Automated detection of nosocomial infections: evaluation of different strategies in an intensive care unit 2000-2006.

The aim of this study was to evaluate seven different strategies for the automated detection of nosocomial infections (NIs) in an intensive care unit (ICU) by using different hospital information systems: microbiology database, antibiotic prescriptions, medico-administrative database, and textual hospital discharge summaries. The study involved 1,499 patients admitted to an ICU of the University Hospital of Lyon (France) between 2000 and 2006. The data were extracted from the microbiology laboratory information system, the clinical information system on the ward and the medico-administrative database. Different algorithms and strategies were developed, using these data sources individually or in combination. The performances of each strategy were assessed by comparing the results with the ward data collected as a national standardised surveillance protocol, adapted from the National Nosocomial Infections Surveillance system as the gold standard. From 1,499 patients, 282 NIs were reported. The strategy with the best sensitivity for detecting these infections using an automated method was the combination of antibiotic prescription or microbiology, with a sensitivity of 99.3% [95% confidence interval (CI): 98.2-100] and a specificity of 56.8% (95% CI: 54.0-59.6). Automated methods of NI detection represent an alternative to traditional monitoring methods. Further study involving more ICUs should be performed before national recommendations can be established.

Multiplex real-time PCR and blood culture for identification of bloodstream pathogens in patients with suspected sepsis.

Severe sepsis is increasingly a cause of death. Rapid and correct initial antimicrobial treatment reduces mortality. The aetiological agent(s) cannot always be found in blood cultures (BCs). A novel multiplex PCR test (SeptiFast (alpha version)) that allows identification of 20 bacterial and fungal species directly from blood was used, comparatively with BC, in a multicentre trial of patients with suspected bacterial or fungal sepsis. Five hundred and fifty-eight paired samples from 359 patients were evaluated. The rate of positivity was 17% for BC and 26% for SeptiFast. Ninety-six microorganisms were isolated with BC, and 186 microorganisms were identified with SeptiFast; 231 microorganisms were found by combining the two tests. Of the 96 isolates identified with BC, 22 isolates were considered to be contaminants. Of the remaining 74 non-contaminant BC isolates available for comparison with SeptiFast, 50 were identified as a species identical to the species identified with SeptiFast in the paired sample. Of the remaining 24 BC isolates for which the species, identified in the BC, could not be detected in the paired SeptiFast sample, 18 BC isolates were identified as a species included in the SeptiFast master list, and six BC isolates were identified as a species not included in the SeptiFast master list. With SeptiFast, 186 microorganisms were identified, 12 of which were considered to be contaminants. Of the 174 clinically relevant microorganisms identified with SeptiFast, 50 (29%) were detected by BC. More than half of the remaining microorganisms identified with SeptiFast (but not isolated after BC) were also found in routine cultures of other relevant samples taken from the patients. Future clinical studies should assess whether the use of SeptiFast is of significant advantage in the detection of bloodstream pathogens.

[Monitoring of antibiotic resistance of gram negative anaerobes]. / Surveillance de la résistance aux antibiotiques des anaérobies stricts à Gram négatif.

MATERIAL AND METHOD: Using an agar reference method (Norma M11-A5, National Committee for Clinical and Laboratory Standards) the minimal inhibitory concentrations of nine antibiotics were determined for 376 anaerobic strains. The following strains were investigated: 254 Bacteroides fragilis group (including 143 B. fragilis), 122 other gram-negative anaerobes (Bacteroides spp., Prevotella, Fusobacterium, Porphyromonas, Suterella, Desulfomonas, Veillonella). RESULTS: In the B. fragilis group resistance rates were: coamoxyclav 2.8%, ticarcillin 27.5%, ticarcillin-clavulanic acid 1.9%, piperacillin-tazobactam 1.9%, cefoxitin 6.2%, imipenem 0.8%, clindamycin 28.3%, respectively. Based on previous studies, resistance to imipenem remained low in 2003 and was only observed for B. fragilis. Resistance to clindamycin was maintained around 25%. No metronidazole resistance was observed, but decreased susceptibility was found for B. fragilis, B. merdae and Prevotella, as in 4.3% of gram-negative anaerobes. DISCUSSION: This study confirms the high resistance rate of gram-negative anaerobes to clindamycin, the efficient activity of imipenem, beta-lactam/beta-lactamase inhibitor combinations and metronidazole. However, reduced metronidazole susceptibility seems to be increasing.

[Nasopharyngeal carriage of Streptococcus pneumoniae in healthy children, 2 to 24 months of age, in New-Caledonia]. / Etude du portage rhinopharyngé de Streptococcus pneumoniae chez les enfants sains âgés de 2 à 24 mois en Nouvelle-Calédonie.

OBJECTIVES: The aims of this study were to determine the prevalence of pneumococcal nasopharyngeal carriage in New-Caledonian children less than two years of age, to define risk factors for carriage, and to document the serotypes present in New Caledonia prior to the implementation of the conjugate pneumococcal vaccine. METHOD AND RESULTS: From August 2002 to April 2003, nasopharyngeal samples were collected on 1040 children less than two years of age during scheduled visits to dispensaries for routine immunization. Of the 1040 samples, 544 (52%) were positive for Streptococcus pneumoniae. The percentage of pneumococcal strains with reduced susceptibility to penicillin (PRSP) was 21%. Several risk factors for pneumococcal carriage were identified. These included the Province that the child lived in, the ethnic group, age, and having a sibling less than 6 years of age. Risk factors for carriage of PRSP carriage were similar but also included additional risk factors such as attendance at day care and a history of antibiotic treatment. The eight most frequent serotypes were 6B, 19F, 14, 23F, 6A, 19A, 11A, and 16F. These serotypes accounted for 60% of all strains detected. The most frequent serotypes of PRSP were 14, 9 V, 19F, 23F, and 6B. They were more often identified in european children and 80% were vaccine serotypes. However, overall 250/544 (46%) of all pneumococcal isolates were those included in the 7 serotype vaccine.

Antibiotic resistance among anaerobic Gram-negative bacilli: lessons from a French multicentric survey.

Temporal changes of antibiotic susceptibilities among anaerobes in France are followed in our laboratory since 1992. For Bacteroides strains, resistance increased from 1992 to 1998 for amoxicillin-clavulanic acid, cefotetan and clindamycin. The present study evaluates the situation in 2000 for 434 Gram-negative anaerobic clinical isolates (obtained from 9 large university hospitals) by testing amoxicillin and ticarcillin alone or combined with clavulanic acid, cefoxitin, cefotetan, imipenem, clindamycin and metronidazole (using the NCCLS-approved method for MIC determination. The main genera tested included Bacteroides (359 strains of the fragilis group), Prevotella (40 strains), Fusobacterium (23 strains) and miscellaneous species (8 strains). Resistance rates within the B. fragilis group were: amoxicillin-clavulanic acid 5.6%, ticarcillin 33%, ticarcillin-clavulanic acid 2%, cefoxitin 13%, cefotetan 44%, clindamycin 33%, imipenem 1% and metronidazole <1%, respectively. Only one strain of B. fragilis was resistant to metronidazole (MIC=64 mg/L); due to the presence of the nimA gene on the chromosome. Resistance to imipenem or metronidazole was only found among the B. fragilis species. These two former drugs excepted, B. fragilis was less resistant to antibiotics than the other species. beta-lactamase production was detected for 357/359 strains of the fragilis group, 26/40 stains of Prevotella and 3/23 strains of Fusobacterium. Dynamic changes of antibacterial resistance are occurring within the B. fragilis group: decreased resistance to amoxicillin-clavulanic acid, ticarcillin-clavulanic acid, imipenem while resistance for cefoxitin, cefotetan, clindamycin continues to increase. Regular antibiotic surveys are needed as a source of information to guide the empirical therapy of anaerobic infections.

[Rhône-Alpes observatory of Streptococcus pneumoniae in 1999: 35 cases of meningitis]. / Observatoire Rhône-Alpes du pneumocoque en 1999: 35 cas de méningites.

In 1999, in Rhône-Alpes region, in a survey of resistance to antibiotics of Streptococcus pneumoniae, 35 cases of meningitis were observed. A retrospectic questionnary was sent to each participant. MICs to Penicillin, Amoxicillin and Cefotaxime were determined with ATB-PNEUMO gallery or E-test and by disk diffusion for the other antibiotics. The results were interpreted according to the recommendations of the CA-SFM. Mean age was 38.1 years (range : 1 month -78 years) and sex-ratio 2/5. Eight patients had previously received antibiotics, 22 patients had risk factors and 23 were transferred in intensive care unit. The patients received C3G + glycopeptide in 15 of 16 children and in 13/19 adults according to the consensus recommendations. Diagnostic was made on the direct examination of CSF in 83%, and blood cultures was positive in 74.3% of cases. The percentage of PRP was 48.6% with 17.1% of intermediate-amoxicilline and 14.3% intermediate-cefotaxime strains. Resistance to trimethoprim-sulfamethoxazole was 45.7%, to chloramphenicol 30% and to fosfomycin 6.9%. All the strains were susceptible to rifampicin and vancomycin. Among the 17 PRP strains, 7 were belonging to serotype 6 (6 in children). The clinical outcome was fatal in 7 male cases (20%), without risk factors in 3 children and 6 of 7 strains were susceptible to penicillin. Six patients (17%) had auditive and/or neurologic sequellaes. This study shows that nearly 50% of strains isolated in meningitis, in Rhône-Alpes region, were not susceptible to penicillin, and confirms the frequency of sequellaes while the mortality is not related with the resistance of strains to the antibiotics.

Comparative in vitro activity of penicillin G, levofloxacin, moxifloxacin, telithromycin, pristinamycin, quinupristin-dalfopristin and linezolid against ofloxacin-intermediate and -resistant Streptococcus pneumoniae.

Screening by ofloxacin disk was carried out on 1158 strains of Streptococcus pneumoniae in order to investigate the in vitro bacteriostatic activity of penicillin G, levofloxacin, moxifloxacin, telithromycin, linezolid, pristinamycin and quinupristin-dalfopristin against ofloxacin-intermediate and -resistant S. pneumoniae strains. It was concluded that these new antimicrobial agents could be useful for the treatment of pneumococcal infections caused by penicillin-sensitive and -resistant S. pneumoniae, and would represent a valid therapeutic option for patients allergic to beta-lactams, should they prove to be potent in vivo.

[Evaluation of the E-test and the ATB-PNEUMo battery for determining the beta-lactam MIC for Streptococcus pneumoniae in daily practice]. / Evaluation du E-test et de la galerie ATB-PNEUMo dans la détermination des CMI aux bêtalactamines de Streptococcus pneumoniae en pratique quotidienne.

In 1999, during the survey of resistance of Streptococcus pneumoniae to antibiotics by 31 clinical laboratories of Rhône-Alpes area, MIC to penicillin (P), amoxicillin (AMX) and cefotaxime (CTX) of 877 PRP strains or with a diameter of inhibition to oxacillin inferior to 26 mm, were determined by each institution by E-test (n = 220 strains) or ATB-PNEUMO (n = 657 strains). MICs of these three antibiotics were determined by dilution in agar medium by the coordinating center. The essential agreement was respectively for ATB-PNEUMO and E-test 89% versus 84% for P (p > 0.05), of 86% vs 79% for AMX (p < 0.01), and of 91% vs 86% for CTX (p = 0.03). When the strains were classified in clinical category, the differences were significant (p < 0.001) for AMX (85% vs 71%) and for CTX (82% vs 75%) but not for P (73% vs 78%). ATB-PNEUMO method was more sensitive than E-test for the detection of strains susceptible to P (90 vs 73%), to AMX (83 vs 78%) and to CTX (80 vs 72%) and for the strains intermediate to AMX (90 vs 78%). On the contrary, E-test is more specific than ATB-PNEUMO for the detection of P-resistant strains (94 vs 86%). Finally, the specificity of both methods is the same for detection of P-S, AMX-R and CTX-I strains.

[Pneumococcal antibiotic resistance in 1999. Results from 19 registries for 1999]. / Résistance du pneumocoque aux antibiotiques. Résultats portant sur 19 observatoires pour l'année 1999.

BETA-LACTAM RESISTANCE: Among the 9956 strains of Streptococcus pneumoniae isolated in adults, 39% had some degree of penicillin resistance (reduced susceptibility), but there were relatively few strains highly resistant to penicillin: 10%. Among the 4422 strains isolated in children, the overall rate of penicillin resistance was higher (51%) with 15% highly resistant strains. For amoxicillin, the rate of reduced susceptibility was 25% while 1.4% were amoxicillin-resistant. For ceftaxime the respective figures were 21% and 0.3% OTHER ANTIBIOTIC FAMILIES: Important reduction in the susceptibility of all strains, more pronounced for peni-R strains, for macrolides, cotrimoxazole, tetracyxine and chloramphenicol. Very rare resistance to rifampicin and intact susceptibility to vancomycin. CHILDREN VERSUS ADULTS: The rate of reduced susceptibility to beta-lactams was higher in children: 31% versus 23% for amoxicillin and 21% versus 14% for cefotaxime. However there were only a few rare strains that were amoxicillin and cefotaxime resistant. Unlike what was observed in adults, there were major differences by site of sampling; strains isolated from purulent middle ear fluid exhibited the strongest resistance.

Resistance of bacteria in urinary tract infections.

Bacterial infection of the urinary tract is a common health problem in young women but also the most common nosocomial infection (>33%) contributing to the mortality of patients, and increasing the duration and cost of hospitalization. Escherichia coli is the most predominant organism and its prevalence varies in different studies. The high consumption of inappropriately prescribed antibiotics, combined with multiple pathology and frequent use of invasive devices, is a major factor contributing to high levels of resistance. There is a serious decrease in susceptibility of E. coli strains to amoxycillin, due to the presence of R-TEM enzymes, to cotrimoxazole and trimethoprim. Nitrofurantoin and fosfomycin-trometamol remain highly active against urinary Enterobacteriaceae, with over 90% of E. coli being susceptible. Knowledge of the most likely causative organisms and the prevalence of resistance pathogens to antimicrobial agents is essential to select antibiotics and to establish guidelines for the empirical treatment of urinary tract infections.

[Peritonitis with Mycobacterium avium complex in a patient with alcoholic cirrhosis]. / Infection du liquide d'ascite à Mycobacterium avium complex chez un malade ayant une cirrhose alcoolique.

Before highly active antiretroviral therapy were available, disseminated Mycobacterium avium complex infection was common in adults with HIV. Diagnosis was often made by blood culture in these immunocompromised patients. Although Mycobacterium avium complex disease can involve any organ of the body, infection of serosal surfaces is very rare. Mycobacterium avium complex peritonitis is rare and usually occurs in immunocompetent patients with chronic ambulatory peritoneal dialysis. We report a case of Mycobacterium avium complex peritonitis in a patient with alcoholic cirrhosis with no evidence of HIV infection. Diagnosis was made by culture of a lymphocytic ascites which showed Mycobacterium avium complex at 4 weeks. Interestingly, blood and hepatic cultures remained negative. At three months, marked improvement occurred with antimycobacterial treatment, so that orthotopic liver transplantation could be performed.

[Can one use probabilistic protocols for antibiotic therapy in intensive care units?]. / Peut-on utiliser des protocoles d'antibiothérapie probabiliste en réanimation?

Due to a large spectrum, empiric antibiotics treatments participate to the increase in bacterial resistance. In order to improve its indications, the implementation of therapeutic guidelines in an ICU was studied. Empiric therapy was administered in 30% of the 178 patients receiving antimicrobial agents. Large spectrum drugs were prescribed in 26% of empiric treatments. The mean duration of empiric antibiotics administration was 3.2 days. It was concluded that it was possible to use guidelines of empiric antibiotic in an intensive care unit.

Infections following peripheral blood progenitor cell transplantation for lymphoproliferative malignancies: etiology and potential risk factors.

PURPOSE: We sought to describe the infections that occur after large-dose chemotherapy, which was followed by autologous peripheral blood progenitor cell transplantation, and to determine their risk factors. PATIENTS AND METHODS: We retrospectively analyzed the occurrence and the characteristics of infections in 277 consecutive patients who received intensive chemotherapy for non-Hodgkin's lymphoma (n = 207), Hodgkin's disease (n = 27), or multiple myeloma (n = 43) in a single institution. Conditioning regimens included total body irradiation in 47% of the cases. Infections occurring within the 30 days after transplant were defined as early infections, whereas infections after that time in patients who had achieved a neutrophil count greater than 1.0 x 10(9)/L (1,000 per microL) were considered as late infections. RESULTS: Within the first 30 days, 172 patients had unexplained fever (62%); infections were documented in 83 patients (30%), most commonly bacteremia (57 patients). Late infections occurred in 64 (26%) of 244 evaluable patients and consisted mainly of varicella zoster virus infections (n = 36) and pneumonia (n = 16). Administration of total body irradiation [odds ratio (OR) = 2.50; 95% confidence interval (CI) 1.4 to 4.5; P = 0.002) and previous use of fludarabine (OR 2.5; CI 1.2 to 5.2; P = 0.02) and a diagnosis of myeloma (OR 2.6; CI 1.2 to 5.6; P = 0.04) were significantly associated with late infections. CONCLUSIONS: This study confirms that infectious toxicity after peripheral blood progenitor cell transplantation is usually moderate, although bacteremia remains a serious problem. Late infections are encountered in about 25% of patients and are more common in those with myeloma, or those who received total body irradiation or fludarabine.

[Pneumococcus observatory data in the Rhône-Alps region. Results from 1996]. / Observatoire du pneumocoque en région Rhône-Alpes. Résultats de l'année 1996.

Throughout 1996, 22 hospital-based laboratories in the Rhône-Alpes region of France collected pneumococcal strains and used a standardized protocol to record the following data; patient age and sex; type of specimen; and determination of susceptibility to at least the following antibiotics: oxacillin 1 microgram and 5 micrograms, erythromycin (Ery), tetracycline (Tet), chloramphenicol (Chl), rifampin (Rmp), and loracarbef. For penicillin-nonsusceptible strains (PNSSs), which were identified based on results with oxacillin, MICs for penicillin G, amoxicillin (Amx), and cefotaxime (Ctx) were determined using the E Test, at the study site and agar dilution at the coordinating center. Of the 1153 strains, 65.5% were from adults and 31.8% from children; patient age was unknown in 2.7% of cases. PNSPs (MIC > 0.06 mg/l) contributed 32.9% of strains (I: 23.3%; R: 9.6%) and were more common in children (41.1%) than in adults (28.1%). The frequency of PNSSs varied across specimen types: 27.9% in blood cultures (305 strains), 15.6% in cerebrospinal fluid (32), 38.7% in protected bronchopulmonary specimens (31), 31.5% in unprotected bronchopulmonary specimens (434), 50.8% in acute otitis media (118), and 34.4% in other specimens (221). Among PNSSs, nonsusceptibility (I + R) to other antibiotics was variable: Ery, 62.1%; Tet, 41.5%; Chl, 40.4%; Rmp, 1.1%. Corresponding figures for the overall strain population were Ery, 33.3%; Tet, 22.7%; Chl, 22.8%; Rmp, 0.9%. In addition, 56.5% of PNSSs exhibited multiple drug resistance. Resistance to amoxicillin (MIC > 2 mg/l) was demonstrated for only 5 strains. No strains were resistant to loracarbef or cefotaxime. Serotypes of the 379 PNSSs were as follows: 23F, 26.6%; 14 (25.6%); 9V (18.2%), 6 (8.7%), 15 (5%), 19 (4.5%).

[Comparison of the results of the Etest and the method for determining minimum inhibitory concentrations in solid media for penicillin G, amoxicillin, and cefotaxime for S. pneumoniae. A multicenter study]. / Comparaison des résultats du Etest et de la méthode de détermination des concentrations minimales inhibitrices en milieu solide pour la pénicilline G, l'amoxicilline et le céfotaxime chez S. pneumoniae. Une étude multicentrique.

In 1996-1997 a multicentre study was carried out on 450 Streptococcus pneumoniae strains to compare the MICs and susceptibility categories obtained with the Etest (AB Biodisk) used under routine conditions in 22 hospital laboratories in the Rhône-Alpes region, France, with those obtained by the reference technique of agar dilution performed in a single coordinating centre. Each laboratory detected penicillin resistant pneumococci (PRP) by the oxacillin disk method (1 microgram and 5 micrograms) and determined the MICs of penicillin G (PG), amoxycillin (AMX) and cefotaxime (CTX) by the Etest. All the PRP strains were collected in the coordinating centre where MICs were carried out. The strains were classified as susceptible (S), intermediate (I) and resistant (R) according to the CASFM criteria (Comité de l'Antibiogramme de la Société Française de Microbiologie). The concordance results based on susceptibility categories are as follows: PG = 67.6%, AMX = 63.6%, CTX = 71.5%. Minor errors are as follows: PG = 31.2%, AMX = 36%, CTX = 28.5%. Major and very major errors are rare (0% to 0.6%). Agreement within 1 log2 dilution was obtained for about 80% of the strains. The minor errors results from strains clustering near the breakpoints 1 mg/l (PG) and 0.5 mg/l (AMX, CTX), and from practical difficulties in routine use of the Etest. These discrepancies may result in severe therapeutic problems. This study confirms the limits of the Etest. The authors insist on standardization and rigorous use of the Etest under routine conditions.

Tonsillar diffusion kinetics of amoxycillin after oral administration of 1 g to adults.

Although amoxycillin is widely used to treat pharyngo-tonsillitis, the kinetics of tonsillar diffusion have rarely been studied. The aim of this work was to study the kinetics of amoxycillin diffusion in the tonsils of adults, by measuring tonsillar concentrations 1.5, 3, 6 and 12 h after oral administration of 1 g of amoxycillin (Clamoxyl dispersible tablet, 1 g) relative to concomitant serum levels by using an HPLC method and a microbiological technique. At enrollment, the 20 patients were randomly divided into four groups of five, corresponding to the time intervals (1.5, 3, 6 or 12 h) between the third amoxycillin intake and the start of surgery. The results given by the two assay methods correlated well (r = 0.92-0.99). Amoxycillin showed excellent penetration into the tonsils, with both tonsillar and serum concentrations exceeding the MIC for most pathogens encountered in this setting (including Streptococcus pyogenes), even 12 h after repeated dosing with 1 g of amoxycillin.

Reappraisal of the effect of temperature on the growth kinetics of Aeromonas salmonicida.

The effect of temperature (1-34 degrees C) on the maximum specific growth rate of Aeromonas salmonicida could not be described by the classical growth models; for some strains, two optimal temperatures at 23 degrees C and 30 degrees C were observed, as well as an unexpected increase in the pseudolag time above 27 degrees C. This could be explained by the presence of two subsets, notably S-layer+ and S-layer- sub-populations. The A- cells had higher growth parameters (Topt and mu opt) than the A+ cells and were selected by subcultures above 30 degrees C. Yet the relative proportion of A+ cells did not explain all the variation of mu max versus temperature, and the growth kinetics of an Aer. salmonicida isolate remained unpredictable.