The epidemiology of mupirocin resistance among methicillin-resistant Staphylococcus aureus at a Veterans' Affairs hospital.

OBJECTIVE: To describe the clinical and molecular epidemiology of mupirocin-resistant (MR) and mupirocin-susceptible (MS) methicillin-resistant Staphylococcus aureus (MRSA) at a Veterans' Affairs hospital and to assess risk factors associated with the acquisition of MR MRSA. DESIGN: All clinical MRSA isolates for the period October 1990 through March 1995 underwent susceptibility testing to mupirocin. Mupirocin resistance trends were measured, and MS MRSA and MR MRSA isolates underwent typing by pulsed-field gel electrophoresis (PFGE). A retrospective case-control study was conducted to evaluate risk factors for having MR versus MS MRSA. SETTING: The James H. Quillen Veterans' Affairs Medical Center in Mountain Home, Tennessee, included a 324-bed acute-care hospital, a 120-bed nursing home, and a 525-bed domiciliary. Colonizations and infections with MRSA were endemic, and mupirocin ointment was commonly used. PATIENTS: Inpatients and outpatients at the facility. RESULTS: MS MRSA was recovered from 506 patients and MR MRSA from 126. Among MR MRSA isolates, 58% showed low-level mupirocin resistance (minimum inhibitory concentration [MIC] > or = 4 to 256 microg/mL), and 42% showed high-level mupirocin resistance (MIC > or = 512 microg/mL). A significant increase (P=.002) in the number of high-level MR isolates occurred during the 1993 to 1995 period. A case-control study showed that presence of a decubitus ulcer correlated with high-level resistant isolates (P<.05). The distribution of PFGE patterns did not differ for MR and MS MRSA CONCLUSIONS: Use of mupirocin ointment in a program aimed at managing endemic MRSA infection or colonization resulted in a significant increase in the recovery of high-level MR MRSA isolates. These isolates appeared to emerge from our existing MRSA pool. A case-control study provided few clues concerning patients likely to harbor MR MRSA. We confirmed the position that the extended use of mupirocin ointment should be avoided in settings where MRSA is endemic.

Methicillin-resistant Staphylococcus aureus outbreak: a consensus panel's definition and management guidelines.

OBJECTIVE: To provide medical personnel with a definition of an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) and guidelines for managing potential outbreaks. PARTICIPANTS: Eighteen panel members were chosen from different specialties, types of institutions, and geographic regions. Representatives from the American Society of Consultant Pharmacists, the American Society of Health-Systems Pharmacists, the Society for Healthcare Epidemiology of America, and the National Association of Directors of Nursing Administration participated. CONSENSUS PROCESS: In preparation for the conference, panel members reviewed the literature and wrote abstracts outlining their personal opinions on the core issues, which were circulated to all participants. During a weekend conference, the panel summarized the reviewed literature, defined an MRSA outbreak, and developed management guidelines. EVIDENCE: Published literature, clinical experience, and expert opinion concerning the emergence and subsequent management of MRSA cases in health care institutions. RESULTS: An outbreak of MRSA was defined as either an increase in the rate of MRSA cases or a clustering of new cases due to the transmission of a single microbial strain in the health care institution. An increased rate of cases can be defined statistically or experientially and includes both infected and colonized patients. A potential outbreak should trigger stepwise, multidisciplinary actions consisting of basic epidemiologic procedures (phase I) to form an initial epidemiologic hypothesis of an outbreak (phase II) followed by a standard epidemiologic workup (phase III) and microbiologic studies (phase IV) to confirm the hypothesis. Mupirocin calcium treatments should be considered to decolonize health care workers during the fourth phase, even before typing is completed. CONCLUSIONS: Until studies can be conducted to delineate the effectiveness of different recommendations, the proposed guidelines may provide a useful starting point that can be adapted to meet an individual institution's specific needs.

Microcomputers in hospital epidemiology.

Computers can store, manage, and analyze large quantities of data. Thus, computers are an ideal tool for the modern practice of infection control. This article provides practical information for infection control personnel who must choose or upgrade a computer system.

A cloud adult: the Staphylococcus aureus-virus interaction revisited.

BACKGROUND: Nasal carriage of Staphylococcus aureus is common among health care workers, but outbreaks caused by such carriers are relatively uncommon. We previously reported outbreaks of S. aureus skin infections that affected newborn infants and were attributed to an S. aureus nasal carrier who had had an associated upper respiratory tract infection (UR) during the outbreak period. OBJECTIVE: To investigate the contribution of a nasal methicillin-resistant S. aureus (MRSA) carrier (physician 4) who contracted a URI to an outbreak of MRSA infections that involved 8 of 43 patients in a surgical intensive care unit during a 3-week period. DESIGN: An epidemiologic study of an outbreak of MRSA infections and a quantitative investigation of airborne dispersal of S. aureus associated with an experimentally induced rhinoviral infection. SETTING: A university hospital. PARTICIPANTS: 43 patients in a surgical intensive care unit and 1 physician. MEASUREMENTS: Molecular typing was done, and risk factors for MRSA colonization were analyzed. Agar settle plates and volumeric air cultures were used to evaluate the airborne dispersal of S. aureus by physician 4 before and after a rhinoviral infection and with or without a surgical mask. RESULTS: A search for nasal carriers of MRSA identified a single physician (physician 4); molecular typing showed that the MRSA strain from physician 4 and those from the patients were identical. Multivariate logistic regression analysis identified exposure to physician 4 and duration of ventilation as independent risk factors for colonization with MRSA (P < or = 0.008). Air cultures showed that physician 4 dispersed little S. aureus in the absence of a URI. After experimental induction of a rhinovirus URI, physician 4's airborne dispersal of S. aureus without a surgical mask increased 40- fold; dispersal was significantly reduced when physician 4 wore a mask (P < or = 0.015). CONCLUSIONS: Physician 4 became a "cloud adult," analogous to the "cloud babies" described by Eichenwald and coworkers who shed S. aureus into the air in association with viral URIs. Airborne dispersal of S. aureus in association with a URI may be an important mechanism of transmission of S. aureus.

Association of a Tourette-like syndrome with ofloxacin.

OBJECTIVE: To describe the association between the use of the fluoroquinolone ofloxacin in an elderly man and an unusual acute encephalopathy with characteristics suggestive of Tourette's syndrome. CASE SUMMARY: An unusual syndrome was observed in a 71-year-old man temporally related to the initiation of ofloxacin therapy that resolved completely after discontinuation of the drug. The most remarkable phenomena were spitting and profuse swearing; other features were echolalia, echopraxia, orofacial and limb automatisms, hypersalivation, and amnesia for the episode on recovery. The clinical syndrome had several features in common with Tourette's syndrome and possibly with frontal lobe onset complex partial seizures. The electroencephalographic, neuroradiologic, and cerebrospinal fluid examinations were normal. DISCUSSION: The reported neurotoxic effects of the fluoroquinolones include insomnia, seizures, delirium, and psychosis, best explained by the gamma-aminobutyric acid-antagonistic properties of this class of drugs. This is the first reported case of a Tourette-like syndrome associated with the use of any quinolone, suggesting a possible interaction with central dopaminergic neurotransmitter systems. CONCLUSIONS: Use of drugs such as ofloxacin that have improved central nervous system penetration, disease- or age-related reductions in renal function, concomitant use of drugs such as theophylline and nonsteroidal antiinflammatory drugs, and possibly increased pharmacodynamic sensitivity place the elderly at special risk for quinolone neurotoxicity. Dosing modifications and an awareness of possible central nervous system adverse effects are warranted.

Molecular analysis of bacterial pathogens in otitis media with effusion.

OBJECTIVE: To determine if the polymerase chain reaction (PCR) can detect bacterial DNA in pediatric middle ear effusions that are sterile by standard cultural methods. DESIGN: Single-center, blinded, comparative study of diagnostic assays. The PCR-based detection systems for Moraxella catarrhalis, Haemophilus influenzae, and Streptococcus pneumoniae were designed and validated using a battery of DNAs obtained from cultured bacteria. Chronic middle ear effusion specimens were collected and comparatively analyzed by culture and the PCR. SETTING: Tertiary care pediatric hospital. PATIENTS: A total of 97 middle ear effusions were collected from pediatric outpatients at Children's Hospital of Pittsburgh (Pa) during myringotomy and tube placement for chronic otitis media with effusion (duration > 3 months). All patients had failed multiple courses of antimicrobial therapy and were diagnosed by a combination of validated otoscopy and tympanograms. MAIN OUTCOME MEASURE: Differences in the percentage of positive test results between PCR-based assays and culture for M catarrhalis, H influenzae, and S pneumoniae. RESULTS: Of the 97 specimens of otitis media with effusion, 28 (28.9%) tested positive by both culture and PCR for M catarrhalis, H influenzae, or S pneumoniae. An additional 47 specimens (48%) were PCR positive/culture negative for these three bacterial species. Thus, 75 (77.3%) of the 97 specimens tested PCR positive for one or more of the three test organisms. The minimum number of bacterial genomic equivalents present in the average culture-negative ear was estimated to be greater than 10(4) based on dilutional experiments. CONCLUSIONS: The PCR-based assay systems can detect the presence of bacterial DNA in a significant percentage of culturally sterile middle ear effusions. While this finding is not proof of an active bacterial infectious process, the large number of bacterial genomic equivalents present in the ears is suggestive of an active process.

Evidence of nosocomial spread of Candida albicans causing bloodstream infection in a neonatal intensive care unit.

Candida albicans is an increasingly important bloodstream pathogen. We investigated a cluster of bloodstream infections in the neonatal intensive care unit (NICU) to determine whether nosocomial transmission occurred. Subjects included any patient in the NICU who developed clinically significant bloodstream infection with C. albicans from January 1984 to December 1987 (N = 7). Isolates were typed by restriction fragment length polymorphism analysis using a C. albicans-specific DNA probe (27A). Four of the neonates were infected from June to August 1984 (1.4 infections per 100 admissions) (the epidemic period) versus none in the period from January to May 1984, and three in the period from September 1984 to December 1987 (0.12 infections per 100 admissions) (P = .002). Three of the four patients in the epidemic period were infected with identical strains, readily distinguished from epidemiologically unrelated strains from the NICU. We conclude that nosocomial transmission of C. albicans occurred and that neonates in intensive care units may represent one group at increased risk.

Long-term efficacy of intranasal mupirocin ointment. A prospective cohort study of Staphylococcus aureus carriage.

BACKGROUND: We investigated the long-term effect of a single 5-day application of intranasal mupirocin calcium ointment on Staphylococcus aureus nasal and hand colonization. The subjects were 68 healthy volunteers who were health care workers with stable S aureus nasal carriage and who had participated in a randomized, double-blind placebo-controlled clinical trial of intranasal mupirocin ointment. METHODS: A 1-year prospective cohort study of S aureus nasal carriers after treatment with active drug or placebo was performed. Cultures were obtained from all subjects 6 and 12 months after therapy. All subjects returned for the 6-month visit; 63 (93%) were examined at 1 year. The major outcome measure was the relative proportion of any S aureus cultured at either site at 6 and 12 months. The S aureus isolates were typed by restriction endonuclease analysis of plasmid DNA and by antibiotic susceptibility tests; the similarity of nasal and hand isolate "fingerprints" was compared. RESULTS: At 6 months, nasal carriage was 48% in the treatment group vs 72% in controls (relative risk, 0.68; 95% confidence interval, 0.45 to 1.02; P = .054); at 1 year, nasal carriage was 53% vs 76%, respectively (relative risk, 0.70; 95% confidence interval, 0.48 to 1.02; P = .056). Hand carriage at 6 months was significantly reduced among mupirocin recipients relative to controls (15% and 48%; P = .04, adjusted for the baseline rate of hand carriage). Thirty-six percent of treated subjects were recolonized in the nares with a new strain at 1 year, whereas 34% had reisolation of the original strain after initially negative posttherapy cultures. During the year of follow-up, hand carriage was observed at least once in two thirds of the subjects. Nearly all of the hand isolates (87%) exactly matched the subjects' coincident nasal plasmid fingerprint and antibiogram type. CONCLUSIONS: A single brief treatment course of intranasal mupirocin was effective in reducing nasal S aureus carriage for up to 1 year. When S aureus was recovered after nasal decolonization, the new isolate was as likely to represent colonization with a new strain as reisolation of the original strain. Staphylococcus aureus hand carriage was significantly decreased 6 months after therapy, further implicating the nares as the primary reservoir site for hand carriage.

Elimination of coincident Staphylococcus aureus nasal and hand carriage with intranasal application of mupirocin calcium ointment.

OBJECTIVE: To determine the safety and efficacy of mupirocin calcium ointment in the elimination of Staphylococcus aureus nasal and hand carriage in healthy persons. DESIGN: A double-blind, placebo-controlled, randomized trial. SETTING: Clinical research unit of a tertiary medical center. SUBJECTS: Health care workers with stable S. aureus nasal carriage. INTERVENTIONS: Subjects (n = 68) were randomly assigned to receive either mupirocin or placebo intranasally twice daily for 5 days. MEASUREMENTS AND MAIN RESULTS: Cultures of the hands and nares were obtained at baseline and 72 hours after therapy. The nares were also cultured 1, 2, 4, and 12 weeks after therapy. Antimicrobial susceptibility testing and restriction endonuclease analysis of plasmid DNA were used to confirm strain identity. There were no serious side effects. Mupirocin decreased the frequency of S. aureus nasal carriage at each time interval: At 3 months, 71% of subjects receiving mupirocin remained free of nasal S. aureus compared with 18% of controls. This difference (53%; 95% CI; 26% to 80%) was significant (P less than 0.0001). Additionally, analysis of plasmid patterns showed that 79% of subjects in the mupirocin group were free of the initial colonizing strain at 3 months. The proportion of hand cultures positive for S. aureus in the mupirocin group after therapy was lower than in the placebo group (2.9% compared with 57.6%). This difference (53%; 95 CI, 30% to 80%) was significant, after adjustment for the frequency of hand carriage at baseline (P less than 0.0001). CONCLUSIONS: When applied intranasally for 5 days, mupirocin calcium ointment is safe and effective in eliminating S. aureus nasal carriage in healthy persons for up to 3 months and appears to have a corresponding effect on hand carriage at 72 hours after therapy.

Characterization of the sequence of colonization and nosocomial candidemia using DNA fingerprinting and a DNA probe.

The objective of this hospital-based study was to determine the relationship between colonizing and infecting strains of Candida species and Torulopsis glabrata. Surveillance cultures from high-risk patients were paired with subsequent bloodstream isolates. Organisms were typed by using restriction endonuclease digestion of chromosomal DNA with BstNI and EcoRI, followed by Southern hybridization with a DNA probe (pBD4) derived from Saccharomyces cerevisiae. Sixteen patients for whom documented colonization preceded documented bloodstream infection were identified. The mean time between obtainment of surveillance isolates and obtainment of bloodstream isolates was 8 days, with a range of 1 to 423 days. For 15 (94%) of 16 patients, the DNA fingerprint pattern (using BstNI) of the surveillance isolate was identical to that of the bloodstream isolate. Isolates from 13 (81%) of 16 patients were unique to those patients. Typing by Southern hybridization with the pBD4 probe was less discriminating. We conclude that for a well-defined subset of hospitalized patients who were colonized by Candida species before developing nosocomial candidemia, the colonizing and infecting strains were identical, suggesting endogenous acquisition of infection. Restriction endonuclease digestion of chromosomal DNA was shown to be a discriminating and reproducible typing method for Candida species and T. glabrata.