Transmission of herpes simplex virus type 1 infection in an intensive care unit.
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Biomedical subjects
Publications and source records attributed to M A Pfaller.
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BACKGROUND: Effective hand-washing can prevent nosocomial infections, particularly in high-risk areas of the hospital. There are few clinical studies of the efficacy of specific hand-cleansing agents in preventing the transmission of pathogens from health care workers to patients. METHODS: For eight months, we conducted a prospective multiple-crossover trial involving 1894 adult patients in three intensive care units (ICUs). In a given month, the ICU used a hand-washing system involving either chlorhexidine, a broad-spectrum antimicrobial agent, or 60 percent isopropyl alcohol with the optional use of a nonmedicated soap; in alternate months the other system was used. Rates of nosocomial infection and hand-washing compliance were monitored prospectively. RESULTS: When chlorhexidine was used, there were 152 nosocomial infections, as compared with 202 when the combination of alcohol and soap was used (adjusted incidence-density ratio [IDR], 0.73; 95 percent confidence interval, 0.59 to 0.90). The largest reduction with chlorhexidine was in gastrointestinal infections (IDR, 0.19; 95 percent confidence interval, 0.05 to 0.64). When chlorhexidine was available, the rates of nosocomial infection declined in each of the ICUs, and health care workers washed their hands more often than when alcohol and soap were used (relative risk, 1.28; 95 percent confidence interval, 1.02 to 1.60). The total volume of alcohol and soap used was 46 percent that of chlorhexidine (P less than 0.001). CONCLUSIONS: A hand-disinfection system using an antimicrobial agent (chlorhexidine) reduces the rate of nosocomial infections more effectively than one using alcohol and soap. The improvement may be explained at least in part by better compliance with hand-washing instructions when chlorhexidine was used.
The authors performed a matched historic cohort study to determine the attributable mortality and risk factors for nosocomial pneumonia in bone marrow transplant (BMT) recipients. All patients with nosocomial pneumonia at a university tertiary care center were identified by a prospective surveillance system between 1980 and 1988. Control patients were selected from the population of BMT patients. The crude mortality for 55 patients with nosocomial pneumonia was 74.5% (95% confidence interval [CI95], 63% to 86%). The excess or attributable mortality was 61.8% (CI95, 43.7% to 80%). Aspergillus species represented the most frequent etiologic agent in this series, causing 20 of the 55 (36%) episodes. The attributable mortality of Aspergillus species pneumonia alone was 85% (CI95, 58.6% to 100%). For death in the hospital, the risk ratio for all 55 case patients relative to control patients was 9.5 (CI95, 4.1 to 22.1). To evaluate several risk factors simultaneously, a multiple logistic regression analysis using a conditional likelihood method was performed. A mathematical model with three variables best predicted nosocomial pneumonia in our patients: the occurrence of other nosocomial infections before the diagnosis of pneumonia, allogeneic BMT, and the use of methotrexate. The presence of other nosocomial infections before the diagnosis of pneumonia remained a significant independent risk factor, with an odds ratio of 13.27 (CI95, 2.51 to 70.2) after adjustment for the use of methotrexate and allogeneic BMT. Most importantly, effective methods for preventing nosocomial pneumonias in BMT recipients will have an enormous effect on crude mortality.
The availability of an epidemiologic typing system for Candida species that is sensitive, rapid, inexpensive, and easy to perform would clearly be an advantage to the mycologist, microbiologist, and epidemiologist in the ongoing struggle to understand the epidemiology and pathogenesis of candidiasis. This is particularly true given the increasing prominence of organisms such as C. albicans and C. tropicalis which are ubiquitous members of the normal flora yet are also important causes of nosocomial bloodstream infection. Unfortunately, the ideal epidemiologic typing system does not yet exist. Current data suggest that the molecular typing methods of restriction endonuclease digestion of genomic DNA with ethidium bromide staining (DEtBr typing) and electrophoretic karyotyping using pulsed-field electrophoresis offer rapid, simple, and sensitive means of discriminating strains of Candida species. These methods appear at present to be the most practical typing methods for both large- and small-scale epidemiologic studies. Other typing methods using specific DNA probes provide a powerful means of identifying strains and will undoubtedly be applied more broadly in the future. Thus far, studies employing molecular typing methods have documented that (1) most patients are colonized by one strain of Candida species, (2) isolates of Candida species recovered from blood or deep tissue sites are generally identical to those obtained from colonization sites before infection developed, and (3) nosocomial transmission of a single strain of C. albicans may occur, particularly in an intensive care unit setting. Given the limitations of the available typing methods and the complex nature of the patients at risk for candidiasis, both the epidemiologist and laboratory scientist must use these methods with clear epidemiologic objectives in mind. Whenever possible, all organisms to be typed should be typed by the same person on the same day, and typing should always include unrelated as well as epidemiologically related isolates. Additional studies, based upon sound epidemiologic principles, will be necessary to clarify the role of the various molecular typing methods as epidemiologic markers of Candida species and to further our understanding of the epidemiology and pathogenesis of candidiasis.
A total of 1,303 sera from 202 patients at risk for disseminated candidiasis were analyzed for the presence of Candida antigen using a commercially available latex agglutination test (Cand-Tec). Twenty-three patients had disseminated candidiasis documented by positive blood cultures, deep biopsy culture and histopathology or autopsy. Six patients had transient candidemia, 15 patients had candiduria, 62 patients were not colonized yet treated empirically with amphotericin B, and 46 patients were not colonized and not treated with amphotericin B. The sensitivity and specificity of the Candida antigen test for the diagnosis of disseminated candidiasis was 87% and 36% (threshold titer of greater than or equal to 1:2), 70% and 60% (greater than or equal to 1:4), and 30% and 85% (greater than or equal to 1:8), respectively. In contrast to previous studies we were unable to demonstrate a prognostic role for the Candida antigen test in patients with documented disseminated candidiasis. The lack of sensitivity and specificity of the Cand-Tec Candida antigen test precludes its use in the diagnosis of disseminated candidiasis.
The laboratory diagnosis of candidiasis continues to be problematic; however, there have been several advances in the past decade which promise to enhance our ability to identify patients at high risk for infection and/or to document invasive candidiasis in critically ill and immunocompromised patients. The introduction of commercially available biphasic blood culture medium and subsequently the lysis-centrifugation procedure has markedly improved the ability of laboratories to detect fungemia. Although serologic methods have not been very successful in diagnosing candidiasis in immunocompromised patients, several antigen detection methods are now under investigation. In addition, detection of fungal metabolites such as D-arabinitol remains promising. Finally, application of the techniques of molecular biology for typing and detection of fungal pathogens has expanded our understanding of candidal infections and may offer the most sensitive and specific means of diagnosing invasive candidiasis.
In a collaborative study involving five medical centers, 6% of 2,440 consecutive isolates of Enterobacteriaceae were resistant to cefoperazone; resistance to cefoperazone was reduced to < 1% by the addition of sulbactam. Susceptibility to cefoperazone and cefoperazone-sulbactam was accurately predicted by disk diffusion tests. Resistance to cefoperazone, however, was not as reliably detected by disk tests and results of dilution tests were not always consistent. The prevalence of resistance to cefoperazone and/or the ability to detect resistance had a significant influence on very major error rates for individual laboratories.
Staphylococcus aureus isolates (n = 1201) from 20 centers in Europe, the USA and Brazil were evaluated for the presence of epidemiologic markers. Plasmid typing and restriction endonuclease analysis of plasmid DNA confirmed the presence of an apparently identical plasmid in 13% of clinical isolates. The plasmid was recovered from all 20 hospitals studied, with an overall frequency of greater than 10% on each of the three continents. Since relatively few staphylococcal plasmids may be shared by epidemiologically unrelated strains, there are inherent limitations to this otherwise useful technique. Additionally, these data demonstrate the importance of including unrelated strains of Staphylococcus aureus from the local region as controls when molecular typing methods are performed.
Piperacillin combined with tazobactam was tested at both a fixed ratio (8:1) and fixed tazobactam concentration (4 micrograms/ml) against 2,685 consecutively isolated gram-negative bacilli and 56 highly piperacillin-resistant isolates. Tazobactam significantly enhanced the spectrum of piperacillin activity. Overall, at a concentration of 16 micrograms/ml piperacillin alone inhibited 78.8% of the Enterobacteriaceae isolates compared to inhibition of 92.7% and 95.5% by the 8:1 ratio and fixed (4 micrograms/ml) tazobactam combinations, respectively. In MIC tests the two combination options performed comparably against both routine and highly piperacillin-resistant isolates. Synergistic inhibition was observed for comparable numbers of isolates with the two combination options, the most marked effect being seen in the more highly piperacillin-resistant isolates. Both testing options are supported by the available human pharmacokinetic data; however the 8:1 ratio of piperacillin to tazobactam may be preferable given that the clinical formulation contains the two compounds in an 8:1 ratio and this ratio is maintained in vivo.
The frequency of spontaneously occurring mutants resistant to 0.5, 1, 2, 4 and 8 micrograms of temafloxacin or ciprofloxacin per milliliter was documented with four Staphylococcus aureus and four Staphylococcus epidermidis strains. Resistant mutants were recovered at two- to four-fold the MIC of either drug, and they displayed cross-resistance to other fluoroquinolones. Resistance to temafloxacin occurred at frequencies lower than those observed with equal concentrations of ciprofloxacin. Resistance to greater than four-fold the MIC of either drug was not detected (frequencies less than 10(-10).
Episodes of septicaemia due to coagulase-negative staphylococci (CNS) were more frequent in a level III than in a level II neonatal unit in Stockholm, Sweden. Colonization with CNS during the first 2 weeks of life was investigated in 10 infants from each unit. As the use of antibiotics differed between the two units, the aim was to correlate colonization and antimicrobial resistance patterns to antibiotic usage. Antimicrobial susceptibility of CNS to isoxazolylpenicillins, co-trimoxazole, erythromycin, clindamycin, chloramphenicol and gentamicin was determined. Selected isolates were typed with restriction endonuclease analysis of plasmid DNA and of genomic DNA. Infants were frequently colonized with multiple strains and species of CNS, and transmission of strains from patient to patient occurred within the unit. Qualitative and quantitative differences in antibiotic use were not correlated with colonization. The prevalence of resistant isolates, mostly of Staphylococcus haemolyticus, was higher in the level II unit with lower use of antibiotics. Staphylococcus epidermidis, which is generally more virulent, prevailed in the level III unit, where there were more severely ill children and invasive procedures were more frequently performed.
Lomefloxacin and meropenem were tested in a multilaboratory study to establish susceptibility testing interpretive criteria and quality control (QC) guidelines for Haemophilus influenzae using Haemophilus test medium (HTM). Interpretive criteria were established by using triplicate testing of 102 representative H. influenzae strains. Only a susceptible category was proposed for lomefloxacin (greater than or equal to 22 mm and less than or equal to 2 micrograms/ml) and meropenem (greater than or equal to 13 mm and less than or equal to 4 micrograms/ml) due to the lack of resistant isolates. QC range for H. Influenzae ATCC 49247 were established using multiple HTM agar and broth base lots, three disk lots for each drug, and a number of test replicates consistent with the National Committee for Clinical Laboratory Standards M23-T guideline.
Cefdinir, a new oral cephalosporin, was compared to cefaclor, cefadroxil, cefixime, and cefuroxime against greater than 5000 recent aerobic clinical isolates. This multicenter study revealed broad-spectrum cefdinir activity against all Enterobacteriaceae (MIC50s, 0.06-2 micrograms/ml) except Enterobacter cloacae, Morganella morganii, Proteus vulgaris, and Serratia marcescens (MIC50s, greater than or equal to 4 micrograms/ml). Oxacillin-susceptible staphylococci (MIC90s, 0.5-2 micrograms/ml), beta-hemolytic Streptococcus group B (MIC90, 0.06 micrograms/ml), and Acinetobacter lwoffii were also susceptible to cefdinir. The activity of cefdinir was similar to that of cefixime and cefuroxime against Gram-negative organisms and superior to all tested oral cephems when tested against Gram-positive cocci. None of the cephalosporins were active against oxacillin-resistant Staphylococcus spp., enterococci, Pseudomonas spp., or Xanthomonas maltophilia. MIC quality control range guidelines were established for the strains recommended by the National Committee for Clinical Laboratory Standards documents.
An outbreak of candidemia involving five infants receiving total parenteral nutrition in the neonatal intensive care unit was investigated. Cultures of the intravenous fluids demonstrated that the retrograde medication syringe fluids were significantly more likely to be contaminated with Candida than were other fluids being administered to the infants (p less than 0.001). Candidemia was significantly associated with total parenteral nutrition (p = 0.04) and retrograde medication administration (p = 0.02). A survey of nursing practice found that reuse of the retrograde syringes was the most likely cause of contamination. Molecular typing showed that the strains of Candida albicans that were isolated from the bloodstream were also found in the retrograde syringes and that at least three strains of C. albicans and one strain each of Candida tropicalis and Candida parapsilosis were involved. In vitro growth curves demonstrated that Candida species had a selective growth advantage versus bacteria in the total parenteral nutrition fluid. An in vitro simulation of the retrograde medication administration system suggested that the outbreak probably developed after the frequency of changing intravenous tubing was decreased from every 24 hours to every 72 hours. The outbreak was terminated by using syringes only once and resuming intravenous tubing changes every 24 hours. Retrograde medication administration in association with total parenteral nutrition may increase the risk of Candida line infection.
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OBJECTIVE: To define the source of invasive coagulase-negative staphylococci (CNS) and the epidemiology of strain variation in immunocompromised patients. DESIGN: Weekly microbial surveillance cultures were obtained from the nares, throat, skin, rectum, and urine. Plasmid pattern analysis was performed on all coagulase-negative staphylococci isolated from blood cultures and on selected strains from the surveillance sites. SETTING: A 902-bed, university-owned, tertiary-care referral hospital. PARTICIPANTS: Forty-four patients on the bone marrow transplant or hematologic malignancy services. RESULTS: Plasmid pattern analysis was performed on 340 surveillance isolates (median = 7 per patient) and 201 bloodstream isolates (median = 3 per patient). Patients were colonized with numerous unique strains (median = 5 per patient) of coagulase-negative staphylococci. The 44 patients had 108 episodes of positive blood cultures, 20 of which were preceded by colonization with the same strain. Isolation of the matching strain from surveillance cultures preceded the positive blood culture by 1 to 8 days in 9 episodes and 18 to 389 days in 11 episodes. The matching strain was isolated from the skin in only 6 (30%) of those episodes and from mucosal sites in 70%. Of the 108 episodes of positive blood cultures, 21 were identified as nosocomial bloodstream infections. Four of the 21 nosocomial bloodstream infections were preceded by colonization with the same strain. In all 4 episodes, the infecting strain was cultured from the nares before the blood cultures were obtained. CONCLUSIONS: Our results suggest that mucous membranes might be sources for strains of CNS causing bacteremia.
Despite the increasing importance of nosocomial fungal infections, very little is known of the epidemiology, mode of transmission, or pathogenesis of infections due to fungal pathogens. Recently, a number of potentially useful epidemiological typing systems have been employed for identification of strains within species of Candida and other fungi. Epidemiological studies employing either DNA-based or protein-based typing methods have provided some interesting insights into the epidemiology of nosocomial fungal infections, particularly nosocomial candidiasis. Careful epidemiological studies employing selected typing methods are essential to the rational development of effective measures for prevention and control of nosocomial infections caused by opportunistic fungal pathogens.