In spite of significant changes in the spectrum of organisms causing nocosomial infections in intensive care units (ICUs), Pseudomonas aeruginosa has held a nearly unchanged position as an important pathogen. Today, the organism is isolated as the second most frequent organism causing ventilator-associated pneumonia, and the third or fourth most frequent pathogen causing septicemia, urinary tract infections, and surgical wound infections. In the past, horizontal transmissions were regarded as the most relevant route of strain acquisition. However, during the last 10 years, a significant proportion of P. aeruginosa isolates were demonstrated to stem from ICU water sites. Studies using molecular typing techniques have shown that up to 50% (in one study 92%) of nosocomial P. aeruginosa acquisitions may result from transmission through tap water. Additional proof of concept of waterborne infection comes from the reports of three recent studies that infection rates may be lowered significantly by eliminating colonized tap water sources or interrupting transmission chains from water sites.

Several outbreaks of Pseudomonas aeruginosa have been published in neonatal and pediatric patients, but no systematic analysis is available. Medline and outbreak-database search, systematic analysis of outbreak reports (confirmed by genotyping). Twenty-four studies were included. Outbreaks caused by P. aeruginosa resulted in high morbidity (median clinical infection rate: 68%; range: 0-100%), mortality (median 27%; 0-100%) and resource consumption in neonatal and pediatric inpatient facilities. In most cases, these outbreaks indicate certain breaches in basic hygienic practices or are due to the persistence of P. aeruginosa in environmental vectors and reservoirs (tap water, medical devices, and fomites). The majority of the reported isolates displayed multi-resistance to first-line antibiotics. The clinical observation of two or more temporally related cases of nosocomial P. aeruginosa infections should raise the suspicion of an outbreak particularly in high-risk pediatric patient populations (neonatal intensive care unit, pediatric intensive care unit, oncology) and when the isolate displays resistance to two or more first-line antibiotics. Strict hygienic barrier precautions should immediately be implemented, re-educated and supervised. Well-planned environmental culturing should be performed, paying special attention to water, water outlets, sinks and other wet areas, to identify environmental reservoirs. A water safety plan based on the WHO Guidelines for Drinking Water Quality must be introduced. The current strategy of empiric antibiotic treatment should be investigated by an infectious diseases' specialist. Genotyping of the isolates by pulse-field gel electrophoresis should be performed, but any interventions to interrupt further nosocomial spread should be carried out without waiting for the results.

BACKGROUND:Mupirocin is a natural antibiotic from Pseudomonas fluorescens which is available as a 2% ointment. The drug has been used mainly for topical treatment of the nasal vestibulum in patients carrying methicillin-resistant Staphylococcus aureus (MRSA). However, mupirocin is also active against methicillin-sensitive S. aureus. Nasal colonization with S. aureus has been identified as a significant risk factor for surgical site infection (SSI).METHODS:Randomized trials and sequential cohort studies investigating mupirocin nasal treatment for prophylaxis of SSI in elective surgery in comparison with placebo or no treatment were found by Medline review and additional manual search. Evaluable studies were analyzed regarding the influence of mupirocin on the rate of all SSIs and, specifically, of SSIs due to S. aureus. The effect in cardiosurgical patients was analyzed in detail.RESULTS:Four randomized and seven sequential open cohort studies were analyzed. Study design and mupirocin application schemes varied considerably. Three out of 5 studies carried out in cardiac surgery patients showed a significant reduction in sternotomy site infections. However, all three studies were open sequential cohort studies. By contrast, the only prospective, randomized, double-blind study in cardiosurgical patients showed no benefit of mupirocin. In other surgical disciplines, results were inconclusive or negative. Two studies specifically addressing the prevention of SSIs due to MRSA showed a significant effect of mupirocin on postsurgical infections due to this organism.CONCLUSIONS:Because of the heterogeneity of the studies and the variability of results, no recommendation can be given for the general use of mupirocin in elective surgical patients. Specifically, because of the negative result of a recently published high-quality study, no recommendation can be made for the use of mupirocin in cardiosurgical patients. By contrast, eradication of MRSA before surgery appears to lower SSI rates due to MRSA and is therefore recommended.

Background: The tested device is a new connecting tool for infusion systems that has been designed to replace conventional single-use stopcocks. Because outbreaks of bloodstream infections have been observed during the use of similar connectors in the United States, we examined the microbiological safety of the connecting device after artificial contamination in the laboratory setting and during routine clinical use.Methods: In the first part of the study, the new device was tested in 3 types of in vitro experiments. in the second part of the study, surgical intensive care patients had their entry ports capped with novel devices (n = 27) or with conventional stopcocks (n = 32), and samples of infusion fluids and swabs from entry ports were taken after completion of infusion periods.Results: The new device did not perpetuate bacterial contaminations in spite of high artificial inocula in the in vitro experiments. Microbial contamination rates after 96 hours of infusion therapy for the novel connecting tool versus conventional stopcock groups were as follows: swabs from 3-way ports, 6/129 versus 1/111 rest fluid from infusion lines, 0/20 versus 1/22 rest fluid from infusion bottles, 2/196 versus 2/208 rest fluid from perfusor syringes, 7/180 versus 6/142 (all differences not significant).Conclusion: The novel connecting device was microbiologically safe and did riot increase microbial contamination rates of intravenous infusion systems.

Infections due to Klebsiella pneumoniae and other Klebsiella spp. are a leading cause of hospital-associated morbidity, especially in the intensive care setting. In this study, the hypothesis that normal human sera contain sufficient concentrations of K-antigen-specific antibodies to promote phagocytic killing of encapsulated, highly virulent Klebsiella organisms was tested. K2-antigen-specific IgG and IgM antibodies were detected in each of 10 normal sera, and such antibodies were functionally active in a phagocytic killing assay. Phagocytosis depended critically on sufficient numbers of neutrophils and was impaired by the presence of soluble Klebsiella capsular polysaccharide (CPS). Thus, insufficient numbers of neutrophils and circulation of soluble CPS but not lack of K-specific antibodies may be detrimental in Klebsiella sepsis. The efficacy of hyperimmune sera might be based not on enhancement of phagocytosis but on the neutralization of these detrimental effects of circulating CPS and LPS.

To provide a database for the development of an O-antigen-polysaccharide-containing vaccine against Klebsiella spp., we examined the O-antigen seroepidemiology of 378 Klebsiella clinical isolates collected prospectively in two university centers. Strains were typed by competitive enzyme-linked immunosorbent assay with rabbit antisera specific for serogroups O1 to O12 and monoclonal antibodies (MAbs) specific for serogroups O1, O2ab, O2ac, and the genus-specific core antigen. The numbers of isolates (percentages) of individual O serogroups were as follows: 148 (39.2) for serogroup O1, 40 (10.6) for serogroup O2ab, 4 (1.1) for serogroup O2ac, 89 (23.6) for serogroup O3, 2 (0.5) for serogroup O4, 32 (8.5) for serogroup O5, none for serogroups O7, O9, and O12, and 21 (5.6) for serogroup O11. Forty-two (11.1) of the strains were non-O-typeable. O-serogroup distributions were virtually identical between isolates from invasive infections and those from noninvasive infections or colonizations. A vaccine containing the O-specific polysaccharides of serogroups O1, O2ab, O3, and O5 would cover 82% of clinically occurring O-antigen specificities. Three hundred thirty-eight of 378 isolates (89.4%) reacted with the genus-specific MAb V/9-5, which recognizes an epitope of the outer core region of Klebsiella lipopolysaccharide. Antibodies directed against this epitope may represent a further alternative for O-antigen-targeted immunoprophylaxis of Klebsiella infections. These data support further experimental investigations on the protective potential of O-antigen-based vaccines and/or hyperimmune globulins in Klebsiella infection.

ABSTRACT It is generally assumed that the antibiotic prescription policy of a hospital has a significant impact on bacterial resistance rates; however, few studies are available to support this concept with valid statistical data. During a 3-year period from 1997 to 2000, we monitored the consumption of β-lactam and other antibiotics with known activity against Pseudomonas aeruginosa in a 600-bed community hospital. Monthly isolations of P. aeruginosa were assessed, and resistance rates were recorded. Partial correlation coefficients between consumption and resistance rates were determined, taking into account possible associations with other variables such as seasonal effects and transfers from other hospitals. A total of 30 ± 7 novel P. aeruginosa strains per month were isolated without epidemic clustering. Prescriptions of imipenem varied significantly during the study period, while prescriptions of other antipseudomonal agents were stable, with the exception of an increase in piperacillin-tazobactam prescriptions. Rates of resistance of P. aeruginosa to the antimicrobial agents used showed a time course similar to figures for imipenem consumption. Monthly rates of resistance to imipenem (partial correlation coefficient [cc], 0.63), piperacillin-tazobactam (cc, 0.57), and ceftazidime (cc, 0.56) were significantly associated with imipenem prescription rates in the same or the preceding month, while consumption of ceftazidime or piperacillin-tazobactam had no apparent association with resistance. Among the variables investigated, imipenem consumption was identified as the major factor associated with both carbapenem and β-lactam resistance in endemic P. aeruginosa. Periods of extensive imipenem use were associated with significant increases in resistance. Our data support the concept that a written antibiotic policy which balances the use of various antibiotic classes may help to avoid disturbances of a hospital's microbial sensitivity patterns.

. Antibiotic-induced release of bacterial cell wall components can have immediate adverse effects for the patient. This article reviews the data on endotoxin release after initiation of antibiotic therapy and its role in the pathogenesis of sepsis and septic shock. Antibiotics differ in their potential to liberate endotoxins from bacterial cell walls. When used for treatment of systemic Gram-negative infection, some classes of β-lactam antibiotics lead to markedly increased levels of free endotoxins while treatment with carbapenems and aminoglycosides produces relatively low amounts of endotoxins. Antibiotics that induce the formation of long, aberrant bacterial cells before effectively killing the microorganisms show the highest degree of endotoxin liberation. There is increasing evidence from animal models and clinical studies of sepsis that the antibiotic-mediated release of biologically active cell wall components derived from Gram-positive, Gram-negative or fungal organisms is associated with a rapid clinical deterioration.

Objective: Establishment of a case definition for invasive candidosis in postsurgical intensive care patients. Methods: During the period of 1996-1999, 8 cases of invasive candidosis were observed on a surgical intensive care unit. Patient records were evaluated with respect to diagnostic criteria and response to antimycotic therapy. Results: Patients included 3 women and 5 men with a mean age of 62.7 (37-85) years. Candida peritonitis (n = 6) occurred after surgery or perforation of the intestinal tract, and Candida pneumonia was due to artifical ventilation (n = 3). C. albicans was isolated in all 8 cases, but mixed infections with other Candida spp. occurred in 3 cases. The Candida serum antigen test yielded a positive result in only 2/8 cases. I.v. therapy with fluconazole was successful in 7 cases, one patient with severe initial disease died with ongoing infection. With the exception of the lethal case, all patients showed a diagnostic serum antibody test, proving systemic candida infection. Conclusion: Based on the case descriptions, we propose the following definition of invasive candidosis: (1) Clinical signs of infection after surgery, (2) absence of bacterial pathogens and/or failure to respond to systemic antibiotics, (3) cultivation of Candida spp. from normally sterile sites or abundant growth in tracheal aspirate, (4) response to antimycotic therapy and (5) diagnostic serum antibody test. This definition proved to be valid for our patients and could be used as an inclusion criterion for future clinical studies of serodiagnosis of Candida infection or antimycotic chemotherapy.

Based on the case descriptions, we propose the following definition of invasive candidosis: (1) Clinical signs of infection after surgery, (2) absence of bacterial pathogens and/or failure to respond to systemic antibiotics, (3) cultivation of Candida spp. from normally sterile sites or abundant growth in tracheal aspirate, (4) response to antimycotic therapy and (5) diagnostic serum antibody test. This definition proved to be valid for our patients and could be used as an inclusion criterion for future clinical studies of serodiagnosis of Candida infection or antimycotic chemotherapy.