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Objective: To study the acquisition and cross-transmission of Staphylococcus aureus in different intensive care units (ICUs)., Methods: We performed a multicenter cohort study. Six ICUs in 6 countries participated. During a 3-month period at each ICU, all patients had nasal and perineal swab specimens obtained at ICU admission and during their stay. All S. aureus isolates that were collected were genotyped by spa typing and multilocus variable-number tandem-repeat analysis typing for cross-transmission analysis. A total of 629 patients were admitted to ICUs, and 224 of these patients were found to be colonized with S. aureus at least once during ICU stay (22% were found to be colonized with methicillin-resistant S. aureus [MRSA]). A total of 316 patients who had test results negative for S. aureus at ICU admission and had at least 1 follow-up swab sample obtained for culture were eligible for acquisition analysis., Results: A total of 45 patients acquired S. aureus during ICU stay (31 acquired methicillin-susceptible S. aureus [MSSA], and 14 acquired MRSA). Several factors that were believed to affect the rate of acquisition of S. aureus were analyzed in univariate and multivariate analyses, including the amount of hand disinfectant used, colonization pressure, number of beds per nurse, antibiotic use, length of stay, and ICU setting (private room versus open ICU treatment). Greater colonization pressure and a greater number of beds per nurse correlated with a higher rate of acquisition for both MSSA and MRSA. The type of ICU setting was related to MRSA acquisition only, and the amount of hand disinfectant used was related to MSSA acquisition only. In 18 (40%) of the cases of S. aureus acquisition, cross-transmission from another patient was possible., Conclusions: Colonization pressure, the number of beds per nurse, and the treatment of all patients in private rooms correlated with the number of S. aureus acquisitions on an ICU. The amount of hand disinfectant used was correlated with the number of cases of MSSA acquisition but not with the number of cases of MRSA acquisition. The number of cases of patient-to-patient cross-transmission was comparable for MSSA and MRSA.

A hospital-wide increase in the number of patients with aminoglycoside-resistant Enterobacter cloacae (AREC) isolated from clinical cultures was detected in December 2002 using a classical surveillance system (CSS). CSS refers to a strategy based on the recognition of an increased incidence of a species with a particular antibiogram at certain wards in a limited period. Since clonal spread was suspected, hospital records were reviewed for E. cloacae culture-positive patients. Based upon genotyping of 139 clinical E. cloacae isolates from 80 patients, it was concluded that 53 patients had had clinical cultures with a single AREC clone since April 2001. Determinants for unnoticed spread were investigated retrospectively, as was the possibility that a computer-assisted surveillance method would have detected this outbreak at an earlier stage. Determinants associated with late detection of clonal spread were the following: (i) the absence of a hospital-wide increase in incidence of E. cloacae cases for 1.5 years, (ii) the long time interval between cases, (iii) the hospital-wide occurrence of new cases, due to a high number of patient transfers between wards, (iv) the large variety of clinical sites, and (v) the high variability of antibiograms (n = 33). Retrospective application of a recently described computer-assisted surveillance method as well as an "in-house"-developed algorithm resulted in earlier detection of the outbreak of 6 and 12 months, respectively. These findings suggest that computerized tools for surveillance may recognize resistance trends that are too complex to be detected by manual review and indicate the need for prospective evaluation of such algorithms.

Nosocomial pneumonia or hospital-acquired pneumonia (HAP) causes considerable morbidity and mortality. It is the second most common nosocomial infection and the leading cause of death from hospital-acquired infections. In 1996 the American Thoracic Society (ATS) published guidelines for empirical therapy of HAP. This review focuses on the literature that has appeared since the ATS statement. Early diagnosis of HAP and its etiology is crucial in guiding empirical therapy. Since 1996, it has become clear that differentiating mere colonization from etiologic pathogens infecting the lower respiratory tract is best achieved by employing bronchoalveolar lavage (BAL) or protected specimen brush (PSB) in combination with quantitative culture and detection of intracellular microorganisms. Endotracheal aspirate and non-bronchoscopic BAL/PSB in combination with quantitative culture provide a good alternative in patients suspected of ventilator-associated pneumonia. Since culture results take 2-3 days, initial therapy of HAP is by definition empirical. Epidemiologic studies have identified the most frequently involved pathogens: Enterobacteriaceae, Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus ('core pathogens'). Empirical therapy covering only the 'core pathogens' will suffice in patients without risk factors for resistant microorganisms. Studies that have appeared since the ATS statement issued in 1996, demonstrate several new risk factors for HAP with multiresistant pathogens. In patients with risk factors, empirical therapy should consist of antibacterials with a broader spectrum. The most important risk factors for resistant microorganisms are late onset of HAP (>/=5 days after admission), recent use of antibacterial therapy, and mechanical ventilation. Multiresistant bacteria of specific interest are methicillin-resistant S. aureus (MRSA), Pseudomonas aeruginosa, Acinetobacter calcoaceticus-baumannii, Stenotrophomonas maltophilia and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. Each of these organisms has its specific susceptibility pattern, demanding appropriate antibacterial treatment. To further improve outcomes, specific therapeutic options for multiresistant pathogens and pharmacological factors are discussed. Antibacterials developed since 1996 or antibacterials with renewed interest (linezolid, quinupristin/dalfopristin, teicoplanin, meropenem, new fluoroquinolones, and fourth-generation cephalosporins) are discussed in the light of developing resistance.Since the ATS statement, many reports have shown increasing incidences of resistant microorganisms. Therefore, one of the most important conclusions from this review is that empirical therapy for HAP should not be based on general guidelines alone, but that local epidemiology should be taken into account and used in the formulation of local guidelines.

A multilocus sequence typing (MLST) scheme was developed for Klebsiella pneumoniae. Sequences of seven housekeeping genes were obtained for 67 K. pneumoniae strains, including 19 ceftazidime- and ciprofloxacin-resistant isolates. Forty distinct allelic profiles were identified. MLST data were validated against ribotyping and showed high (96%) discriminatory power. The MLST approach provides unambiguous data useful for the epidemiology of K. pneumoniae isolates.

A rapid method combining gyrA PCR-restriction fragment length polymorphism analysis, parC PCR and adonitol fermentation was developed to identify Klebsiella pneumoniae phylogenetic groups KpI, KpII and KpIII. Analysis of 420 clinical isolates from 26 hospitals showed that the three groups were widespread geographically. KpI comprised 80.3% of 305 isolates from blood and 82.2-97.2% of isolates from other clinical sources. KpIII was never found among isolates from urinary tract infections. KpI isolates from blood were generally less susceptible than KpIII isolates to the ten antimicrobial agents tested, with KpII being intermediate. The frequencies of ceftazidime resistance were 21.6% and 8.6% in KpI and KpIII isolates, respectively (p 0.01).

Background and Objective: The benefit of screening healthcare workers (HCWs) at risk for methicillin-resistant Staphylococcus aureus (MRSA) carriage and furloughing MRSA-positive HCWs to prevent spread to patients is controversial. We evaluated our MRSA program for HCWs between 1992 and 2002., Setting: A university medical center in The Netherlands, where methicillin resistance has been kept below 0.5% of all nosocomial S. aureus infections using active surveillance cultures and isolation of colonized patients., Design: HCWs caring for MRSA-positive patients or patients in foreign hospitals were screened for MRSA. MRSA-positive HCWs had additional cultures, temporary exclusion from patient-related work, assessment of risk factors for persisting carriage, decolonization therapy with mupirocin intranasally and chlorhexidine baths for skin and hair, and follow-up cultures., Results: Fifty-nine HCWs were colonized with MRSA. Seven of 840 screened employees contracted MRSA in foreign hospitals; 36 acquired MRSA after contact with MRSA-positive patients despite isolation precautions (attack rate per outbreak varied from less than 1% to 15%). Our hospital experienced 17 MRSA outbreaks, including 13 episodes in which HCWs were involved. HCWs were index cases of at least 4 outbreaks. In 8 outbreaks, HCWs acquired MRSA after caring for MRSA-positive patients despite isolation precautions., Conclusion: Postexposure screening of HCWs allowed early detection of MRSA carriage and prevention of subsequent transmission to patients. Where the MRSA prevalence is higher, the role of HCWs may be greater. In such settings, an adapted version of our program could help prevent dissemination.

Objectives: To determine incidence rates of hospital-acquired infections and to develop preventive measures to reduce the risk of hospital-acquired infections., Methods: Prospective surveillance for hospital-acquired infections was performed during a 5-year period in the wards housing general and vascular, thoracic, orthopedic, and general gynecologic and gynecologic-oncologic surgery of the University Medical Center Utrecht, the Netherlands. Data were collected from patients with and without infections, using criteria of the Centers for Disease Control and Prevention., Results: The infection control team recorded 648 hospital-acquired infections affecting 550 (14%) of 3,845 patients. The incidence density was 17.8 per 1,000 patient-days. Patients with hospital-acquired infections were hospitalized for 19.8 days versus 7.7 days for patients without hospital-acquired infections. Prolongation of stay among patients with hospital-acquired infections may have resulted in 664 fewer admissions due to unavailable beds. Different specialties were associated with different infection rates at different sites, requiring a tailor-made approach. Interventions were recommended for respiratory tract infections in the thoracic surgery ward and for surgical-site infections in the orthopedic and gynecologic surgery wards., Conclusions: Surveillance in four surgical wards showed that each had its own prominent infection, risk factors, and indications for specific recommendations. Because prospective surveillance requires extensive resources, we considered a modified approach based on a half-yearly point-prevalence survey of hospital-acquired infections in all wards of our hospital. Such surveillance can be extended with procedure-specific prospective surveillance when indicated.

Two burns patients who were transferred to the Central Military Hospital Utrecht from a foreign hospital, were found to be colonised with MRSA. During their 5-week hospitalisation, 21 healthcare workers and one patient became colonised with the same MRSA strain, despite isolation precautions. The department was closed for 29 days; 96 admissions were cancelled and 1411 screening cultures for MRSA were performed. Colonised healthcare workers were temporarily unable to work and additional costs were incurred for disposables and cleaning procedures. The resultant bill for this outbreak was approximately [symbol: see text] 122,500. MRSA outbreaks occur in hospitals with some degree of regularity, but the strong dispersal during this epidemic was exceptional. The transfer of possible MRSA-colonised patients from hospitals outside of the Netherlands sometimes faces opposition due to the considerable demands it makes on a hospital's personnel, organisation and finances. If this were to be compensated, then the currently successful Dutch MRSA policy could be coupled with a willingness to accept patients from hospitals outside of the Netherlands.

Although the Dutch policy to eradicate methicillin-resistant Staphylococcus aureus (MRSA) is very strict compared to policies employed in other countries, it has proven to be successful epidemiologically (incidence of MRSA in the Netherlands, <0.5%). The present study was performed to investigate both the financial and the logistical consequences of this strict, so-called "search and destroy" policy in the Netherlands. The data were based on a 10-year survey (1991-2000) of screening, surveillance, and outbreaks at the University Medical Center Utrecht. The consequences of the policy were determined by a panel comprising physicians from the Department of Surgery, the Department of Medical Microbiology, Subdivision Hospital Hygiene and Infection Prevention, the Department of Pharmacy, and Household Services. The costs associated with the policy were also calculated, including those for additional (disposable) material, cultures, specific medication, decontamination, and closing of the wards. Over the course of the 10 years, implementation of the MRSA policy resulted in more than 2,265 lost hospitalization days. In addition, the wards had to be closed 48 times, 29 healthcare workers had to temporarily discontinue working, and 78,000 additional cultures had to be performed. The total cost reached 6 million Dutch guilders (euro 2,800,000). The financial and logistical consequences were then compared to those in a hypothetical situation without the "search and destroy" policy. In such a situation, the hospital would be faced with an increased incidence of MRSA, vancomycin intermediate-susceptible Staphylococcus aureus, and vancomycin-resistant enterococci. The costs associated with the use of alternative antibiotics, required in a scenario of high endemic-level MRSA, would be at least twice as high as the costs expended in the actual situation, thus demonstrating that a strict MRSA policy is financially worthwhile.

Background and Objective: In the Netherlands, the prevalence of methicillin resistance among Staphylococcus aureus isolates has been kept to less than 1% by using active screening programs and isolation. At the University Medical Center Utrecht (UMCU), an active screening program for methicillin-resistant S. aureus (MRSA) in the surgical intensive care unit (ICU) was implemented in 1986. Between 1992 and 2001, only 6 patients with MRSA were admitted to the surgical ICU. However, 4 of these 6 strains were able to spread to 23 other patients and 15 healthcare workers (HCWs). We were surprised by the epidemic behavior of these strains and wondered whether this was exceptional for S. aureus or whether methicillin-susceptible S. aureus (MSSA) was also spreading in the ICU., Design: A 2-month, prospective, observational study to investigate the incidence and spread of MSSA in the surgical ICU of UMCU and historical data collected during a 10-year period regarding MRSA., Setting: A 10-bed surgical ICU in a 1,042-bed teaching hospital., Results: Weekly swabs revealed the presence of MSSA in 11 (24%) of 45 patients and 16 (22%) of 72 HCWs. Of all 4,105 patient-HCW contacts, there were only 21 episodes in which both the patient and the HCW were found to carry MSSA. With the use of pulsed-field gel electrophoresis, no identical strains could be identified., Conclusion: In our surgical ICU, MRSA seems to spread more easily than MSSA, probably because of selection under antibiotic pressure or a still unknown intrinsic factor within MRSA.

Multidrug resistance in gram-negative bacteria appears to be primarily the result of the acquisition of resistance genes by horizontal transfer. To what extent horizontal transfer may be responsible for the emergence of multidrug resistance in a clinical setting, however, has rarely been investigated. Therefore, the integron contents of isolates collected during a nosocomial outbreak of genotypically unrelated multidrug-resistant Enterobacteriaceae were characterized. The integron was chosen as a marker of transfer because of its association with multiresistance. Some genotypically identical isolates harbored different integrons. Grouping patients carrying the same integron yielded 6 epidemiologically linked clusters, with each cluster representing a different integron. Several patients carried multiple species harboring the same integron. Conjugation experiments with these strains resulted in the transfer of complete resistance patterns at high frequencies (10(-2) to 10(-4)). These findings provide strong evidence that the horizontal transfer of resistance genes contributed largely to the emergence of multidrug-resistant Enterobacteriaceae in this clinical setting.

Nosocomial infections play a role in quality and cost control in health care. Surveillance of these infections is the only way to gain more insight into their frequency and causes. Since the results of surveillance may lead to changes in both patient and hospital management, which are sometimes major, it is necessary that all healthcare workers involved agree on the criteria used for the diagnosis and surveillance of these complications. In order to compare the efficacy of two surveillance methods, nosocomial infections in surgical patients were registered by both the Department of Surgery (complication surveillance [CS]) and the Department of Infection Control (nosocomial infection surveillance [NIS]) at the University Medical Center Utrecht, The Netherlands, over a 2-month period. The CS team used the national criteria of the Association of Surgeons of the Netherlands and the NIS team used the international criteria of the Centers for Disease Control and Prevention, USA, to define cases of nosocomial infection. A total of 515 patients were included in both arms of the study. The CS team diagnosed 69 infections in 49 patients, and the NIS team diagnosed 64 infections in 45 patients. Of 104 total infections, 39 were diagnosed by the CS team exclusively, 35 by the NIS team exclusively and only 30 by both. The main reasons for the inconsistent results were as follows: (i) the lack of follow-up after discharge in the NIS arm, (ii) the use of clinical criteria for the definition of a nosocomial infection in the CS arm, and (iii) the use of positive cultures as part of the criteria in the NIS arm. From the perspective of infection control, the CS system cannot be recommended for the surveillance of nosocomial infections.

Between December 1999 and June 2000, an outbreak caused by Acinetobacter emerged on the neurosurgical intensive care unit of our hospital. It was shown using automated ribotyping using Eco RI and pulsed-field gel electrophoresis that the outbreak was caused by spread of a single strain, which was identified by ribotyping and amplified ribosomal DNA restriction analysis as Acinetobacter DNA group 13TU (sensu Tjernberg and Ursing). The outbreak strain, which showed no antibiotic resistance, was identified in 23 patients, five of whom developed an infection. The organism was also isolated from various environmental sites. Cross-transmission among patients continued despite contact isolation of colonized patients and reinforcement of basic disinfection procedures. Eventually, after implementation of additional stringent measures such as cohorting of positive patients and daily disinfection of the floor, the outbreak was brought under control. This study demonstrates that apart from Acinetobacter baumanii, Acinetobacter 13TU strains, even when they are fully susceptible, may cause outbreaks that are difficult to control. Correct identification to the species level of Acinetobacter by genotypic methods is necessary to get insight in the importance of the different Acinetobacter genomic species in hospital epidemiology., (Copyright 2002 The Hospital Infection Society.)

An observational study on the epidemiology of multiresistant Enterobacteriaceae was conducted in the neurology and neurosurgery wards of a university hospital to determine the impact of hospital hygiene measures and an additional temporary restrictive antibiotic agent policy on the sudden rise in incidence of these bacteria. The incidence and prevalence of patients with multiresistant Enterobacteriaceae were assessed, and patient isolates were typed phenotypically and by random amplified polymorphic DNA analysis. All hospital hygiene measures implemented were recorded, and the influence of the restrictive policy on antibiotic use was analyzed. This policy consisted of a prior authorization requirement and the withdrawal of all antibiotics with a possible selective pressure on multiresistant strains (gentamicin, tobramycin, quinolones, cotrimoxazole, broad-spectrum penicillins, and cephalosporins). This ban left only carbapenems and amikacin for treatment. Typing showed that 17 of the 61 (28%) patients involved were infected or colonized with a single multiresistant strain of Klebsiella oxytoca, for which an environmental source was identified. The isolates recovered from the other patients comprised eight different species, and subsequent genotyping yielded a great variety of strains. The increased incidence could not be controlled with hospital hygiene measures alone. Only after implementation of the restrictive antibiotic policy did the epidemic strain vanish and the endemic incidence of multiresistant Enterobacteriaceae decrease to <50% of the level before intervention. In the years since, the incidence has remained at this low level, and the antibiotic costs have decreased to a level lower than before intervention.

The frequency of isolation of pathogens that cause different types of infections is an important guide for empiric therapy. As part of the SENTRY Antimicrobial Surveillance Program, the frequency of isolation of different bacterial species from bloodstream, nosocomial pneumonia, skin and soft tissue, and urinary tract infections occurring in European patients was determined. A total of 15,704 isolates were collected in 1997 and 1998 from 24 university hospitals in 14 European countries: 9,194 from bloodstream, 2,052 from nosocomial pneumonia, 2,320 from skin and soft tissue, and 2,138 from urinary tract infections. More than 95% of all bacterial infections were caused by only 15 different genera. Staphylococcus spp. and Escherichia spp, accounted for more than 50% of the infectious isolates, with the exception of those obtained from cases of nosocomial pneumonia. In the latter type of infection, isolates belonging to these two genera were responsible for 30% of the infections. An analysis at the individual species level showed that Escherichia coli caused a large proportion of bloodstream and urinary tract infections (20.8% and 49.3% of isolates, respectively). Staphylococcus aureus was the main causative species for nosocomial pneumonia and skin and soft tissue infections (21.5% and 37.4% of isolates, respectively). In addition, Pseudomonas aeruginosa played an important role in all types of infection analyzed.

During a five year surveillance program of patients with communicable diseases nursed in isolation, we gathered information on 2880 patients who were nursed in isolation for 28 145 days, from January 1994 to December 1998. The mean number of patients nursed in isolation was 575.4 (range, 427-709) per year. On average 2.4% of patients admitted yearly to the University Medical Center (UMC) were nursed in isolation. The mean number of days nursed in isolation was 9.8 days per patient.1996 was a peak year in isolations due to outbreaks of gentamicin-resistant enterobacteriaceae (GRB) and methicillin resistant Staphylococcus aureus (MRSA). The main reasons for requiring isolation were: GRB, MRSA (proven and suspected cases), Clostridium difficile, viral infections and Mycobacterium tuberculosis. Registration of quantitative data on nursing patients in isolation, as presented in this paper, makes it possible to gain insight into the type and number of isolation indications, the required isolation room capacity on different wards, the workload of healthcare workers resulting from isolation and the trends in incidence of communicable diseases., (Copyright 2001 The Hospital Infection Society.)

Nosocomial isolates of Pseudomonas aeruginosa and Acinetobacter spp. exhibit high rates of resistance to antibiotics and are often multidrug resistant. In a previous study (D. Milatovic, A. Fluit, S. Brisse, J. Verhoef, and F. J. Schmitz, Antimicrob. Agents Chemother. 44:1102-1107, 2000), isolates of these species that were resistant to sitafloxacin, a new advanced-generation fluoroquinolone with a high potency and a broad spectrum of antimicrobial activity, were found in high proportion in 23 European hospitals. Here, we investigate the clonal diversity of the 155 P. aeruginosa and 145 Acinetobacter spp. sitafloxacin-resistant isolates from that study by automated ribotyping. Numerous ribogroups (sets of isolates with indistinguishable ribotypes) were found among isolates of P. aeruginosa (n = 34) and Acinetobacter spp. (n = 16), but the majority of the isolates belonged to a limited number of major ribogroups. Sitafloxacin-resistant isolates (MICs > 2 mg/liter, used as a provisional breakpoint) showed increased concomitant resistance to piperacillin, piperacillin-tazobactam, ceftriaxone, ceftazidime, amikacin, gentamicin, and imipenem. The major ribogroups were repeatedly found in isolates from several European hospitals; these isolates showed higher levels of resistance to gentamicin and imipenem, and some of them appeared to correspond to previously described multidrug-resistant international clones of P. aeruginosa (serotype O:12) and Acinetobacter baumannii (clones I and II). Automated ribotyping, when used in combination with more discriminatory typing methods, may be a convenient library typing system for monitoring future epidemiological dynamics of geographically widespread multidrug-resistant bacterial clones.

We describe and compare the organization of infection control and some infection control practices in 10 hospitals in seven different European countries. Great differences were observed. By evaluating infection control and hygiene practices in different European centers, areas of prime importance for the development of a European infection control standard may be defined.

The cultures of two patients of the Surgical Intensive Care Unit (IC) of the Medical Centre of Utrecht University were found positive for methicillin-resistant Staphylococcus aureus (MRSA). A male nurse turned out to be the source, 4 months after his return from working in an English hospital. Cultures were, by mistake, not taken directly on arrival from abroad. Pulsed-field gel electrophoresis proved MRSA strains from both source and the 2 patients to be identical to a strain which was epidemic in Great Britain but had never occurred in the Netherlands. The IC has meanwhile been closed; at source investigation, 14 other patients and six staff members were found MRSA-positive. The policy in the hospital is to screen health care workers for MRSA carriership on return from an hospital abroad. The success of the policy depends strongly on the cooperation of health care workers in this matter.

The SENTRY Antimicrobial Surveillance Program was established to monitor the occurrence and antimicrobial susceptibility of bacterial pathogens via an international network of sentinel hospitals. Twenty European hospitals referred a total of 887 urinary tract infection (UTI) isolates to the European SENTRY reference laboratory during the period October-December 1997. Ninety percent of the referred species were represented by Escherichia coli (52%), Enterococcus spp. (12%), Klebsiella spp. (7%), Proteus spp. (7%), Pseudomonas aeruginosa (7%), and Enterobacter spp. (5%). The susceptibility of E. coli isolates to penicillins was less than 60%, while almost all of the isolates were susceptible to piperacillin/tazobactam (98% susceptibility), cephalosporins (98%), and carbapenems (100%). Amikacin was the best aminoglycoside (99.8% susceptibility). The susceptibility to quinolones was only 88-89%, with highest levels of resistance observed for isolates from Portugal, Italy, England, The Netherlands, and some centers in France, Spain, and Poland. The susceptibility of Klebsiella spp. to the newer generations of cephalosporins was 82-95% and to the carbapenems 100%. Amikacin was again the best aminoglycoside (94% susceptibility). The susceptibility of Enterobacter spp. to any beta-lactam antibiotic was poor, except for the carbapenems (100% susceptibility) and cefepime (90% susceptibility), while the susceptibility to aminoglycosides was 80-89%. Proteus spp. showed complete susceptibility to cefepime, ceftriaxone, the carbapenems, and piperacillin/tazobactam, while the susceptibility of P. aeruginosa isolates was poor, with best results for the carbapenems (susceptibility 89%), piperacillin/tazobactam (susceptibility 84%), and amikacin and ticarcillin (susceptibility to both 80%). Enterococcus spp. showed the highest susceptibility to vancomycin (98%), teicoplanin (98%), and ampicillin (94%).

The in-vitro activities of gatifloxacin, trovafloxacin, levofloxacin, sparfloxacin, ofloxacin, and ciprofloxacin were tested against 9,682 clinical bacterial isolates from 20 European university hospitals participating in the European SENTRY surveillance programme. Gatifloxacin and trovafloxacin exhibited the highest activities against gram-positive cocci, while levofloxacin, ofloxacin, ciprofloxacin, and gatifloxacin were the most active against Enterobacteriaceae. Ciprofloxacin and levofloxacin showed the highest antimicrobial activities against Pseudomonas spp., while gatifloxacin and trovafloxacin were the most active against Acinetobacter spp. and Stenotrophomonas maltophilia. All Haemophilus spp. and Moraxella catarrhalis isolates were fully susceptible to all quinolones tested. Overall, the new quinolones, showed improved activity against gram-positive cocci and gram-negative non-fermenters while retaining their broad-spectrum activity against gram-negative bacilli.

Over a period of three years the incidence of methicillin resistant Staphylococcus aureus (MRSA) isolates in 11 hospitals in the greater Düsseldorf area was observed. From a total of 7,814 S. aureus isolates, 489 (6.3%) were methicillin resistant. From 198 different patients, MRSA first isolates and 291 second isolates could be cultured. Methicillin resistance among all S. aureus isolates from 11 hospitals in the greater Düsseldorf area, ranged from 0.5 to 7.8% dependant on the size of the hospital. The highest incidence (7.8%) was found in a 1,500 bed hospital and the lowest incidence in a smaller 200 bed hospital (0.5%). With respect to the distribution among clinical departments the highest incidence of MRSA isolates was found on intensive care units and surgical wards, 25.5% and 13.0% respectively. The commonest specimen from which the MRSA isolates were cultured were respiratory secretions (17.6%) followed by central venous catheter tips (12.8%). In terms of the drug resistance pattern: all isolates were resistant to the aminoglycosides and gyrase inhibitors, whereas between 80% and 90% were sensitive to fusidic acid, chloramphenicol and pyrimethamine-sulfamethoxazole. All the strains were sensitive to the glycopeptide antibiotics, vancomycin and teicoplanin. Strain typing of 181 available first isolates (from a total of 198 first isolates) by PFGE and phage lysotyping produced identical results in more than 90% of all cases. Twenty-eight different MRSA strain types were identified by PFGE and in total 23 lysotypes could be determined. During the period of investigation an increased incidence of MRSA on an intensive care unit was observed, in which a total of 204 MRSA (42% of the total number) were isolated. The strain typing using both methods showed that on that ICU eight different MRSA types were involved in this outbreak. A hygiene plan was implemented on the unit with considerable success in reducing the incidence and spread of MRSA.

Prospective surveillance of hospital-acquired infections was undertaken in the geriatric ward of the University Hospital, Utrecht, the Netherlands. The medical records of 300 patients were studied for the presence of nosocomial infections using the criteria defined by the Centers for Disease Control (CDC), Atlanta, Georgia, USA. Data were collected from patients with and without infection, which allowed for the analysis of risk factors for nosocomial infection. In 100 out of 300 patients (33.3%), a total of 126 infections was diagnosed. The incidence of nosocomial infections was 16.9 per 1000 days of stay in the hospital. The mean length of stay of patients with infection was 39 days, while that of patients without infection was 17.8 days. Infections developed after an average stay of 13.3 days in the hospital. Patients with infections were 2.6 years older than patients without infections (P = 0.005). Dehydration was shown to be a major risk factor for infection (RR = 2.1, 95% CI: 1.4-3.2). Of the infections, 58.7% were urinary tract infections (UTIs, asymptomatic and symptomatic). The most important risk factor for an asymptomatic UTI was an indwelling urinary catheter (RR = 7.3, 95% CI: 3.1-17.1). The duration of use of the indwelling urinary catheter was of significant influence in the development of a UTI. Seventy percent of the patients with an asymptomatic UTI were treated with antibiotics. Infections of the gastrointestinal tract accounted for 19.8% of all nosocomial infections. The majority of these infections were due to an outbreak of Clostridium difficile. In conclusion, the length of stay may be prolonged by a nosocomial infection. In this study, the main risk factors for developing a nosocomial infection were age, dehydration and the presence of an urinary catheter. Our observations showed that age is a predisposing factor for nosocomial infection and that the risk increases with each year, even for geriatric patients.

Background: Most studies of the cause of sepsis syndrome focus on patients hospitalized in intensive care units. In this study, we analyzed the incidence, cause, and outcome of the sepsis syndrome in all hospitalized patients., Methods: Clinical and microbiologic data were obtained for 382 patients (5.6% of all patients admitted) from whom blood was drawn for culture., Results: The incidence of the sepsis syndrome was 13.6 per 1000 patients admitted (1.06 per 1000 hospital days), while the incidence of septic shock was 4.6 per 1000. The respiratory tract was the predominant infection site. Of all patients with sepsis syndrome, 38% (n = 35) had positive blood cultures. More than half of these cultures (13 [57%]) were caused by gram-positive microorganisms (excluding patients receiving selective decontamination of the digestive tract and those with intravascular device-related bacteremias). The mortality for patients with sepsis syndrome without shock was 28% (17/61), while for patients with septic shock, it was 55% (17/31). Patients with cardiovascular diseases had a significantly (P < .005) greater risk of dying during a sepsis syndrome episode than patients with other predisposing factors. Multivariate analysis of factors influencing outcome identified the development of shock and an immunocompromised state as being significantly associated with outcome in patients with sepsis syndrome., Conclusions: Patients fulfilling the criteria for the sepsis syndrome are at great risk of developing septic shock or multiple-organ failure and subsequently dying. In our hospital, the majority of bacteremic episodes were associated with gram-positive microorganisms.

Between 1986 and 1989 a single strain of a methicillin- and multiply-resistant Staphylococcus aureus caused three distinct outbreaks at Utrecht University Hospital, involving 11, 19 and 32 patients, respectively. In all three episodes, members of staff were screened for MRSA carriage, and 58 persons were found to have positive nose cultures. In each outbreak it became necessary to isolate colonized and infected patients on a separate isolation ward. Staff carriers were also treated. Over the 18 months since the last outbreak, no new acquisitions of this epidemic MRSA strain have occurred. Between 1986 and 1989, the strain which caused the three outbreaks was not the only MRSA strain which was introduced into the hospital. Six other strains, which differed from the epidemic strain as shown by phage typing and antimicrobial susceptibility pattern, were found in single patients. The experience at Utrecht University Hospital illustrates the need for strict measures to eradicate epidemic strains of MRSA as well as the differences in "epidemicity" among various strains of MRSA.

Between December 1988 and March 1989 twelve patients in the Utrecht University Hospital developed an infection with a methicillin-resistant Staphylococcus aureus (MRSA). Twenty other patients and 39 personnel members became colonized with the same MRSA strain. In spite of early isolation measures, progression of this epidemic was probably caused by the extreme degree of contagiousness of the first patient, who had a drug-induced allergic skin eruption. It seems likely that spread occurred via personnel and via a computer tomographic scanner. To contain the epidemic it was necessary to institute a special isolation ward with dedicated personnel. Although several MRSA strains have been introduced in the University Hospital since 1986, the strain we describe here is the only one which spread epidemically.

Colonization and infection with an endemic multiresistant strain of Acinetobacter calcoaceticus variety anitratus had been observed in the surgical intensive care unit of a university hospital since 1982. An outbreak of infection with this endemic, multiresistant Acinetobacter anitratus strain occurred between January and September, 1984. After initial attempts at identification of environmental reservoirs had been unsuccessful, risk factors for the acquisition of Acinetobacter anitratus were investigated by comparing the epidemiological characteristics of patients who became colonized or infected with those of control patients without colonization. The results of this case-control study and of the ensuing specific cultures indicated that ventilators in use in the unit were the reservoirs of Acinetobacter anitratus, resulting in frequent nosocomial respiratory tract infections. After modification of the mechanical ventilators, colonization and infection rates with Acinetobacter anitratus decreased. Since January 1985, no new cases of colonization or infection with this endemic strain of Acinetobacter anitratus have been recorded.

In a prospective randomized study to determine whether prevention of colonization of Gram-negative bacteria results in prevention of Gram-negative bacterial infections, 96 intensive care patients were randomly allocated into a control group and a study group. The study group received oral nonabsorbable antimicrobial agents (i.e., tobramycin, amphotericin B, and polymyxin E) in addition to parenteral antibiotics. Colonization with Gram-negative microorganisms in the oropharynx, and respiratory and digestive tracts increased in the control group during their stay, while the study group did not tend to colonize with Gram-negative bacteria. In the control group, 107 nosocomial infections were diagnosed, vs. 42 nosocomial infections in the study group. Nosocomial infections caused by Gram-negative bacteria were significantly less frequent in the study group. Mortality due to an acquired infection was significantly less frequent in the study group. We conclude that colonization, infection, and subsequent mortality by nosocomial Gram-negative bacteria can be prevented by a regime of topically applied nonabsorbable antibiotics.

Nosocomial infections are a major problem in intensive care patients. Thirty-nine patients, requiring intensive care for 5 days or more (mean 15.8 days) were prospectively investigated, to determine the relation between colonisation and nosocomial infection. Thrice weekly, cultures from the oropharynx, respiratory and digestive tract were obtained. Colonization with aerobic gram-negative microorganisms of the oropharynx, respiratory and digestive tract significantly increased during the stay in the Intensive Care Unit. In 29 patients (74%) 78 nosocomial infections were diagnosed. The most frequent nosocomial infections were pneumonia (26 patients, 66.6%), catheter-related bacteraemia (11 patients, 28.2%), and wound infections (7 patients, 17.9%). In 59 instances (75.6%), colonization with the same potential pathogenic microorganism preceded the nosocomial infection. The overall mortality was 25.6% (10 patients), bacteraemia with aerobic gram-negative microorganisms being the cause of death in 7 patients.

Staphylococcus epidermidis are the most common agents of prosthetic valve endocarditis (PVE). S. epidermidis isolated from the blood stream of patients with PVE are almost invariably multiple resistant to antibiotics. Antibiotic treatment alone gives unsatisfactory results and carries a mortality rate of 70-80%. That is why early surgical treatment is recommended. S. epidermidis is a less common cause of endocarditis in non-surgical patients, accounting for approximately 5% of the cases, which are mostly patients with pre-existent valvular heart disease. Generally, isolates from the latter patients are sensitive to most antibiotics, and the mortality rate is considerably lower. Recently coagulase-negative staphylococci have emerged as causative agents of septicaemia in patients hospitalized in intensive care units. Especially premature infants of very low-birth weight (less than 1500 g) receiving parenteral nutrition appear to carry a high risk of acquiring this kind of septicaemia. Although the staphylococci isolated from the blood of these patients are the same as in patients with PVE, generally multiple resistant to antibiotics, prognosis is far better than in cases of PVE. In our study carried out in a neonatal intensive care unit, two risk factors for coagulase-negative staphylococcal septicaemia were identified. First, nearly 20% of parenteral nutrition fluids used in the unit were found to be contaminated with coagulase-negative staphylococci, and a significant association was established between septicaemia and the infusion of contaminated fluids. Moreover, opsonization of staphylococci in infant serum proved to be severely deficient. Since host defence to staphylococci is dependent on optimal opsonization of these microorganisms, this defence may be severely compromised in the premature neonate.(ABSTRACT TRUNCATED AT 250 WORDS)