Ruling out false-positive urinary Legionella pneumophila serogroup 1 and Streptococcus pneumoniae antigen test results by heating urine.

We report here false-positive urinary Legionella pneumophila serogroup 1 and Streptococcus pneumoniae antigen test results due to rabbit antilymphocyte serum treatment and provide a simple and fast solution to rule them out by heating urine.

Emergence of echinocandin-resistant Candida spp. in a hospital setting: a consequence of 10 years of increasing use of antifungal therapy?

Since their introduction in the 2000s, echinocandin drugs have become widely used for the treatment and prophylaxis of invasive fungal infections and, notably, invasive candidiasis. Although cases of breakthrough candidiasis in patients receiving echinocandins have been reported, clinical failure during echinocandin treatment due to the acquisition of resistance by a normally susceptible Candida spp. isolate is considered rare. To date, no publications have been published correlating the use of echinocandins and the emergence of echinocandin resistance among Candida species. So, our goal is to report an initial analysis of echinocandin use in relation to the emergence of resistant Candida isolates. We report here a single-centre experience of the emergence of eight resistant isolates belonging to normally susceptible Candida species in six patients receiving echinocandins. We describe the context and analyse the use of echinocandins over the previous decade. For seven of these isolates, we identified FKS gene mutations involved in decreased susceptibility. Seven isolates were obtained in 2011, on the heels of a ten-fold increase in caspofungin use over the preceding decade. In contrast, in 2012, the use of echinocandins decreased in our institution by 19.5 % and, in that year, only one Candida-resistant isolate was detected, despite the stable global epidemiology of invasive candidaemia. This work underlines the necessity of improving the prescription of antifungal drugs. Improvement in the monitoring of strain susceptibility should also be considered in order to better detect the emergence of resistant or non-susceptible yeast strains.

Trends in quinolone susceptibility of Enterobacteriaceae among inpatients of a large university hospital: 1992-98.

OBJECTIVES: To assess trends in quinolone susceptibility of Enterobacteriaceae isolated in a large university hospital. METHODS: Between 1992 and 1998, bacterial isolates were collected each year during a 3-month period to evaluate annual changes in susceptibility. In addition, the activities of fluoroquinolones (pefloxacin, norfloxacin, ofloxacin, ciprofloxacin) against nalidixic acid-resistant strains were determined by disk diffusion and MIC methodologies during the first and last year of the study. RESULTS: The susceptibility of Enterobacteriaceae to nalidixic acid was unchanged between 1992 and 1998 (86% versus 85%). However, at the species level, the susceptibility rates to nalidixic acid decreased for Escherichia coli from 92% to 89%, and for Enterobacter cloacae from 87% to 82%. In contrast, there was a 10% increase in the nalidixic acid susceptibility rates for Klebsiella pneumoniae (74% versus 83%), which was thought to be due to the control of the spread of epidemic extended-spectrum beta-lactamase (ESBL)-producing strains. The overall susceptibility of the Enterobacteriaceae to the fluoroquinolones remained high during the study period, greater than 90% in the case of ciprofloxacin. However, nalidixic acid-resistant Escherichia coli showed decreased susceptibility to ciprofloxacin between 1992 and 1998, as reflected by a decrease in median zone diameter (26 mm to 19 mm), an increase in MIC(50) (0.25 mg/L to 1 mg/L) and a shift in MIC distribution (unimodal in 1992 to bimodal in 1998). This has resulted in the reduced susceptibility of Escherichia coli to fluoroquinolones between 1992 and 1998 (pefloxacin, 95-90%; ciprofloxacin, 99-95%). CONCLUSIONS: The susceptibility of Escherichia coli to quinolones has decreased, and the level of susceptibility of the resistant strains has increased over the 7-year study period.

Residual glutaraldehyde levels in fiberoptic endoscopes: measurement and implications for patient toxicity.

Most gastroenterology societies recommend glutaraldehyde for fiberoptic endoscope disinfection. However, glutaraldehyde toxicity has been suspected in patients examined with endoscopes disinfected with this compound. The aim of our study was to determine the residual levels of glutaraldehyde in fiberoptic endoscopes after either manual or automatic disinfection and to evaluate the extent of toxicity. Furthermore, the procedures for disinfection currently performed by the department were compared with the new French guidelines. We used both manual and automatic disinfection procedures and flushed sterile distilled water through the lumens of endoscopes before use. Residual glutaraldehyde levels were determined using liquid chromatography coupled to spectrophotometric detection. In a total of 92 measurements it was found that residual glutaraldehyde levels were higher and more variable after manual disinfection (< 0.2-159.5 mg/L) than after automatic disinfection (< 0.2-6.3 mg/L). We conclude that local procedures for disinfection need to be improved to conform to the new French guidelines. Since thresholds for the toxic dose of glutaraldehyde and international norms for levels of residual glutaraldehyde in equipment have not been defined, additional studies combining accurate measurements in fiberoptic endoscopes and clinical observations of endoscopy patients will be required to draw more definitive conclusions.

[Endovascular treatment of aorto-iliac aneurysms. Made-to-measure endoprotheses increase the feasibility]. / Traitement endovasculaire des anévrismes aorto-iliaques. La confection astisanale sur mesure des endoprothèses augmente le taux de faisabilité.

The authors describe their experience of tailoring endoprostheses for endovascular treatment of aorto-iliac aneurysms with components available on the market. Between January 1996 and December 1999, 188 aorto-iliac aneurysms were treated by tailor-made endoprostheses using self-expanding Z stents made of stainless steel compiled with polyester ligatures and covered with standard commercially available polyester prostheses. These endoprostheses were implanted with an 18 to 24 Fr (usually 20 Fr) introducer and positioned by a surgical approach. This method allows construction of tubular, bifurcated, digressive or occlusive endoprostheses associated with an extra-anatomical bypass graft. It increased the number of endovascular procedures for aorto-iliac aneurysms in the authors' department. This number has been further increased by using endoprostheses with an uncovered proximal or distal stent for cases with particularly short or angled necks and by using hybrid endoprostheses with one or more extremities without a stent, allowing surgical suture of the anastomosis. The authors' results show that tailoring endoprostheses considerably increased the feasibility of endovascular treatment of aorto-iliac aneurysms, even in unselected patients whilst providing an effectiveness and safety to justify the continuation of this experience.

[Evolution of the resistance of Streptococcus pneumoniae to erythromycin at the Pitié-Salpêtrière Hospital (1980-1984)]. / Evolution de la résistance de Streptococcus pneumoniae à l'érythromycine à l'Hôpital de la Pitié-Salpêtrière (1980-1984).

From January 1980 to December 1984, 563 swabs for Streptococcus pneumoniae were isolated at the Pitié-Salpêtrière hospital in Paris, and of these 63 were resistant to erythromycin. The percentage of swabs resistant to erythromycin rose from 2.7% in 1980 to 19.6% in 1984 and was similar for cultures of blood, serous fluid, bronchial secretions, otolaryngological specimens and smears from the conjunction. For swabs resistant to erythromycin these belonged almost exclusively (57 out of 60 or 90%) to the serotypes 6, 14, 19 and 23; one may ask whether the rise in resistance of S. pneumoniae to erythromycin was due to a rise in the frequency of isolation of these serotypes? Between 1980 and 1984 such rise took place since the frequency of isolation of S. pneumoniae belonging to the serotypes 6, 14, 19 or 23 rose from 38% in 1980 to 50% in 1984, but the rise was not significant (p = 0.1). In fact S. pneumoniae serotypes 6, 14, 19 or 23 have become resistant is significant (p less than 0.05). Two factors should be taken into consideration when interpreting these facts. The first is the increased consumption of macrolide antibiotics which doubled overall between 1979 and 1983, both at the Pitié-Salpêtrière hospital and in the Public Assistance hospitals of Paris as well as provincial hospitals throughout France. The second factor is the strictly hospital nature of this study which may have led to an overestimation of the frequency of resistance of S. pneumoniae to erythromycin.

Fast specific separation and sensitive quantification of bactericidal and sporicidal aldehydes by high-performance liquid chromatography: example of glutaraldehyde determination.

This article describes the design and the validation of the HPLC determination of glutaraldehyde at g/l and mg/l concentrations, after derivatization by 2,4-dinitrophenylhydrazine and using the external standard method. At low concentrations, the reaction mixture needs to be heated and a weight ratio of 500 for the 2,4-dinitrophenylhydrazine reagent and the glutaraldehyde ensures a linear calibration curve. In contrast, high concentrations do not require heating of the reaction mixture and a weight ratio of 32 proved to be sufficient. The optimized HPLC method has been validated for both ranges of concentrations. Between 1.25 and 10 mg/l, the content can be determined by the external standard method, with a repeatability of 0.5%. The detection limit is 0.2 mg/l. Between 0.31 and 2.5 g/l, the content can also be determined by the external standard method, with a repeatability of 0.4%. Finally, statistical analysis has demonstrated that aqueous solutions of glutaraldehyde are stable for at least three days at 4 degrees C within the mg to g range.

[Resistance of Enterobacteria to cefotaxime and lamoxactam at the Pitié-Salpêtrière Hospital in 1982]. / Situation de la résistance des Entérobactéries au céfotaxime et au lamoxactam au groupe hospitalier Pitié-Salpêtrière en 1982.

Systematic collection of data on every Enterobacteriaceae clinical isolate cultured in the Central Bacteriology Laboratory allowed comparison of the percentage of cefotaxim (CTX) and moxalactam ( MOX ) intermediate or resistant (IR) strains among the 8 199 Enterobacteriaceae isolated in 1982 and the 5 032 Enterobacteriaceae isolated in 1980. In 1982, IR rates were 2% to CTX and 0.6% to MOX . Among the 166 strains IR to CTX, 28% were also IR to MOX . Two strains only were IR to MOX but not to CTX. No E. coli, P. mirabilis or Klebsiella strains IR to CTX or MOX were isolated. On the opposite, percentages of strains IR to CTX or MOX were respectively 2.5 and 0 for indole positive Proteus, 6 and 3.6 for Enterobacter, 7.4 and 0.5 for Serratia and 17.2 and 2.5 for Citrobacter. Strains IR to CTX or MOX represented 3.3%, 2.5% and 1% of Enterobacteriaceae isolated from pus, urine and blood cultures, and 4.7%, 2.2% and 1.3% of those isolated in urology, surgery and medicine. Between 1980 and 1982, there was a simultaneous increase in the consumption of CTX and MOX (10 fold) and in the percentage of Enterobacteriaceae IR to CTX (2 fold); this last involved Serratia (9 fold) more than Citrobacter (3 fold) and spared Enterobacter.

Characterization of gentamicin-susceptible strains of methicillin-resistant Staphylococcus aureus involved in nosocomial spread.

We report an outbreak of epidemic Staphylococcus aureus strains characterized by an unusual heterogeneous resistance to methicillin and resistance to tobramycin but susceptibility to gentamicin (gentamicin-susceptible methicillin-resistant S. aureus [GS-MRSA]), contrasting with gentamicin-resistant homogeneous MRSA (GR-MRSA) that have been endemic in our hospital since the 1970s. A total of 97 GS-MRSA strains, which were shown by DNA hybridization to carry the mecA and ant(4')-Ia genes, were studied. The 40 GS-MRSA strains isolated at the beginning of the outbreak (January 1992 to June 1993) were typed by using resistance patterns, phage typing, serotyping, and pulsed-field gel electrophoresis and were compared with GR-MRSA and methicillin-susceptible S. aureus (MSSA) strains isolated during the same period. Two dominant clones, A::1 and B::3, and one minor clone, C::5, were identified among the 40 GS-MRSA strains, according to pulsotypes (A to C) and their resistance patterns (1, 3, and 5), which were distinguishable from those of GR-MRSA and MSSA strains. A selection of 57 GS-MRSA strains, isolated from 1994 to 1996, were clustered in the same three clones. However, their distribution had changed in comparison with that in the 1992 to 1993 period: clone A::1 remained dominant (47 versus 42.5%), whereas clone B::3 progressively declined (5 versus 35%) and clone C::5, the most susceptible to antibiotics, spread (44 versus 2.5%). Epidemiological investigations revealed that some clones had been introduced via patients transferred from other hospitals and that cross-infection occurred within and between wards. Major changes in the use of antibiotics, especially aminoglycosides, cyclines, and macrolides, likely played a role in the emergence and spread of GS-MRSA strains.

[Evolution of susceptibility of aerobic gram-negative aerobic bacilli to quinolones and fluoroquinolones in a university hospital (1992-2000)]. / Evolution de la sensibilité aux quinolones et aux fluoroquinolones des bacilles à Gram négatif aérobies isolés dans un hôpital universitaire (1992-2000).

Susceptibility to quinolones of aerobic gram-negative bacilli was assessed in a 2000-bed university hospital from 1992 to 2000. There was a significant downward trend in the rate of susceptibility to nalidixic acid (Nal) for Enterobacteriaceae as a whole from 1992 to 2000 (86% vs 82%), and E. coli (92% vs 84%), and an upward trend for K. pneumoniae (74% vs 82%), the latter being related to the control of the spread of epidemic ESBL producing strains. The overall susceptibility of Enterobacteriaceae to ciprofloxacin (Cip) paralleled the susceptibility to Nal: decreased susceptibility for Enterobacteriaceae as a whole (96% vs 89%) and E. coli (99% vs 91%). A clear decrease in the level of susceptibility to Cip occurred during the study period among the Nal-resistant strains as demonstrated by the decrease in the median zone diameter (D) observed among the Nal-resistant strains of E. coli (26 mm in 1992 vs 19 mm in 1998-2000). The zone diameter distribution pattern changed from an unimodal distribution in 1992 to a trimodal distribution in 2000 secondary to the occurrence of a population of resistant strains (D = 13 mm) and of a highly resistant population (D = 6 mm). Finally, the susceptibility to Cip of P. aeruginosa strains remained stable around 62% throughout the study period.

A randomized comparison of two clarithromycin doses for treatment of Mycobacterium avium complex infections.

Two dosages of clarithromycin were compared for treatment of disseminated Mycobacterium avium disease of AIDS patients: high-dose (HD): 1,000 mg or 750 mg b.i.d. according to body weight, and low-dose (LD): 1,000 mg or 750 mg q.d. Patients with high probability of M. avium positive blood culture on day 0 received a 42-day clarithromycin treatment with HD (n = 27) or LD (n = 28) at random after stratification according to body weight. Assessment procedures, including quantitative blood cultures, were performed at days 14, 28 and 42. Forty-five patients were eligible for clinical and 28 for bacteriological evaluation. Bacteriological success was observed in 12 HD and 11 LD patients, partial success in one HD and two LD and failure in none of the HD and two LD (p = 0.33). Between days 0 and 42, log decreases in CFU counts/ml were (mean +/- SD) 3.13 +/- 0.82 (HD) and 2.67 +/- 1.8 (LD) (p = 0.38). Fever and night sweats significantly improved similarly in both groups; no change in spleen and liver size was observed on CT scans. Eight patients died during the study but no death was reported as drug related. Sixteen patients (HD = 6, LD = 10) discontinued the treatment because of side effects. A trend towards improved bacteriological effectiveness and reduced tolerance was observed in the HD group but the difference was not significant. With a power of 0.70, no dose effect was demonstrated between the two tested dosages. A daily dose of 1,000 mg clarithromycin was tested in drug combinations to treat disseminated M. avium infection in AIDS patients.

Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study.

BACKGROUND: Lamivudine-resistant hepatitis B virus (HBV) is found in about 15-32% of infected patients with or without co-infection with HIV-1 after 1 year of lamivudine therapy. Adefovir dipivoxil is active in vivo and in vitro against wild-type and lamivudine-resistant HBV. We assessed the safety and efficacy of a once daily dose of adefovir dipivoxil in an open-label trial for the treatment of lamivudine-resistant HBV infection in HIV-1-infected patients. METHODS: 35 HIV-1/HBV co-infected patients receiving lamivudine therapy (150 mg twice daily) as part of their current HIV-1 antiretroviral regimen were enrolled. Patients received a 10 mg once-daily dose of adefovir dipivoxil for48 weeks while maintaining their existing anti-HIV-1 therapy, including lamivudine. Patients were assessed every 4 weeks for safety and efficacy. FINDINGS: Four patients withdrew from the study (two because of adverse events), leaving 31 patients who received adefovir dipivoxil for a median of 48 weeks (range 44-48). Mean decreases in serum HBV DNA concentrations from baseline (log 8.64 copies/mL [SE log 0.08]) were 2log 3.40 copies/mL [log 0.12] at week 24 (n=31) and 2log 4.01 copies/mL [log 0.17] at week 48 (n=29; p<0.0001). Two patients underwent hepatitis B e antigen seroconversion-one at week 32 and one at week 36. Adefovir dipivoxil was generally well tolerated, but was associated with a transient increase in serum alanine aminotransferase concentrations in 15 patients. We found no significant changes in either HIV-1 RNA or CD4 cell count. INTERPRETATION: These results indicate that 48 weeks of 10 mg daily adefovir dipivoxil is well tolerated and active against lamivudine-resistant HBV in HIV-1/HBV co-infected patients.