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.

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.

Quantitative cultures of biopsy specimens from cutaneous cellulitis.

To study the microbiologic features of cutaneous cellulitis prospectively, quantitative biopsy cultures were carried out in 25 patients who were hospitalized for an untreated cutaneous cellulitis. Biopsy specimens were obtained from both the center and the advancing edge of erythema. Only nine biopsy specimens (three central and six peripheral) (18%) of 50 yielded pathogens. Needle aspiration cultures were performed in seven cases: two yielded pathogens (28.5%). The density of microorganisms was low, ranging from less than 80 colony-forming units (CFUs) per gram of tissue to 1360 CFUs/g of tissue, except next to the edge of an ulcer (two cases), where densities reached 3.2 x 10(6) CFUs/g of tissue. Cutaneous cellulitis shows a discrepancy between the low density of microorganisms and the intensity of the inflammation. A factor other than infection must be implicated. This might be lymphatic failure, which is found in 72% of patients.

Automatic alerts for methicillin-resistant Staphylococcus aureus surveillance and control: role of a hospital information system.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an escalating problem in hospitals worldwide. The hospital reservoir for MRSA includes recognized and unrecognized colonized or infected patients, as well as previously colonized or infected patients readmitted to the hospital. Early and appropriate infection control measures (ICM) are key elements to reduce MRSA transmission and to control the hospital reservoir. OBJECTIVE: To describe the role of an expert system applied to the control of MRSA at a large medical center (1,600 beds) with high endemic rates. METHODS: The University Hospital of Geneva has an extended hospital information system (HIS), DIOGENE, structured with an open distributed architecture. It includes administrative, medical, nursing, and laboratory applications with their relational databases. Among available patient databases, clinical microbiology laboratory and admission-discharge-transfer (ADT) databases are used to generate computer alerts. A laboratory alert (lab alert) is printed daily in the Infection Control Program (ICP) offices, listing all patients with cultures positive for MRSA detected within the preceding 24 hours. Patients might be either newly detected patients colonized or infected with MRSA, or previously recognized MRSA patients having surveillance cultures. The ICP nurses subsequently go to the ward or call the ward personnel to implement ICM. A second alert, the "readmission alert," detects readmission to the hospital of any patient previously colonized or infected with MRSA by periodic queries (q 1 min) to the ADT database. The readmission alert is printed in the ICP offices, but also forwarded with added guidelines to the emergency room. RESULTS: During the first 12 months of application (July 1994 to June 1995), the lab alert detected an average of 4.6 isolates per day, corresponding to 314 hospital admissions (248 patients); the use of this alert saved time for the ICP nurses by improving work organization. There were 438 readmission alerts (1.2 alerts per day) over the study period; of 347 patients screened immediately upon readmission, 114 (33%) were positive for MRSA carriage. Delayed recognition of readmitted MRSA carriers decreased significantly after the implantation of this alert; the proportion of MRSA patients recognized at the time of admission to the hospital increased from 13% in 1993 to 40% in 1995 (P < .001). CONCLUSIONS: Hospital information system-based alerts can play an important role in the surveillance and early prevention of MRSA transmission, and it can help to recognize patterns of colonization and transmission.

Subcutaneous continuous infusion of ifosfamide and cyclophosphamide in ambulatory cancer patients: bioavailability and feasibility.

The oxazaphosphorines ifosfamide (IFO) and cyclophosphamide (CTX) are standard alkylating agents. Both drugs show an increased therapeutic index when given as a fractionated dosage over several days. Maximal fractionation is achieved by continuous infusion. We have studied the feasibility and bioavailability of a subcutaneously (s.c.) administered isotonic and neutral (pH 7) solution of IFO (10 h up to 5 days infusion) and CTX (12-24 h infusion) in patients with advanced cancer. A portable disposable gas-driven infusor syringe was used for ambulatory patients. Our results show 90%-100% bioavailability of s.c. IFO and CTX. The isotonic solution of IFO and CTX (pH 7) showed no significant local toxicity (one local infection in 51 cycles) during or after s.c. administration of 33 cycles with IFO and 18 with CTX. Haematotoxicity of both drugs was equal after s.c. and i.v. application. For IFO-treated patients no uro- or neurotoxicity was observed. We conclude that this novel continuous s.c. oxazaphosphorine infusion over a prolonged period is a rational, well-tolerated and economic way of delivering this drug on an outpatient basis.

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.

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.

A validation study on the intraobserver and interobserver reproducibility of renal artery duplex ultrasound.

Aim of the present study was to evaluate intraobserver and interobserver reproducibility of direct renal artery Doppler velocimetry. Healthy volunteers were evaluated by one examiner on three separate occasions and by three different examiners in a single day. Peak systolic velocities of the aorta (PSV.Ao) and proximal renal arteries (PSV.RA) were taken at an optimal angle below 60 degrees. The renal-to-aortic ratio (RAR) was calculated dividing PSV.RA by PSV.Ao. Mean values +/- 2 SD were 85 +/- 34 (49-150) cm/s for the PSV.RA, 38 +/- 20 (0-60 degrees) for the Doppler angle of insonation, 102 +/- 37 (63-153) cm/s for the PSV.Ao, and 0.85 +/- 0.41 (0.49-1.58) for the RAR. Correlation coefficients and coefficient of variation were 0.64-0.82/7.8%-10.1% (PSV.RA), 0.75-0.82/9.9%-13.8% (RAR) for intraobserver evaluations; and 0.79-0.80/7.7%-12.5% (PSV-RA), 0.65-0.78/9.5%-12.3% (RAR) for interobserver evaluations. Reliable results of direct renal artery Doppler velocimetry confirm clinical applicability and suitability for repeated measurements after catheter-based interventions or surveillance of low-grade stenoses.

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).

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.

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.

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.

[Vestibuloplasty with Kirschner wire fixation]. / Vestibulumplastik mit Kirschner-Draht-Fixation.

We present a new method of fixation for creation of the vestibular sulcus in cases of open or closed submucous vestibuloplasty. Kirschner-wires (diameter 0.5 mm) are drilled through the mucous membrane into the bone. The wires keep the hand cut oval elastic sheets in place to adapt the mucous membrane to the periosteum at the deepest point of the vestibule respectively. Advantages of the method in comparison to other fixation techniques are discussed.

Comparative evaluation of the BCB Roche and Oxoid Signal blood culture systems.

The agar-slide blood culture system BCB Roche was compared with the Oxoid Signal blood culture system using 2,266 paired blood cultures. A total of 271 (12%) paired sets were culture-positive, including 222 (9.8%) yielding pathogens associated with septicemia and 50 (2.2%) yielding likely contaminants. In the recovery of the total 235 isolates considered as pathogens, the BCB Roche system yielded 202 (85.9%), the Oxoid Signal 211 (89.8%); 178 (75.7%) were cultured by both systems. There was no statistically significant difference between the two systems in their sensitivity, contamination-rate and detection time, except for gram-positive organisms, which were detected earlier by the Oxoid Signal system. Both systems performed well and were easy to handle.

[Osteomyelitis in congenital analgesia]. / Osteomyelitis bei kongenitaler Analgie.

Presentation of a case of a congenital analgia, who showed as a complication a chronical osteomyelitis of the mandible with formation of sequester and fracture. Partial resection of the mandible and immediate reconstruction was done performing simultaneously a rebuilding of the atrophied alveolus by the use of split ribs and fixation with a long miniplate.

Comparison of BacT/Alert with Signal blood culture system.

The BacT/Alert (Organon Teknika Corp., Durham, N.C.) is an automated blood culture system. It is based on the detection of CO2 by means of a colorimetric sensor internally attached to the bottom of culture bottles. The aerobic and anaerobic media of this system were compared with one bottle of the Signal system (Oxoid Ltd., Hampshire, United Kingdom). At bedside, 20 ml of blood was drawn from each adult patient. The two BacT/Alert bottles were inoculated with 5 ml of blood each; the Signal bottle was inoculated with 10 ml. A total of 5,284 sets (2,483 patients; 2.1 cultures per patient) consisting of three bottles each were evaluated, of which 781 sets (14.8%) revealed microorganisms (n = 892); 642 of these were considered to be pathogenic. Significantly more (P < 0.0001) pathogens were isolated from the two BacT/Alert bottles together (n = 584) than from the single Signal bottle (n = 515). Escherichia coli (P = 0.007), gram-negative bacteria other than members of the family Enterobacteriaceae or Pseudomonas spp. (P = 0.006), and yeasts (P = 0.02) were isolated more often from both or either BacT/Alert bottle. Comparing the systems in terms of 388 different organisms per septic episode, the difference between BacT/Alert and Signal was significant for the total number of septicemia cases (P = 0.003). More contaminants grew in the BacT/Alert system (173 versus 116; P = 0.0001). False-positive indications were more frequent in the BacT/Alert system, 198 (3.7%) aerobic bottles and 57 (1.1%) anaerobic bottles, than in the Signal bottles, 24 (0.5%) bottles. Pathogens could be detected significantly earlier (P < 0.0001) in the BacT/Alert system than in the Signal system. The BacT/Alert instrument with two bottles allowed earlier detection as well as the isolation of more microorganisms than the manual, one-bottle Signal system.