistant to other antibiotics were more common in children than in adults, although figures showed geographical variations. Comparison with a previous study realized in 1997 in the same regions confirms a rising trend in the prevalence of resistant bacteria. Therefore, we conclude that prevalence of antibiotic-resistant S. pneumoniae in 1999 continued to rise in France, although strains with high-level resistance to penicillin remained stable.

Direct microscopic examination of imprints in patients undergoing cardiac valve replacement.

BACKGROUND: Bacteriological analysis of cardiac valves might be indicated in patients with suspected endocarditis. METHODS: We report here a prospective study on fifty-three consecutive patients whose native valves were sent to the bacteriological and pathological laboratories, to investigate the performance of direct microscopic examination of imprints and valve culture. RESULTS: On the basis of a histopathological gold standard to classify the inflammatory valve process, the sensitivity, the specificity, the positive and the negative predictive values of direct microscopic examination of imprints and valve culture were 21%, 100%, 100%, 60%, and 21%, 72%, 38%, 52% respectively. This weak threshold of the direct microscopic examination of imprints could be due to antimicrobial therapy prescribed before cardiac surgery and the fact that the patients came from a tertiary hospital receiving patients with a prolonged history of endocarditis. CONCLUSION: Clinical context and histopathology are indispensable when analyzing the imprints and valve culture.

Epidemiology and antimicrobial resistance of Streptococcus pneumoniae in France in 2007: data from the pneumococcus surveillance network.

Antimicrobial resistance of Streptococcus pneumoniae in France is closely monitored by the pneumococcus surveillance network, founded in 1995, which collects data from regional observatories (Observatoire Régionaux du Pneumocoque [ORP]). In 2007, 23 ORPs analyzed the antibiotic susceptibility of 5,302 isolates of S. pneumoniae recovered in France from cerebrospinal fluid, blood, middle ear fluid, and pleural fluid, as well as from adult respiratory samples. The study showed that 38.2% of the strains were nonsusceptible to penicillin, 19.3% nonsusceptible to amoxicillin, and 10.5% nonsusceptible to cefotaxime. The percentage of pneumococcus nonsusceptible to penicillin varied according to both the sample and the age of the patient (child/adult): blood (27.8%/32.5%), cerebrospinal fluid (33.7%/34.6%), middle ear fluid (60.2%/27.5%), and pleural fluid (50.0%/31.0%). Between 2003 and 2007, the frequency of penicillin resistance in invasive pneumococcal disease gradually decreased from 46.4% to 29.0% in children and from 43.8% to 32.7% in adults. This decrease coincided with the introduction of a seven-valent pneumococcal conjugate vaccine into immunization programs and with a general reduction in levels of antibiotic consumption in France.

Daily serum piperacillin monitoring is advisable in critically ill patients.

The aim of the present study was to evaluate the benefit of monitoring serum piperacillin concentrations in critically ill patients. This was an 11-month, prospective, observational study in a 30-bed Intensive Care Unit in a teaching hospital, involving 24 critically ill patients with evidence of bacterial sepsis. All patients received a 66 mg/kg intravenous bolus of piperacillin in combination with tazobactam (ratio 1:0.125) followed by continuous infusion of 200mg/kg/24h. The dosage was adjusted when the serum piperacillin concentration either fell below 4x the drug's minimum inhibitory concentration (MIC) for the causative agent or exceeded the toxic threshold of 150 mg/L. With the initial regimen, serum piperacillin concentrations were within the therapeutic target range in only 50.0% of patients (n=12). This proportion increased to 75.0% (18 patients) (P=0.006) following dosage adjustment. For patients with low initial serum piperacillin concentrations (n=8), the percentage of time during which the concentration remained above 4x MIC (%T>4x MIC) was 7.1+/-5.9% before dosage adjustment and 27.3+/-8.6% afterwards. In conclusion, in critically ill patients, monitoring and adjustment of serum piperacillin levels is required to prevent overdosing and might also help to correct underdosing, an important cause of antibiotic therapy failure.

Serotype distribution and antibiotic resistance of Streptococcus pneumoniae strains isolated from adults in France: evolution between 2001 and 2003.

Antibiotic-resistant Streptococcus pneumoniae (Sp) are described around the world. The present national surveillance study report analyzes more than 6000 Sp strains, isolated from adults across France in 2001 and 2003, from blood cultures (3086 in 2001 and 3164 in 2003), cerebrospinal fluid (respectively, 238 and 240), or middle ear fluid (respectively, 110 and 100). The proportion of isolates with reduced susceptibility to penicillin fell significantly between 2001 and 2003 from 46.5% to 43.9%. The proportion of high-level resistant strains to penicillin minimal inhibitory concentrations (MIC > 1 mg/L), amoxicillin, and cefotaxime (MIC > 2 mg/L) slightly decreased but remained low: 10.6%, 1.2%, and 0.2% in 2003. Resistance to other antibiotics (erythromycin, cotrimoxazole, tetracycline, and chloramphenicol) also decreased. Decrease in prevalence of penicillin-resistant Sp varied according to specimen source. The proportion of penicillin nonsusceptible pneumococci decreased in blood cultures and middle ear fluids between 2001 and 2003 but increased in cerebrospinal fluid (43.4% and 46.5%, respectively). Serotypes covered by the heptavalent vaccine accounted for 42.4% of all isolates recovered in 2001 and 46.1% in 2003. Prevalence of antibiotic-resistant Sp decreased in 2003 in France.

Risk factors for relapse of ventilator-associated pneumonia related to nonfermenting Gram negative bacilli: a case-control study.

BACKGROUND: The aim of this study was to determine risk factors for relapse of ventilator-associated pneumonia (VAP) related to nonfermenting Gram negative bacilli (NF-GNB). METHODS: This is a retrospective case-control study based on prospectively collected data. Two hundred and seventy six patients with monobacterial VAP related to NF-GNB were eligible. Patients with subsequent superinfection or persistent pulmonary infection were excluded. Patients with relapse of NF-GNB VAP were matched (1:2) with patients without relapse. Matching criteria included the duration of mechanical ventilation before VAP relapse, age+/-5 years, SAPS II at ICU admission+/-5, and the date of admission. Univariate and multivariate analyses were used to determine risk factors for relapse of NF-GNB VAP in cases and controls. RESULTS: Thirty (10%) patients developed a relapse of NF-GNB VAP, 27 (90%) patients were successfully matched with 54 controls. Inappropriate initial antibiotic treatment was the only variable independently associated with relapse of VAP related to NF-GNB (OR [95% CI]=8.1 [2-33], p=0.003). Although ICU-mortality rate was similar in cases and controls (55% vs 72%, p=0.132), the duration of mechanical ventilation and ICU stay were significantly higher in cases than in controls. CONCLUSION: Inappropriate initial antibiotic treatment is independently associated with relapse of VAP related to NF-GNB.

Pseudomonas aeruginosa may accumulate drug resistance mechanisms without losing its ability to cause bloodstream infections.

In this study, we systematically investigated the resistance mechanisms to beta-lactams, aminoglycosides, and fluoroquinolones of 120 bacteremic strains of Pseudomonas aeruginosa. Pulsed-field gel electrophoresis genotyping showed that 97 of these strains were represented by a single isolate, 10 by 2 and 1 by 3 clonally related isolates, respectively. Seventy-five percent (90 out of 120) of the bacteremic P. aeruginosa strains displayed a significant resistance to one or more of the tested antimicrobials (up to 11 for 1 strain). These strains were found to harbor a great diversity of resistance mechanisms (up to 7 in 1 strain), leading to various levels of drug resistance. Interestingly, 11 and 36% of the isolates appeared to overproduce the MexAB-OprM and MexXY-OprM efflux systems, respectively. Altogether, our results show that P. aeruginosa may accumulate intrinsic (overproduction of cephalosporinase AmpC, increased drug efflux, fluoroquinolone target mutations, and deficient production of porin OprD) and exogenous (production of secondary beta-lactamases and aminoglycoside-modifying enzymes) resistance mechanisms without losing its ability to generate severe bloodstream infections. Consequently, clinicians should be aware that multidrug-resistant P. aeruginosa may remain fully pathogenic.

Multiple-drug-resistant bacteria in patients with severe acute exacerbation of chronic obstructive pulmonary disease: Prevalence, risk factors, and outcome.

OBJECTIVE: To determine prevalence, risk factors, and effect on outcome of multiple-drug-resistant (MDR) bacteria in patients with severe acute exacerbation of chronic obstructive pulmonary disease. DESIGN: Prospective, observational, cohort study. SETTING: Thirty-bed medical intensive care unit (ICU) in a university hospital. METHODS: All chronic obstructive pulmonary disease patients with acute exacerbation who required intubation and mechanical ventilation for >48 hrs were eligible during a 4-yr period. Patients with pneumonia or other causes of acute respiratory failure were not eligible. In all patients, quantitative tracheal aspirate was performed at ICU admission (positive at 10 colony-forming units [cfu]/mL). MDR bacteria were defined as methicillin-resistant Staphylococcus aureus, ceftazidime- or imipenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, and extended-spectrum beta-lactamase-producing Gram-negative bacilli. All patients received empirical antibiotic treatment at ICU admission. Univariate and multivariate analyses were used to determine variables associated with MDR bacteria and variables associated with ICU mortality. RESULTS: A total of 857 patients were included, and 304 bacteria were isolated (>/=10 cfu/mL) in 260 patients (30%), including 75 MDR bacteria (24%) in 69 patients (8%). When patients with MDR bacteria were compared with patients without MDR bacteria, previous antimicrobial treatment (odds ratio [OR], 2.4; 95% confidence interval [95% CI], 1.2-4.7; p = .013) and previous intubation (OR, 31; 95% CI, 12-82; p < .001) were independently associated with MDR bacteria. When patients with bacteria other than MDR or patients with no bacteria were used as a reference group, these risk factors were still independently associated with MDR bacteria. Although ICU mortality rate was higher in patients with MDR bacteria than in patients without MDR bacteria (44% vs. 25%; p = .001; OR, 2.3; 95% CI, 1.4-3.8), MDR bacteria were not independently associated with ICU mortality. Inappropriate initial antibiotic treatment (88% vs. 5%; p = <.001; OR, 6.7; 95% CI, 3.8-12) and ventilator-associated pneumonia (23% vs. 5%; p = <.001; OR, 1.3; 95% CI, 1-1.8) rates were significantly higher in patients with MDR bacteria than in patients with bacteria other than MDR. Inappropriate initial antibiotic treatment was independently associated with increased ICU mortality (OR, 7.1; 95% CI, 1.9-30; p = .003). CONCLUSION: MDR bacteria are common in patients with acute exacerbation of chronic obstructive pulmonary disease requiring intubation and mechanical ventilation. Previous antimicrobial treatment and previous intubation are independent risk factors for MDR bacteria. Although MDR bacteria are not independently associated with ICU mortality, inappropriate initial antibiotic treatment is an independent risk factor for ICU mortality in these patients. Further studies are needed to determine whether broad-spectrum antibiotic treatment is cost-effective in these patients.

First-generation fluoroquinolone use and subsequent emergence of multiple drug-resistant bacteria in the intensive care unit.

OBJECTIVE: The objective of this study was to determine the relationship between fluoroquinolone (FQ) use and subsequent emergence of multiple drug-resistant bacteria (MRB) in the intensive care unit (ICU). DESIGN: The authors conducted a prospective observational cohort study and a case control study. SETTING: The study was conducted in a 30-bed ICU. METHODS: All immunocompetent patients hospitalized for >48 hrs who did not receive antibiotics before ICU admission were eligible during a 15-month period. Routine MRB screening was performed at ICU admission and weekly thereafter. This screening included tracheal aspirate and nasal, anal, and axilla swabs. Univariate and multivariate analyses were used to determine risk factors for MRB emergence in the ICU. In addition, a case control study was performed to determine whether FQ use is associated with subsequent emergence of MRB. RESULTS: Two hundred thirty-nine patients were included; 108 ICU-acquired MRB were isolated in 77 patients. FQ use and longer duration of antibiotic treatment were identified as independent risk factors for MRB occurrence (odds ratio [95% confidence interval [CI] = 3.3 [1.7-6.5], 1.1 [1.0-1.2]; p < .001; respectively). One hundred thirty-five (56%) patients received FQ; matching was successful for 72 (53%) of them. Number of MRB (40 vs. 15 per 1,000 ICU days; p = .019) and percentage of patients with MRB (40% vs. 22%; OR [95% CI] = 1.5 [1.0-2.4]; p = .028) were significantly higher in cases than in controls. Although methicillin-resistant Staphylococcus aureus (26% vs. 12%; OR [95% CI] = 1.6 [.6-2.9]; p = .028) and extending-spectrum beta-lactamase-producing Gram-negative bacilli (11% vs. 1%; OR [95% CI] = 4.7 [0.7-30.2]; p = .017) rates were higher in cases than in controls, ceftazidime or imipenem-resistant Pseudomonas aeruginosa (15% vs. 8%), Acinetobacter baumannii (1% vs. 5%), and Stenotrophomonas maltophilia (2% vs. 1%) rates were similar (p > .05) in case and control patients. CONCLUSION: FQ use and longer duration of antibiotic treatment are independently associated with MRB emergence. Reducing antimicrobial treatment duration and restricting FQ use could be suggested to control MRB spread in the ICU.

Effect of gingival and dental plaque antiseptic decontamination on nosocomial infections acquired in the intensive care unit: a double-blind placebo-controlled multicenter study.

OBJECTIVE: To document the effect of gingival and dental plaque antiseptic decontamination on the rate of nosocomial bacteremias and respiratory infections acquired in the intensive care unit (ICU). DESIGN: Prospective, multicenter, double-blind, placebo-controlled efficacy study. SETTING: Six ICUs: three in university hospitals and three in general hospitals. PATIENTS: A total of 228 nonedentulous patients requiring endotracheal intubation and mechanical ventilation, with an anticipated length of stay > or =5 days. INTERVENTIONS: Antiseptic decontamination of gingival and dental plaque with a 0.2% chlorhexidine gel or a placebo gel, three times a day, during the entire ICU stay. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical characteristics, organ function data (Logistic Organ Dysfunction score), severity of condition (Simplified Acute Physiologic Score), and dental plaque status were assessed at baseline and until 28 days. Bacteriologic sampling of dental plaque and saliva was done every 5 days, and blood, tracheal aspirate, and bronchoalveolar lavage cultures were performed when appropriate. The primary efficacy end point was the incidence of bacteremia, bronchitis, and ventilator-associated pneumonia, expressed as a percentage and per 1000 ICU days. All baseline characteristics were similar between the treated and the placebo groups. The incidence of nosocomial infections was 17.5% (13.2 per 1000 ICU days) in the placebo group and 18.4% (13.3 per 1000 ICU days) in the plaque antiseptic decontamination group (not significant). No difference was observed in the incidence of ventilator-associated pneumonia per ventilator or intubation days, mortality, length of stay, and care loads (secondary end points). On day 10, the number of positive dental plaque cultures was significantly lower in the treated group (29% vs. 66%; p < .05). Highly resistant Pseudomonas, Acinetobacter, and Enterobacter species identified in late-onset ventilator-associated pneumonia and previously cultured from dental plaque were not eradicated by the antiseptic decontamination. No side effect was reported. CONCLUSIONS: Gingival and dental plaque antiseptic decontamination significantly decreased the oropharyngeal colonization by aerobic pathogens in ventilated patients. However, its efficacy was insufficient to reduce the incidence of respiratory infections due to multiresistant bacteria.

Previous chemotherapy as a predictor of wound infections in nonmajor head and neck surgery: Results of a prospective study.

BACKGROUND: The goal of this prospective study was to determine the incidence of wound infections (WI) after clean uncontaminated head and neck cancer procedures and after emergency tracheotomies. METHODS: Two hundred twelve clean procedures without tracheotomy or opening of mucosa (neck dissections, large skin resections, thyroidectomies, parotid gland resections, and explorative cervicotomies) were studied at Oscar Lambret Cancer Center over a 24-month period. RESULTS: WI rate was 6.6% (14 of 212). In a univariate analysis, only one variable was significantly related to the likelihood of WI: previous anticancer chemotherapy. All but one patient who had had previous chemotherapy demonstrated WI (14 of 15). CONCLUSIONS: After previous chemotherapy, WI rate in clean uncontaminated head and neck surgery was as high as 90%. In this case, antibiotic prophylaxis should be evaluated.

Bactericidal activity of three beta-lactams alone or in combination with a beta-lactamase inhibitor and two aminoglycosides against Klebsiella pneumoniae harboring extended-spectrum beta-lactamases.

OBJECTIVE: To study the bactericidal activity of beta-lactam antibiotics (imipenem, cefepime, cefpirome) alone or in combination with a beta-lactamase inhibitor (sulbactam) in the presence or absence of aminoglycoside (amikacin or isepamicin) against Klebsiella pneumoniae strains producing extended-spectrum beta-lactamases (ESBLs). METHODS: We characterized 10 strains by means of analytic isoelectric focusing and pulsed-field gel electrophoresis. The ESBLs produced by these strains were derived from either TEM (TEM-1, TEM-2) or SHV-1. The killing-curve method was used for this bacterial investigation. Bacteria (final inoculum 5x105 CFU/mL) were incubated with antibiotics at clinical concentrations obtained in vivo. RESULTS: All the combinations with cefepime or cefpirome + sulbactam were bactericidal, with a 4 log10 decrease being obtained within 6 h without regrowth at 24 h, whereas imipenem alone, and combinations, gave a bactericidal effect within 6 h. The two cephalosporins alone decreased the inoculum of 4 log10 at 6 h but regrowth was observed at 24 h. When the aminoglycoside was added, this bactericidal effect was obtained within 3 h with amikacin and within 1 h with isepamicin. CONCLUSIONS: Cefepime + sulbactam or cefpirome + sulbactam may be an alternative to imipenem for the treatment of patients with ESBL-producing K. pneumoniae. Aminoglycosides are often associated in nosocomial infections due to ESBL-producing K. pneumoniae: isepamicin acted faster than amikacin, but both worked well. To conclude, it may be prudent to avoid extended-spectrum cephalosporins as single agent when treating serious infections due to ESBL-producing K. pneumoniae. Addition of a beta-lactamase inhibitor such as sulbactam +/- aminoglycoside is advisable to avoid failure of treatment.

Prognostic significance of wound infections following major head and neck cancer surgery: an open non-comparative prospective study.

OBJECTIVE: We evaluated the incidence, risk factors and consequences of wound infection (WI) following major head and neck cancer surgery in an open non-comparative study. PATIENTS AND METHODS: The study group, comprising 95 patients who underwent clean-contaminated procedures with opening of the upper aerodigestive tract for biopsy-proven squamous cell cancer, were studied over a 1-year period. Antibiotic prophylaxis was amoxicillin and clavulanic acid. More than 20 variables were prospectively recorded for each patient. The mean follow-up was 30 months. MAIN RESULTS: The overall WI rate was 50.5% (48/95). Most pathogens isolated from samples were gram-negative rods. In univariate analysis, we found three risk factors for WI: alcohol consumption (P = 0.07), a hypopharyngeal location (P = 0.02) and laryngectomy stoma (P = 0.01). WI were associated with postoperative fever (P = l.5 x 10(-11)), postoperative antibiotic therapy (P = 1.5 x 10(-5)) and postoperative death (P = 0.043). Patients without WI had a median postoperative hospital stay of 15 days compared with 29 days for those with WI (P < 0.001). Healing of WI was achieved after a median time of 48 days. WI delayed postoperative radiation therapy in 21 out of 33 evaluable patients. But overall survival, and local and metastatic failures were similar with and without WI. CONCLUSIONS: WI are associated with a heavy postoperative morbidity, but have no prognostic impact on cancer control.

Haemophilus influenzae carriage in children attending French day care centers: a molecular epidemiological study.

The nasopharyngeal Haemophilus influenzae flora of healthy children under the age of 3 years attending day care centers in three distinct French geographic areas was analyzed by sampling during two periods, spring 1999 (May and June) and fall 1999 (November and December). The average carrier rate among 1,683 children was 40.9%. The prevalence of capsulated H. influenzae carriers was 0.4% for type f and 0.6% for type e. No type b strains were found among these children, of whom 98.5% had received one or more doses of anti-Haemophilus b vaccine. Among the strains, 44.5% were TEM-type beta-lactamase producers and nine (1.3%) were beta-lactamase-negative ampicillin-resistant strains. Pulsed-field gel electrophoresis restriction patterns showed a large diversity with 366 SmaI patterns from 663 strains. Among the strains isolated during a given period, 33% were isolated simultaneously in more than one area. In each area, depending on the sampling period, 68 to 72% of the strains had new pulsotypes and persistence of 28 to 32% of the strains was noted. For the 297 beta-lactamase-producing strains, 194 patterns were found. The genomic diversity of these strains was comparable to that of the whole set of strains and does not suggest a clonal diffusion. Among the beta-lactamase-producing strains isolated in November and December, depending on the area, 66 to 73% had new pulsotypes with persistence of only 27 to 33% of the strains. In any given geographic area, colonization by H. influenzae appears to be a dynamic process involving a high degree of genomic heterogeneity among the noncapsulated colonizing strains.