Burden of meticillin-resistant Staphylococcus aureus infections at a Swiss University hospital: excess length of stay and costs.

BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) infections increase hospital costs primarily by prolonging patient length of stay (LOS). AIM: To estimate the health-economic burden of MRSA infections at a Swiss University hospital using different analytical approaches. METHODS: Excess LOS was estimated by: (i) multistate modelling comparing MRSA-infected and MRSA-free patients with MRSA infection as time-dependent exposure; (ii) matching MRSA-infected patients with a cohort of MRSA-uninfected patients. The economic impact was assessed by: (i) comparing cost estimates between MRSA-infected and MRSA-free patients and multiplying excess LOS by bed-day cost; (ii) comparing real costs between MRSA-infected and MRSA-colonized non-infected patients. FINDINGS: The crude mean LOS was 37.3, 33.0 and 8.8 days for MRSA-infected, MRSA-colonized and MRSA-free patients, respectively. Excess LOS attributable to MRSA infection was 11.5 [95% confidence interval (CI): 7.9-15] or 15.3 days according to multistate modelling and matched analysis, respectively. The likelihood of discharge after MRSA infection was significantly reduced (adjusted hazard ratio: 0.69; 95% CI: 0.59-0.81). Average bed-day costs for MRSA-infected patients were 1.49- and 1.26-fold higher than for the general population hospitalized in acute wards and MRSA-colonized patients, respectively. MRSA infection resulted in an average additional cost of about 800 Swiss francs per day. CONCLUSIONS: This analysis emphasizes the financial impact of MRSA infections, demonstrates the importance of accounting for time-dependent bias and confirms that multistate modelling is a valid strategy for estimating excess LOS and costs after MRSA infection.

Secular trends in nosocomial bloodstream infections: antibiotic-resistant bacteria increase the total burden of infection.

BACKGROUND: It is unknown whether rising incidence rates of nosocomial bloodstream infections (BSIs) caused by antibiotic-resistant bacteria (ARB) replace antibiotic-susceptible bacteria (ASB), leaving the total BSI rate unaffected. METHODS: We investigated temporal trends in annual incidence densities (events per 100 000 patient-days) of nosocomial BSIs caused by methicillin-resistant Staphylococcus aureus (MRSA), ARB other than MRSA, and ASB in 7 ARB-endemic and 7 ARB-nonendemic hospitals between 1998 and 2007. RESULTS: 33 130 nosocomial BSIs (14% caused by ARB) yielded 36 679 microorganisms. From 1998 to 2007, the MRSA incidence density increased from 0.2 to 0.7 (annual increase, 22%) in ARB-nonendemic hospitals, and from 3.1 to 11.7 (annual increase, 10%) in ARB-endemic hospitals (P = .2), increasing the incidence density difference between ARB-endemic and ARB-nonendemic hospitals from 2.9 to 11.0. The non-MRSA ARB incidence density increased from 2.8 to 4.1 (annual increase, 5%) in ARB-nonendemic hospitals, and from 1.5 to 17.4 (annual increase, 22%) in ARB-endemic hospitals (P < .001), changing the incidence density difference from -1.3 to 13.3. Trends in ASB incidence densities were similar in both groups (P = .7). With annual increases of 3.8% and 5.4% of all nosocomial BSIs in ARB-nonendemic and ARB-endemic hospitals, respectively (P < .001), the overall incidence density difference of 3.8 increased to 24.4. CONCLUSIONS: Increased nosocomial BSI rates due to ARB occur in addition to infections caused by ASB, increasing the total burden of disease. Hospitals with high ARB infection rates in 2005 had an excess burden of BSI of 20.6 per 100 000 patient-days in a 10-year period, mainly caused by infections with ARB.

Spondylodiscitis due to Propionibacterium acnes: report of twenty-nine cases and a review of the literature.

Propionibacterium acnes is the most frequent anaerobic pathogen found in spondylodiscitis. A documented case required microbiological proof of P. acnes with clinical and radiological confirmation of inflammation in a localized region of the spine. Microbiological samplings were obtained by surgery or aspiration under radiological control. Twelve males and 17 females (median age, 42 years) with spondylodiscitis due to P. acnes were diagnosed within the last 15 years. Three patients were immunosuppressed. All patients reported back pain as the main symptom, and most were afebrile. Three patients had a peripheral neurological deficit, one a motor deficit, and two a sensory deficit attributable to the infection; and six patients had an epidural abscess. The most frequent risk factor was surgery, which was present in the history 28 of 29 (97%) patients. The mean delay between spinal surgery and onset of disease was 34 months, with a wide range of 0-156 months. Osteosynthesis material was present in twenty-two cases (76%). In 24 (83%) patients, additional surgery, such as débridement or spondylodesis, was performed. Previous osteosynthesis material was removed in 17 of the 22 (77%) patients where it was present. Total cure was reported in all patients, except one, after a mean duration of antibiotic therapy of 10.5 weeks (range, 2-28 weeks). In conclusion, spondylodiscitis due to P. acnes is an acute infection closely related to previous surgery. The most prominent clinical feature is pain, whereas fever is rare, and the prognosis is very good.

Detection of Pneumocystis jirovecii by two staining methods and two quantitative PCR assays.

BACKGROUND: Pneumocystis jirovecii is an opportunistic pathogen that causes pneumonia, particularly in immunodeficient hosts. MATERIALS AND METHODS: We retrospectively compared the results obtained by two staining methods (toluidine blue and calcofluor white) and two quantitative (q) real time PCR assays for the detection of P. jirovecii in bronchoalveolar lavage (BAL) specimens. For the qPCR assays, we used newly selected probes and primers targeting the Kex-1 gene, which codes for a serine endoprotease, and compared the results to those from the published assay targeting the beta-tubulin gene. RESULTS: A total of 1,843 BAL specimens were analyzed microscopically in parallel, and 74 (4.0%) were found to be positive with both stains, 23 (1.2%) were positive only with the toluidine blue stain, and six (0.3%) only with the calcofluor stain (p = 0.003). Of these, a selection of 186 consecutive BAL fluid samples were tested by qPCR using the respective different primer pairs. 21 of the 186 samples (11.3%) were microscopically positive with both stains as well as qPCR positive after 18-31 cycles (corresponding to 5.24 x 10(6) copies/ml to 640 copies/ml of native BAL) using the Kex-1 primer pair and between 21-33 cycles using the beta-tubulin assay. A good correlation between semi-quantitative microscopy and the number of PCR cycles needed for a positive signal was noted. Of the remaining 165 samples, 153 (82%) were both microscopically and PCR negative (PCR with the two sets of primers); the remaining 12 samples (7%) were Kex-1-based PCR positive (from cycles 33 to 41, corresponding to 160 copies/ml of BAL or less) but microscopically negative. Of these latter samples, ten (6%) were also positive (from cycles 34 to 38) with the primers targeting the beta-tubulin gene. Taking microscopy as a reference, the sensitivity of qPCR targeting the Kex-1 gene was 100%, and the specificity was 92.4%. CONCLUSION: The sensitive qPCR analysis proved to be a rapid and reliable method to detect P. jirovecii in BAL.

Relation of Enterococcus faecalis and Enterococcus faecium isolates from foods and clinical specimens.

Clinical Enterococcus faecalis (n=65) and Enterococcus faecium (n=12) blood isolates from three Swiss hospitals were characterized with testing for resistance to antimicrobial agents, pulsed-field gel electrophoresis (PFGE), and the occurrence of virulence factors. Phenotypic determination of resistance to antimicrobial agents resulted in 20% of E. faecalis isolates showing a triple resistance against chloramphenicol, tetracycline, erythromycin, and seven isolates (two E. faecalis and five E. faecium) exhibiting a multiresistance against five or more antimicrobials. One isolate each of E. faecalis and E. faecium showed vancomycin resistance. All isolates contained at least two of the nine tested virulence genes (agg, gelE, cyl, esp, efaAfs, efaAfm, cpd, cob, and ccf). Phylogenetic analysis of the PFGE profiles identified several small clusters within E. faecalis isolates, one of which included isolates of all three hospitals. Fifty-six (73%) isolates occurred as unique, patient-specific clones. Several PFGE types were associated with shared features in their resistance patterns, indicating spread between and within wards. Finally, enterococci from this study and previous isolates from cheeses were examined by PFGE typing. The comparison of PFGE profiles from human and food isolates resulted in clusters of genetically strong related strains, which suggests high similarities of the enterococcal community composition of these two environments. A possible spread of the enterococcal isolates through the food supply cannot be excluded.

Antimicrobial resistance of Yersinia enterocolitica strains from human patients, pigs and retail pork in Switzerland.

To obtain basic data for future resistance monitoring programs, 386 Yersinia enterocolitica strains from human patients, raw retail pork and pig feces were tested for their susceptibilities to 16 antimicrobial agents and two antimicrobial growth promoters (carbadox and olaquindox). No strains were resistant to ceftriaxone, cefuroxime, ciprofloxacine, gentamicin, kanamycin, neomycin or polymyxin. Although in Switzerland carbadox and olaquindox were used as growth promoters for pigs for over 25 years, all strains were susceptible to them. In contrast, there were high levels of resistance to ampicillin, cefalothin and amoxicillin/clavulanic acid. Less than 10% of clinical isolates and strains from pig feces were resistant to streptomycin, sulfonamide, trimethoprim/sulfamethoxazole, tetracyclin, trimethoprim and chloramphenicol, but strains from retail pork were all susceptible to these antimicrobial agents. This finding suggested that pork is probably not a major source of Y. enterocolitica that cause human infections in Switzerland. A difference between clinical isolates and strains from pork was also shown by serotyping. Clinical isolates frequently belonged to the O3 and O9 groups whereas these two serotypes were not found in strains from pork. Resistance to multiple antimicrobial agents was rare. When examined by pulsed field gel electrophoresis (PFGE), two strains of fecal origin with an identical pattern of resistance to six antimicrobial agents were shown to be unrelated. Of four clinical isolates with resistances to five antimicrobial agents, two were of the same pulsotype. Retrospectively, it was found that these strains came from two members of the same household and thus represented a mini-outbreak.

Aeromonas bacteremia in an elderly immunocompetent patient.

We report the case of an elderly immunocompetent patient with Aeromonas hydrophila bacteremia without evidence of portal of entry. Despite several risk factors for a poor outcome, such as impaired renal function, two positive blood cultures, and community-acquired infections, the patient survived. Antimicrobial susceptibility was normal. Unknown polycystic liver disease was discovered and misdiagnosed as a hepatic abscess at the time of the bacteremia which was confirmed by repeated CT scans. Because of the absence of other risk factors for Aeromonas bacteremia, hepatic polycystic disease may take part in the onset of Aeromonas sp bacteremia as well as immunosenescence.

Successful treatment of Candida parapsilosis (fluconazole-resistant) osteomyelitis with caspofungin in a HIV patient.

Treating Candida arthritis is challenging. We report a case of Candida parapsilosis arthritis successfully treated with caspofungin. We illustrate the likelihood of severe infections due fluconazole resistant C. parapsilosis after extensive fluconazole use and discuss the role of newer antifungal agents in the treatment of arthritis due to Candida spp.

Secular trends of nocardia infection over 15 years in a tertiary care hospital.

AIMS: To assess the incidence of nocardia infection over 15 years in a tertiary care hospital. METHODS: Over a 15 year period, Nocardia spp were isolated from 20 patients hospitalised at the Geneva University Hospitals, Switzerland. RESULTS: Sixteen patients had one or more underlying conditions. The median time between symptom onset and diagnosis was 30 days. The most common initial unconfirmed diagnosis was pulmonary tuberculosis (four). The lung was involved in 16 cases, followed by the central nervous system (two) and skin (two); one patient had disseminated infection. The most common species identified was N asteroides. In vitro susceptibility testing was performed on 14 of 20 strains. All strains were susceptible to imipenem and amikacin. Initial treatment with trimethoprim/sulfamethoxazole (TMP/SMX) was started in 14 patients, although five patients had to be switched to another treatment because of side effects or lack of efficacy. A cure was observed in 15 patients, death in three, and relapse or complications in two. CONCLUSIONS: Nocardiosis can become a severe infection and mainly affects profoundly immunocompromised patients. Differential diagnosis often delays the time to diagnosis, which worsens the outcome. New diagnostic tools, such as the polymerase chain reaction, could provide more rapid and reliable results. TMT/SMX was the most commonly prescribed treatment, but needed to be changed for another treatment because of side effects or lack of efficacy in a considerable proportion of patients. Imipenem should be used as an alternative treatment for severely ill patients, and the sulfa combination for less severe infections.

Epidemiology of meningococcal disease in Switzerland, 1999-2002.

In Switzerland, immunisation against serogroup C meningococcal disease is recommended for persons at increased risk but is not included in the national vaccination programme. The aim of this study was to present the nationwide surveillance data on invasive meningococcal disease collected from 1999 to 2002, emphasising the evolution in the absence of extended vaccination. The number of reported cases of meningococcal disease peaked at 178 cases in 2000 (incidence rate of 2.5/100,000 person-years), with 61% of all cases attributed to serogroup C meningococci (incidence rate, 1.5/100,000 person-years). Since 2001, a spontaneous decrease in the reported cases was observed, resulting in an overall incidence rate of 1.4/100,000 person-years in 2002 (serogroup C cases, 0.8/100,000 person-years). On the other hand, the case-fatality rate of serogroup C cases increased to 18% in 2002, leading to an increase in the overall case-fatality rate from 8% to 14% (P>0.05). The small sample size reduces the interpretability of this observation. However, when the introduction of a generalised vaccination against serogroup C meningococcal disease is discussed, the fluctuations in the number of vaccine-preventable deaths should receive greater attention.

Severe Mycoplasma hominis infections in two renal transplant patients.

Systemic infections due to Mycoplasma hominis are rare and occur mainly in immunocompromised patients. Reported here are the cases of two renal transplant patients with peritonitis who did not respond to empirical antimicrobial treatment. Effective treatment with doxycycline was administered only after definitive identification of Mycoplasma hominis was achieved. For this identification, the new genetic amplification-sequencing method was invaluable.

External quality control of direct antigen tests to detect group A streptococcal antigen.

Presented here are the results of an external quality control survey organized by the Swiss Center for Quality Control (CSCQ) to evaluate the performance of direct antigen tests (DATs) widely used in Swiss medical practices and laboratories for the diagnosis of group A streptococcal pharyngitis. Twice yearly over a 4-year period, just over 100 participants were requested to analyze positive, weakly positive and negative samples provided to them by the CSCQ with their routinely used DATs and to send the results to the CSCQ. For 1,620 samples distributed, the CSCQ received 1,484 (91.6%) results obtained with 17 different DATs. The specificity of all DATs for negative samples was >91%. For samples containing abundant group A streptococcal antigen, sensitivities ranged from 59.1% to 95.5%; however, for samples containing low levels of antigen, the sensitivity was much lower for all DATs, ranging from 8.7% to 69.8%. Therefore, negative DAT results should be verified with well-performed cultures in order to assure the optimal care of patients with pharyngitis.

Successful treatment of pulmonary invasive aspergillosis with voriconazole in patients who failed conventional therapy.

BACKGROUND: The incidence of fungal infections, including those due to Aspergillosis species has continued to increase in recent years. Invasive aspergillosis remains an important cause of morbidity and mortality, despite therapeutics interventions. PATIENTS AND METHODS: We reported five cases of invasive pulmonary aspergillosis treated with voriconazole failing to respond to conventional treatments. RESULTS: The clinical and radiological resolution of pulmonary aspergillosis reported in these cases following therapy with voriconazole is remarkable, considering the infections had proved refractory to standard antifungal therapies. Long-term therapy (in two cases > or = 1 year, in one case 6 months) was very well tolerated by patients who were unable to tolerate other antifungal agents. CONCLUSION: Therapy with voriconazole offers a new therapeutic option for otherwise difficult-to-treat infections and the potential to significantly improve the management of Aspergillosis infections.

Caspofungin in the treatment of oropharyngeal candidiasis.

A patient with AIDS developed oropharyngeal candidiasis. Candida albicans and C. glabrata were isolated from the patient and found to be resistant to fluconazole and itraconazole in vitro. Voriconazole therapy was initiated, but discontinued when the C. albicans strain isolated from the patient was found to be resistant to it. The patient failed to respond to subsequent therapy with a combination of amphotericin B and 5-flucytosine. Therapy with caspofungin was then initiated (70 mg loading dose, followed by 50 mg/day). The patient responded favourably to caspofungin, with complete resolution of signs and symptoms.

Fungemia in HIV-infected patients: a 12-year study in a tertiary care hospital.

Opportunistic infections caused by fungi are common in human immunodeficiency virus (HIV)-infected patients. We focused on severe infections as indicated by detectable fungemia. Medical charts available for patients having positive blood cultures with fungi at the University of Geneva Hospital were retrospectively (1989 to 2000) reviewed. Of 328 patients with fungemia during the study period, 315 (96%) medical charts were accessible. Of these 315 patients, 37 (12.2%) were HIV-positive, and 13 (35.1%) died within 6 months from their episode of fungemia. This was a lower mortality rate than for the HIV seronegative patients (45.8%). The median and average age of the 34 HIV-positive patients was 37.2 years, and 24 (64.9%) were males. Cryptococcus neoformans (n = 14) and Candida albicans (n = 12) were the most frequently identified species, followed by Candida glabrata (n = 3), of which 3 were mixed C. albicans + C. glabrata, Histoplasma capsulatum (n = 2), and Penicillium marneffei (n = 2). The frequency decreased significantly (p < 0.007) from the time period 1993 to 1996 (n = 21) to the period 1997 to 2000 (n = 6). Fungemias in HIV-infected patients have declined significantly since 1996. This coincides with the introduction of highly active antiretroviral therapy (HAART).

Waldenström's disease complicated by recurrent meningococcal arthritis.

Meningococcal arthritis is rare. We report a patient in whom a first episode of meningococcal arthritis revealed Waldenström's disease and who experienced a second episode of meningococcal arthritis 8 years later. We suggest that an impaired immune response secondary to Waldenström's disease favored the recurrence of meningococcal arthritis.

Evaluation of the Bactec 960 automated nonradiometric system for isolation of mycobacteria from clinical specimens.

The Bactec MGIT 960 system (Becton Dickinson, USA), designed for the culture of mycobacteria, was compared with the Bactec 460 instrument and culture on two solid egg-based media using a total of 1024 clinical specimens. Mycobacteria could be identified from 99 (9.7%) specimens, 89 (90%) of which were identified by the Bactec 960 system, 90 (91%) by the Bactec 460 system, and 82 (83%) by culture on the two egg-based media. The Bactec 960 cultures became positive an average of 16.7 days after specimen collection, the Bactec 460 cultures 14.9 days after collection, and the cultures on egg-based media 26.2 days after collection. The Bactec 960 is a compact and highly automated nonradiometric system that may replace the Bactec 460 system.

Effect of delayed infection control measures on a hospital outbreak of methicillin-resistant Staphylococcus aureus.

All patients positive for methicillin-resistant Staphylococcus aureus (MRSA) at the University Hospitals of Geneva, Switzerland, between 1989 and 1997 (N = 1771) were included in a cohort study to evaluate the consequences of delayed containment of a hospital-wide outbreak occurring during a 4-year absence of MRSA control measures. The effects of efforts to control both the MRSA reservoir and the number of bacteraemic patients were assessed. Intensive infection control measures were initiated in 1993 and included patient screening, on-site surveillance, contact isolation, a computerized alert system, and hospital-wide promotion of hand hygiene. An increase in the rate of new MRSA-infected or -colonized patients was observed between 1989 and 1994 (from 0.05 to 0.60 cases per 100 admissions), which subsequently decreased to 0.24 cases in 1997 (P<0.001). However, the proportion of laboratory-documented methicillin-resistant isolates among all S. aureus showed little variation in the years from 1993 onwards (range, 19-24%), reflecting the result of an increase in the number of screening cultures. The annual number of patients with MRSA bacteraemia strongly correlated with the hospital-wide prevalence of MRSA patients (R(2)= 0.60; P = 0.01) and the rate of new MRSA patients (R(2)= 0.97; P<0.001). Consequently, the attack rate of nosocomial MRSA bacteraemia served as an excellent marker for the MRSA patient reservoir. In conclusion, despite delayed implementation, infection control measures had a substantial impact on both the reservoir of MRSA patients and the attack rate of MRSA bacteraemia.

Three cases of cutaneous sarcoidosis: search for bacterial agent by the 16S RNA gene analysis and treatment with antibiotics.

BACKGROUND: The aetiology of sarcoidosis remains controversial. An infectious origin is often discussed, but only anti-inflammatory or immunosuppressive treatment is recommended. OBJECTIVES: To investigate the hypothesis of bacterial origin by treating cutaneous sarcoidosis with antibiotics. METHODS: Patients with chronic cutaneous sarcoidosis, unresponsive to the usual treatment and not requiring systemic corticotherapy, were given combined antibiotherapy for 6 months. Search for bacterial DNA by amplification and sequencing of the 16S ribosomal RNA gene in skin biopsies of lesions before and after antibiotherapy was done. RESULTS: Three patients received a combined treatment with clarithromycin 1 g/day and ciprofloxacin 1 g/day. No clinical changes occurred in 2 cases and transient worsening in 1. Amplification for bacterial DNA was positive in all skin biopsies. The sequencing of this DNA could not identify a unique bacterial species. CONCLUSION: No evident bacterial origin could be demonstrated; however, this approach should be extended to more patients.