Skin and soft tissue infections due to Panton-Valentine leukocidin producing Staphylococcus aureus.

OBJECTIVE: The authors had for aim to describe the epidemiological and clinical characteristics, and the treatment of patients presenting with skin and soft tissue infections due to Panton-Valentine leukocidin (PVL) producing Staphylococcus aureus in the Nord-Pas-de-Calais (NPDC) region, North of France. METHODS: We included patients presenting with PVL producing S. aureus infection from seven hospitals in the NPDC region, between February 2004 and April 2008. We retrospectively collected patient data using a standardized questionnaire. The features of patients presenting with skin and soft tissue were then analyzed. RESULTS: PVL producing S. aureus was isolated from 64 patients. Fifty-four patients presented with skin and soft tissue infections. The mean age of patients was 23.8 years (63% male patients). The mean number of persons living with the infected patient was 4.5 (vs. 2.5 in NPDC). The lesions were abscesses with inflammatory signs in 64.8% of the cases (20% were necrotic). Among the patients, 70.3% carried a methicillin resistant strain. Antibiotics per os were used for 83.3% of patients; the first-line antibiotics were considered inadequate in 53.3% of the cases. Among the patients, 83.3% underwent surgery. Fourteen out of 38 patients with available data had been exposed to antibiotic therapy during the three months before hospital management. CONCLUSION: Recent exposure to antibiotics and living with a high number of persons are reasons to suspect a PVL producing S. aureus infection in patients with skin abscess.

In vitro antibacterial activity of ceftobiprole against clinical isolates from French teaching hospitals: proposition of zone diameter breakpoints.

The aims of this study were to determine the in vitro activity profile of ceftobiprole, a pyrrolidinone cephalosporin, against a large number of bacterial pathogens and to propose zone diameter breakpoints for clinical categorisation according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) minimum inhibitory concentration (MIC) breakpoints. MICs of ceftobiprole were determined by broth microdilution against 1548 clinical isolates collected in eight French hospitals. Disk diffusion testing was performed using 30 µg disks according to the method of the Comité de l'Antibiogramme de la Société Française de Microbiologie (CA-SFM). The in vitro activity of ceftobiprole, expressed by MIC(50/90) (MICs for 50% and 90% of the organisms, respectively) (mg/L), was as follows: meticillin-susceptible Staphylococcus aureus, 0.25/0.5; meticillin-resistant S. aureus (MRSA), 1/2; meticillin-susceptible coagulase-negative staphylococci (CoNS), 0.12/0.5; meticillin-resistant CoNS, 1/2; penicillin-susceptible Streptococcus pneumoniae, ≤ 0.008/0.03; penicillin-resistant S. pneumoniae, 0.12/0.5; viridans group streptococci, 0.03/0.12; ß-haemolytic streptococci, ≤ 0.008/0.016; Enterococcus faecalis, 0.25/1; Enterococcus faecium, 64/128; Enterobacteriaceae, 0.06/32; Pseudomonas aeruginosa, 4/16; Acinetobacter baumannii, 0.5/64; Haemophilus influenzae, 0.03/0.12; and Moraxella catarrhalis, 0.25/0.5. According to the regression curve, zone diameter breakpoints could be 28, 26, 24 and 22 mm for MICs of 0.5, 1, 2 and 4 mg/L respectively. In conclusion, this study confirms the potent in vitro activity of ceftobiprole against many Gram-positive bacteria, including MRSA but not E. faecium, whilst maintaining a Gram-negative spectrum similar to the advanced-generation cephalosporins such as cefepime. Thus ceftobiprole appears to be well suited for the empirical treatment of a variety of healthcare-associated infections.

In vitro antibacterial activity of doripenem against clinical isolates from French teaching hospitals: proposition of zone diameter breakpoints.

The aims of the study were to determine the in vitro activity of doripenem, a new carbapenem, against a large number of bacterial pathogens and to propose zone diameter breakpoints for clinical categorization in France according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) minimum inhibitory concentration (MIC) breakpoints. The MICs of doripenem were determined by the broth microdilution method against 1,547 clinical isolates from eight French hospitals. The disk diffusion test was performed (10-µg discs) according to the Comité de l'Antibiogramme de la Société Française de Microbiologie (CASFM) method. The MIC(50/90) (mg/L) values were as follows: methicillin-susceptible Staphylococcus aureus (MSSA) (0.03/0.25), methicillin-resistant Staphylococcus aureus (MRSA) (1/2), methicillin-susceptible coagulase-negative staphylococci (MSCoNS) (0.03/0.12), methicillin-resistant coagulase-negative staphylococci (MRCoNS) (2/8), Streptococcus pneumoniae (0.016/0.25), viridans group streptococci (0.016/2), ß-hemolytic streptococci (≤0.008/≤0.008), Enterococcus faecalis (2/4), Enterococcus faecium (128/>128), Enterobacteriaceae (0.06/0.25), Pseudomonas aeruginosa (0.5/8), Acinetobacter baumannii (0.25/2), Haemophilus influenzae (0.12/0.25), and Moraxella catarrhalis (0.03/0.06). According to the regression curve, the zone diameter breakpoints were 24 and 19 mm for MICs of 1 and 4 mg/L, respectively. This study confirms the potent in vitro activity of doripenem against Pseudomonas aeruginosa, Acinetobacter, Enterobacteriaceae, MSSA, MSCoNS, and respiratory pathogens. According to the EUCAST MIC breakpoints (mg/L) ≤1/>4 for Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter, and ≤1/>1 for streptococci, pneumococci, and Haemophilus, the zone diameter breakpoints could be (mm) ≥24/<19 and ≥24/<24, respectively.

Preliminary clinical study using a multiplex real-time PCR test for the detection of bacterial and fungal DNA directly in blood.

Early diagnosis of sepsis, rapid identification of the causative pathogen(s) and prompt initiation of appropriate antibiotic treatment have a combined impact on mortality due to sepsis. In this observational study, a new DNA-based system (LightCycler SeptiFast (LC-SF) test; Roche Diagnostics) allowing detection of 16 pathogens at the species level and four groups of pathogens at the genus level has been evaluated and compared with conventional blood cultures (BCs). One hundred BC and LC-SF results were obtained for 72 patients admitted to the intensive-care unit over a 6-month period for suspected sepsis. Microbiological data were compared with other biological parameters and with clinical data. The positivity rate of BCs for bacteraemia/fungaemia was 10%, whereas the LC-SF test allowed detection of DNA in 15% of cases. The LC-SF performance, based on its clinical relevance, was as follows: sensitivity, 78%; specificity, 99%; positive predictive value, 93%; and negative predictive value, 95%. Management was changed for four of eight (50%) of the patients because organisms were detected by the LC-SF test but not by BC. LC-SF results were obtained in 7-15 h, in contrast to the 24-72 h required for BC. According to the LC-SF results, initial therapy was inadequate in eight patients, and antibiotic treatment was changed. Our results suggest that the LC-SF test may be a valuable complementary tool in the management of patients with clinically suspected sepsis.

Susceptibility of Pseudomonas aeruginosa to antimicrobials: a 2004 French multicentre hospital study.

OBJECTIVES: Pseudomonas aeruginosa is a major causative agent of hospital infections. The purpose of this study was to determine the antibiotic susceptibility of P. aeruginosa in a French multicentre study and to investigate the mechanisms of beta-lactam resistance. METHODS: Four hundred and fifty non-repetitive strains of P. aeruginosa were collected in 15 French university hospitals in 2004. MICs of antibiotics were measured by agar dilution methods. For all the strains with MICs of ticarcillin >16 mg/L, detection and identification of the beta-lactamases, quantitative determination of cephalosporinase and overproduction of the MexAB-OprM efflux pump were evaluated. RESULTS: The percentages of susceptible isolates were as follows: ticarcillin, 62%; ticarcillin + clavulanic acid, 61%; piperacillin, 78%; piperacillin + tazobactam, 80% (MICs

Pseudomonas aeruginosa: resistance and therapeutic options at the turn of the new millennium.

Pseudomonas aeruginosa is a major cause of nosocomial infections. This organism shows a remarkable capacity to resist antibiotics, either intrinsically (because of constitutive expression of beta-lactamases and efflux pumps, combined with low permeability of the outer-membrane) or following acquisition of resistance genes (e.g., genes for beta-lactamases, or enzymes inactivating aminoglycosides or modifying their target), over-expression of efflux pumps, decreased expression of porins, or mutations in quinolone targets. Worryingly, these mechanisms are often present simultaneously, thereby conferring multiresistant phenotypes. Susceptibility testing is therefore crucial in clinical practice. Empirical treatment usually involves combination therapy, selected on the basis of known local epidemiology (usually a beta-lactam plus an aminoglycoside or a fluoroquinolone). However, therapy should be simplified as soon as possible, based on susceptibility data and the patient's clinical evolution. Alternative drugs (e.g., colistin) have proven useful against multiresistant strains, but innovative therapeutic options for the future remain scarce, while attempts to develop vaccines have been unsuccessful to date. Among broad-spectrum antibiotics in development, ceftobiprole, sitafloxacin and doripenem show interesting in-vitro activity, although the first two molecules have been evaluated in clinics only against Gram-positive organisms. Doripenem has received a fast track designation from the US Food and Drug Administration for the treatment of nosocomial pneumonia. Pump inhibitors are undergoing phase I trials in cystic fibrosis patients. Therefore, selecting appropriate antibiotics and optimising their use on the basis of pharmacodynamic concepts currently remains the best way of coping with pseudomonal infections.

[Analysis of the factors influencing the internal reporting of nosocomial infections. A review of 108 notifications]. / Analyse des facteurs influençant la démarche de signalement interne d'infection nosocomiale. A propos de 108 signalements.

INTRODUCTION: Since July 26, 2001, the external reporting to the regional office of health and social affairs (Direction départementale des affaires sanitaires et sociales--Ddass) and the coordination centre (Comité de lutte contre les infections nosocomiales--Cclin) for the fight against nosocomial infections (NI) is mandatory. However, the modalities of internal reporting to the Clin are unknown. METHOD: We performed a retrospective analysis of 108 cases of NI reported over 23 months in 4 medical-surgical departments (MSD) with 14 to 35 NI reported/MSD. The distribution of the bacteria responsible was compared with that of the local epidemiological state (chi2 test). A correlation analysis was performed between the number of NI reported in each MSD and the structural characteristics and activity index of these MSD (Spearmann's correlation test). RESULTS: The NI were predominantly infections related to a catheter (43), lower respiratory tract (25) and infection of the site of surgery (19). Ninety were documented biologically, among which 10 implied multi-resistant bacteria. Ninety-four NI were associated with the prescription of an antibiotic. Compared with the local epidemiological state, the NI reported generally implied multi-resistant bacteria (p=0.009). The other microbiological data had little implication. In each of the MSD, the number of cases reported was independent of: the global activity, the number of interventions, the mean duration of hospitalisation, the number of beds, the number of clinicians, the number of new patients managed and the chemotherapy outpatient activity. Conversely, there was a strong correlation between the global consumption of antibiotics (r=0.78), and the number of the Clin members in each MSD DMC (r=0.82). CONCLUSION: In each MSD, the internal reporting of NI relies on the discovery of multi-resistant bacteria, but above all on the implication of those involved in the fight against nosocomial infections.

[Early and late nosocomial broncho-pulmonary diseases in intensive care. Comparative study of risk factors and of causing bacteria]. / Infections broncho-pulmonaires nosocomiales précoces et tardives en réanimation. Etude comparative des facteurs de risque et des germes responsables.

OBJECTIVES: Determine the risk factors and germs responsible for early-onset (E) and late-onset (L) nosocomial broncho-pulmonary infections (NBPI), in order to improve preventive strategies and the choice of initial antibiotherapy. METHODS: An observational prospective study conducted in an intensive care unit of 30 beds, from March 1993 to September 1999. The patients presenting with an ENBPI and those with an LNBPI were compared with patients without NBPI using univariate and then multivariate analysis. RESULTS: 517 (14%) of early-onset NBPI were diagnosed, but the majority of NBPI were late-onset (87%). Multiresistant bacteria predominated. The similarity in the germs responsible for the early and late onset forms of NBPI was probably related to the large number of patients transferred from other departments (82%) and having already received antibiotics before their admission to the intensive care unit (49%). Multivariate analysis identified anti-ulcer and long term corticosteroid treatments as common risk factors for early and late onset forms of NBPI, digestive failure, tracheotomy and kidney failure as risk factors for ENBPI and the number of antibiotics used in intensive care and the duration of mechanical ventilation as factors of risk for LNBPI. CONCLUSION: The limited use of antibiotics and anti-ulcer agents could improve the prevention of early and late onset forms of NBPI. The distinction in intensive care between the two forms of NBPI must be emphasized by the notion of prior hospitalization.

Clinical and microbiological epidemiology of Streptococcus pneumoniae bacteremia in eight French counties.

OBJECTIVE: To describe the incidence of pneumococcal bacteremia not associated with infection of the central nervous system, investigate the susceptibility of bacterial isolates to beta-lactams, evaluate risk factors for antibiotic resistance, and determine factors predicting patient outcome. METHODS: Over a period of 1 year, 919 Streptococcus pneumoniae isolates were collected from 919 patients with bacteremia in eight French counties. Their clinical and microbiological features were recorded. Univariate and multivariate analyses were used to determine risk factors for penicillin-non-susceptible pneumococcal bacteremia and predictors of fatal outcome. RESULTS: Of the 919 patients in the study, 27% were infected with penicillin-non-susceptible pneumococci (PNSP): 17.8% of the isolates were intermediate to penicillin, 7.2% were resistant to penicillin, 16% were intermediate to amoxicillin, and 11% were intermediate to cefotaxime; no PNSP were resistant to either of the last two antibiotics. The most common PNSP serotypes isolated were 14 (41%) and 23 (24%). A statistically significant relationship between PNSP infection and age below 5 years or above 60 years in the different counties was observed by univariate and multivariate analysis. Gender, origin of bacteremia, co-morbidity, immunodeficiency, previous hospitalization and nosocomial infection were not predisposing factors associated with PNSP. The mortality rate was 20.6%: there was no increase in mortality among patients with PNSP bacteremia. Age was the strongest risk factor for mortality, but immunodeficiency also seemed to have had an impact on mortality. Clinical outcome was more closely related to clinical conditions than to the susceptibility status of S. pneumoniae. CONCLUSION: Among cases of bacteremia, 27% were caused by PNSP, but this level varies according to the counties and the age of the patients. Infection-related mortality was high, but there was no increase related to penicillin G non-susceptibility of the infecting strain.

Surveillance of methicillin-resistant Staphylococcus aureus (MRSA) and Enterobacteriaceae producing extended-spectrum beta-lactamase (ESBLE) in Northern France: a five-year multicentre incidence study.

In order to measure the incidence of methicillin-resistant Staphylococcus aureus (MRSA) and of Enterobacteriaceae producing extended-spectrum beta-lactamase (ESBLE), and to evaluate the impact of the national guidelines for multidrug-resistant bacteria (MDRB) prevention in hospitals of Northern France, a multicentre study was conducted for three months every year starting in 1996, in volunteer hospital laboratories. All clinical specimens positive for MRSA and ESBLE were prospectively surveyed. During the five-year surveillance period, the overall proportion of MRSA was 38.4% in the 28,534 strains of S. aureus, and that of ESBLE was 11.4% in the 6121 strains of Klebsiella pneumoniae and 47.7% in the 2353 strains of Enterobacter aerogenes. The overall incidence rates of clinical specimens positive for MRSA, ESBL-K. pneumoniae and E. aerogenes were 0.84. 0.05 and 0.12/1000 hospital-days (HD), respectively. In the 23 hospitals that participated in the survey every year, the proportion and incidence of ESBLE decreased. Hence, despite recommendations as for isolation precautions, MRSA remains poorly controlled and requires more effective measures.

Susceptibility of Enterobacteriaceae to beta-lactam agents and fluoroquinolones: a 3-year survey in France.

OBJECTIVE: To assess trends in the susceptibility to beta-lactam agents and to fluoroquinolones of clinically relevant Enterobacteriaceae isolated over a 3-year period in 14 French hospital laboratories. METHODS: During the second quarter of 1996, 1997 and 1998, 180 consecutive non-duplicate isolates of Enterobacteriaceae were collected in each center. Sixteen beta-lactams and four quinolones were tested by the disk diffusion method. In addition, the double-disk synergy test was used to screen for the production of extended-spectrum beta-lactamase (ESBL). RESULTS: Totals of 2507, 2312 and 2506 clinical isolates were obtained in each period, respectively. The distribution of Enterobacteriaceae species according to clinical specimens and wards was similar in each study period. No significant variation in the susceptibility rates to beta-lactams and fluoroquinolones was observed, except in Klebsiella pneumoniae and Enterobacter aerogenes. The prevalence of ESBL-producing isolates decreased from 18% to 9% in the former, while it increased from 32% to 54% in the latter. At the same time, the susceptibility to ofloxacin and pefloxacin increased for K. pneumoniae (P < 0.003) and cephalosporinase-producing species (P < 0.05), except Enterobacter spp. CONCLUSION: Over the 3-year study period beta-lactams and fluoroquinolones remained highly active against Enterobacteriaceae clinical isolates, with the exception of E. aerogenes, probably as a result of the dissemination of multiresistant clones in French hospitals.

Change of pneumococcal resistance to antibiotics in adults between 1995 and 1997: a study in eight French counties.

The main object of this study was to describe the evolution of antibiotic resistance in pneumococci from adults, in eight French counties of France between 1995 and 1997. Despite the high and increasing prevalence (23-35%) of pneumococci with diminished susceptibility to penicillin G (PSDP), resistance to amoxycillin (0.8-0.5%) and to cefotaxime (0-0.3%) was rare in both 1995 and 1997 respectively. The percentage of pneumococci resistant to penicillin G (PRP, minimum inhibitory concentration >1 mg/l) remained stable between the two periods. PSDP showed increased resistance to macrolides (30-41%), to cotrimoxazole (28-34%) and to tetracycline (19-25%). These figures are lower than those obtained over the same periods and the same regions in children. The distribution of PSDP serotypes isolated in adults was the same as that seen in children: by descending order serotypes 23, 14, 9 and 6. This study by the Regional Pneumococcal Observatories confirms the high prevalence and the main characteristics of antibiotic resistance among pneumococci with variations in levels of resistance with the age of patients, with the site of sampling and from one Observatory to another.

Worldwide prevalence of antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the SENTRY Antimicrobial Surveillance Program, 1997-1999.

The in vitro activities of numerous antimicrobials against clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis from patients with bloodstream and respiratory tract infections in the United States, Canada, Europe, Latin America, and the Asia-Pacific region were studied in the SENTRY Antimicrobial Surveillance Program. Penicillin resistance (minimum inhibitory concentration, > or =2 microg/mL) was noted in all 5 geographic regions, and a high and increasing rate of macrolide resistance among S. pneumoniae isolates was observed. Elevated rates of resistance to clindamycin, trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline were seen. beta-Lactamase-mediated resistance in H. influenzae to amoxicillin and variable trimethoprim-sulfamethoxazole resistance by region were documented. Resistance to several drugs continues to emerge among pneumococci worldwide, but more stable resistance patterns have been noted for H. influenzae and M. catarrhalis. Continued surveillance of this pathogen group appears to be prudent.

[Pneumococcal antibiotic resistance. Data from 6 regional registries for 1999]. / Résistance du pneumocoque aux antibiotiques. Données de 6 observatoires régionaux pour l'année 1999.

RESISTANCE BY REGION: Resistance varied greatly by region, ranging from 34.2% resistant strains in Alsace to 63.1% in Brittany. The incidence of resistant strains was always higher in children (especially in children aged 1 to 5 years) and in ENT samples. The time course of resistance has varied between regions, as has that of serotypes. CRUCIAL FINDING: In these 6 regions, and despite a high incidence (that varied from one region to another) of reduced susceptibility strains for penicillin G, amoxicillin (19-32%) and cefotaxime (6.5-18.5%), amoxicillin-cefotaxime resistant strains remained very rare (0.2-3.5%).

Keratinocyte growth factor protects against Pseudomonas aeruginosa-induced lung injury.

We have previously reported that keratinocyte growth factor (KGF) attenuates alpha-naphthylthiourea-induced lung injury by upregulating alveolar fluid transport. The objective of this study was to determine the effect of KGF pretreatment in Pseudomonas aeruginosa pneumonia. A 5% bovine albumin solution with 1 microCi of (125)I-labeled human albumin was instilled into the air spaces 4 or 24 h after intratracheal instillation of P. aeruginosa, and the concentration of unlabeled and labeled proteins in the distal air spaces over 1 h was used as an index of net alveolar fluid clearance. Alveolocapillary barrier permeability was evaluated with an intravascular injection of 1 microCi of (131)I-albumin. In early pneumonia, KGF increased lung liquid clearance (LLC) compared with that in nonpretreated animals. In late pneumonia, LLC was significantly reduced in the absence of KGF but increased above the control value with KGF. KGF pretreatment increased the number of polymorphonuclear cells recovered in the bronchoalveolar lavage fluid and decreased bacterial pulmonary translocation. In conclusion, KGF restores normal alveolar epithelial fluid transport during the acute phase of P. aeruginosa pneumonia and LLC in early and late pneumonia. Host response is also improved as shown by the increase in the alveolar cellular response and the decrease in pulmonary translocation of bacteria.

Effects of dental plaque antiseptic decontamination on bacterial colonization and nosocomial infections in critically ill patients.

OBJECTIVES: To document in intensive care unit (ICU) patients the effect of dental plaque antiseptic decontamination on the occurrence of plaque colonization by aerobic nosocomial pathogens and nosocomial infections. DESIGN: Single-blind randomized comparative study. SETTING: A 16-bed adult intensive care unit in a university hospital. PATIENTS: Patients consecutively admitted in the ICU with a medical condition suggesting an ICU stay of 5 days and requiring mechanical ventilation. INTERVENTIONS: After randomization, the treated group received dental plaque decontamination with 0.2% chlorhexidine gel, three times a day during the ICU stay. The control group received standard oral care. SPECIFIC MEASUREMENTS: Dental status was assessed by the Caries-Absent-Occluded index; the amount of dental plaque was assessed by a semi-quantitative plaque index. Bacterial sampling of dental plaque, nasal and tracheal aspirate, blood, and urine cultures were done on days 0, 5, 10, and every week. MAIN RESULTS: Sixty patients were included; 30 in the treated group and 30 in the control one (mean age: 51 +/- 16 years; mean Simplified Acute Physiological Score II: 35 +/- 14 points). On admission, no significant differences were found between both groups for all clinical and dental data. Compared with the control group, the nosocomial infection rate and the incidence densities related to risk exposition were significantly lower in the treated group (18 vs 33% days in the ICU and 10.7 vs 32.3% days of mechanical ventilation; P < 0.05). These results were consistent with a significant preventive effect of the antiseptic decontamination (Odds Ratio: 0.27; 95% CI: 0.09; 0.80) with a 53% relative risk reduction. There was a trend to a reduction of mortality, length of stay, and duration of mechanical ventilation. CONCLUSIONS: An antiseptic decontamination of dental plaque with a 0.2% chlorhexidine gel decreases dental bacterial colonization, and may reduce the incidence of nosocomial infections in ICU patients submitted to mechanical ventilation.

Peritonitis due to Staphylococcus sciuri in a patient on continuous ambulatory peritoneal dialysis.

Among the coagulase-negative staphylococci, Staphylococcus sciuri has rarely been described as the aetiology of continuous ambulatory peritoneal dialysis (CAPD) peritonitis. It has been reported in 1 case of endocarditis and has been isolated from peritoneal dialysis fluid in 2 patients. The case reported here describes CAPD peritonitis due to S. sciuri shortly after a previous episode due to S. aureus, showing the necessity to identify coagulase-negative staphylococci to find new species that cause CAPD peritonitis.