Emergence of mupirocin-resistant Staphylococcus aureus in chronic peritoneal dialysis patients using mupirocin prophylaxis to prevent exit-site infection.

OBJECTIVE: To determine the prevalence of the carriage of Staphylococcus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), and mupirocin-resistant Staphylococcus aureus (MuRSA) in chronic peritoneal dialysis (CPD) patients after 4 years of prophylactic mupirocin application to the exit site, in a peritoneal dialysis unit. METHODS: Three swabs were collected from the nares, axillae/groin, and exit site, respectively, from 149 patients on CPD between May and July 2001. All swabs were cultured on solid selective agar (mannitol salt agar) and in mannitol salt broth. Staphylococcus aureus isolates were tested for methicillin resistance using oxacillin screening plates, and mupirocin resistance using E-test strips. Low-level MuRSA was defined as minimum inhibitory concentration (MIC) of 4 mg/mL or more, and high-level MuRSA as MIC of 256 mg/mL or more. RESULTS: Staphylococcus aureus was isolated from 26 (17%) patients (25 from nares/axilla/groin, and 1 from the exit site). High-level MuRSA was isolated from 4 patients (3% of the total study population; 15% of total SA isolates). No MRSA was detected. One patient with high-level MuRSA had peritonitis due to SA, resulting in treatment failure and catheter loss, soon after the swabs were collected for the study. CONCLUSION: We report the emergence of high-level MuRSA in CPD patients after a 4-year practice of continuous use of mupirocin in a small number of patients in our unit. Our results may have significant implications for the future practice of prophylactic use of mupirocin by CPD patients to prevent exit-site infection.     

Sources of Staphylococcus aureus for patients on continuous ambulatory peritoneal dialysis.

OBJECTIVE: This study was designed to determine whether family members and health care workers are a source of Staphylococcus aureus for patients on peritoneal dialysis. DESIGN: Over 36 months, cultures were obtained from the nares of patients, family members that cared for the patients' catheters, and health care workers in a dialysis unit. Pulsed-field gel electrophoresis was performed on all S. aureus isolates. SETTING:A university-based peritoneal dialysis program. PARTICIPANTS: 74 patients, 32 family members, and 17 health care workers. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The number of patients that acquired S. aureus strains during the study period. RESULTS: Of the 48 patients whose initial nares cultures were negative, 7 (15%) acquired S. aureus strains. Overall, 24 of 53 (45%) patients that had 2 or more cultures obtained during the study gained strains. Potential sources were not identified for strains gained by 11 (46%) patients. Five patients appeared to acquire their strains from family members; however, other patients also shared related strains; 8 patients acquired strains shared by other patients. CONCLUSIONS: Family members and other patients appeared to be important sources of S. aureus for patients on peritoneal dialysis. Health care workers that carry S. aureus transiently may be important intermediaries. Good hand hygiene is essential to prevent transmission of S. aureus to these susceptible patients.     

Treatment of Pseudomonas infections in peritoneal dialysis patients

Pseudomonas species infections in the peritoneal dialysis population consist primarily of peritonitis or exit site infections. These organisms have traditionally proven difficult to eradicate, and the standard antibiotic regimen has carried the potential for nephrotoxicity. At our institution, all peritoneal dialysis patients with Pseudomonas exit site infections or peritonitis were treated with an antibiotic combination of intraperitoneal ceftazidime and oral ciprofloxacin. Treatment duration was dependent upon the site of infection. Recurrent exit site infections were treated with a repeated course of the antibiotics, and with surgical debridement and subsequent shaving of the external cuff of double-cuffed catheters. We saw a total of 11 Pseudomonas aeruginosa exit site infections in 7 patients (4 recurrent). Patients with recurrent infections were subsequently cured with the regimen as outlined above. Of 7 patients with Pseudomonas species peritonitis (aeruginosa, fluorescens, stutszeri, and maltophilia), 5 were cured with the initial antibiotic regimen. The 2 failures were both infected with Pseudomonas maltophilia, which is consistent with observed organism sensitivity data. The combination of ceftazidime and ciprofloxacin with the option for surgical debridement of the external cuff (in exit site infections) appears effective in the treatment of Pseudomonas species infections in the peritoneal dialysis population. Sensitivity data should be used to adjust the antibiotic regimen when appropriate.     

Peritoneal defence mechanisms and Staphylococcus aureus in patients treated with continuous ambulatory peritoneal dialysis (CAPD)

Peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients due to S. aureus is associated with an adverse clinical outcome, suggesting impaired clearance of this organism by the host. The ability of peritoneal macrophages (PM0) derived from CAPD patients to take up S. aureus and mount a respiratory burst was investigated. Whilst significant activity was observed in the absence of opsonin, both parameters of phagocytosis were augmented by addition of 20% pooled human serum (PHS), complement-depleted PHS, and fibronectin. When used as sole opsonin, fibronectin resulted in a dose-related increase in chemiluminescent response by both blood neutrophils and PM0. The opsonic activity of dialysis effluent, as judged by neutrophil chemiluminescence, correlated with IgG and fibronectin content, but not with complement as assessed by C3 levels. The addition of urokinase to dialysate improved its opsonic properties whilst having no effect on the activity of PHS-20%; this would suggest that the formation of fibrin in dialysate, promoted by S. aureus, interferes with phagocytosis. This and the low IgG, complement and fibronectin levels in dialysate may explain in part the relatively poor clearance of this organism from the peritoneum.     

Successful single-dose prophylaxis of Staphylococcus aureus foreign body infections in guinea pigs by fleroxacin.

Single-dose administration of fleroxacin was evaluated as a means of preventing foreign body infection due to staphylococci. Tissue cages were implanted into guinea pigs and subsequently infected (100% rate) with 10(2) or more CFU of Staphylococcus aureus Wood 46. When a single dose of 30 mg of fleroxacin or vancomycin per kg of body weight was administered intraperitoneally, bactericidal levels of the antimicrobial agent were found in the tissue cage fluid after 3 h (when guinea pigs were inoculated with S. aureus) and during the next 24 h. Either fleroxacin or vancomycin successfully prevented experimental infection in all tissue cages challenged by 10(2) CFU of S. aureus Wood 46. When tissue cages were challenged with 10(4) CFU of S. aureus Wood 46, however, fleroxacin was more effective than vancomycin (P less than 0.05) in reducing colony counts below the detection limit of 10 CFU/ml in the inflammatory fluid of all tissue cages during the initial 48 h. In contrast to their initially different actions, the effects of the antibiotics were similar after 7 days, mostly because bacterial regrowth occurred more frequently in the fleroxacin-treated than in the vancomycin-treated tissue cages. These data show that experimental infections of subcutaneous tissue cages are a useful model for studying the prophylaxis of foreign body infections with antimicrobial agents.     

Ciprofloxacin for methicillin-resistant Staphylococcus aureus infections.

Thirty-seven patients with methicillin-resistant Staphylococcus aureus infections and/or colonization were treated with oral ciprofloxacin (750 mg twice a day). Clinical cure or improvement of infections occurred in 91% of the patients, and bacteriologic cure occurred in 60%. Ciprofloxacin therapy suppressed methicillin-resistant S. aureus colonization in 55% of the patients. Ciprofloxacin-resistant strains emerged in 6 of the 37 patients.     

Effect of preventing Staphylococcus aureus carriage on rates of peritoneal catheter-related staphylococcal infections. Literature synthesis.

OBJECTIVE: To determine whether specific preventive measures reduce the rate of peritoneal catheter-related infections and peritoneal catheter loss due to Staphylococcus aureus. DESIGN: Structured literature synthesis. METHODS: Relevant studies were identified by MEDLINE search, from personal files, and from the reference lists of retrieved articles. We analyzed English-language studies on treatment targeted at S. aureus, with at least 10 subjects and at least 3 months of follow-up, and data on staphylococcal peritoneal dialysis catheter infections. We excluded noncontrolled studies. Two investigators abstracted data using a structured form. RESULTS: We evaluated six studies with concurrent controls and eight studies with historical controls. In one randomized, placebo-controlled, blinded study, periodic nasal mupirocin ointment reduced the rate of staphylococcal exit-site infection from 0.42 to 0.12 episodes/patient-year (p = 0.006), but had no effect on the rates of staphylococcal tunnel infection, peritonitis, or catheter loss. In one randomized study without placebo control, periodic oral rifampin reduced the rate of staphylococcal exit-site infection from 0.65 to 0.22 epi/pt-yr (p = 0.011), but had no effect on the rate of staphylococcal peritonitis. In another nonblinded, randomized, controlled study, the use of either rifampin or mupirocin was associated with low rates of staphylococcal catheter infections and catheter loss. In one study with historical controls, the rate of staphylococcal exit-site infection and peritonitis was lower after oral rifampin prophylaxis. In seven other studies comparing nasal or exit-site mupirocin to historical controls, the rate of staphylococcal exit-site infection decreased from 0.17 to 0.05 epi/pt-yr, the rate of staphylococcal peritonitis decreased from 0.18 to 0.06 epi/pt-yr, and the rate of catheter loss decreased from 0.09 to 0.05 epi/pt-yr during the mupirocin period. CONCLUSION: The literature provides strong evidence that staphylococcal carriage prophylaxis using either oral rifampin or mupirocin ointment in the nares or exit site reduces significantly the rate of exit-site infection due to Staphylococcus aureus. Weaker evidence based on studies with historical controls suggests that rifampin or mupirocin prophylaxis also reduces the rate of staphylococcal peritonitis and peritoneal catheter loss. Studies with a stronger level of evidence are needed to verify this last point.     

Community-associated Staphylococcus aureus infections in children

Staphylococcus aureus is an important human pathogen that affects children worldwide. The number of publications discussing community-associated S. aureus infections, particularly in children, adolescents and young adults, has increased in recent years. This is related to the emergence and worldwide spread of community-associated methicillin-resistant S. aureus and the increase in severe life-threatening community-associated S. aureus infections. The increase in severity has been seen with both methicillin-resistant and methicillin-susceptible strains. This suggests that other virulence factors might be associated with the observed trend. Panton–Valentine leukocidin is a distinctive virulence factor associated with a highly aggressive and often fatal form of community-acquired infections. We propose that empiric treatment should be adapted to the type of infection and the resistance profile present in each country or region. In cases of severe infection, a combination of antibiotics, including at least one molecule active against protein synthesis such as clindamycin or linezolid, will be needed.     

Methicillin-susceptible Staphylococcus aureus nasal colonization and the risk of subsequent methicillin-resistant Staphylococcus aureus infections among hospitalized patients

Few data exist on the risk of methicillin-resistant Staphylococcus aureus (MRSA) infections among known methicillin-susceptible S. aureus (MSSA) carriers. In a cohort of 2991 hospitalized MSSA carriers, 22 (22%) of 98 S. aureus infections that occurred within a subsequent 6-month period were caused by MRSA. Recent fluoroquinolone use was an independent predictor of MRSA infections (P < .001).     

Staphylococcus aureus nasal carriage, exit-site infection and catheter loss in patients treated with continuous ambulatory peritoneal dialysis (CAPD)

Over a three-year period, 217 episodes of bacterial peritonitis occurred in 183 patient years. Thirty-seven episodes were due to Staphylococcus aureus and 19 (51%) of these required removal of the catheter to eradicate infection. This compared with catheter loss in 4/63 (6.3%) coagulase negative staphylococci infections (p less than 0.001); 7/67 (9.5%) culture negative peritonitis (p less than 0.001); and 10/30 (33.3%) episodes due to gram-negative organisms (p less than 0.05). Over half (51.3%) the episodes due to S. aureus were associated with exit-site infections, and this rose to 100% (10/10) with recurrent peritonitis (p less than 0.01). A prospective analysis of nasal carriage and exit-site infections due to S. aureus was carried out in 87 patients. Exit-site infections were present in 21 (24%), almost entirely due to different strains as judged by sensitivity patterns and phage typing. Nasal carriage, defined as two positive swabs within the study period, was present in 20 (23%) patients. Fourteen (70%) of these had exit-site infections due to the same strain as that isolated from the nose, whereas no patient grew different strains from either site. Nasal carriage increased the risk of infection sixfold (p less than 0.001).     

Community-acquired methicillin-resistant Staphylococcus aureus infections

Staphylococcus aureus causes a variety of minor diseases but also is responsible for staphylococcal pneumonia and sepsis, both of which can be fatal. It is thought to be responsible for many of the pneumonia deaths associated with the influenza pandemics of the 20th century. The introduction of penicillin in the 1940s greatly improved the prognosis for patients with severe staphylococcal infections. However, after a few years of clinical use, most staphylococcal strains were able to hydrolyze penicillin by producing b-lactamases, making penicillin a useless antibiotic to treat staphylococcal infections caused by b-lactamase-producing S aureus. Methicillin, a semisynthetic penicillin introduced in 1959, was specifically designed to be resistant to b-lactamase degradation, but resistance developed soon after its introduction into clinical practice. Methicillin-resistant S aureus (MRSA) was first reported in the United Kingdom in 1961, followed by reports from other European countries, Japan, and Australia. The first reported case of MRSA in the United States was in 1968. Currently, MRSA is an important pathogen in nosocomial infections and is a problem in hospitals worldwide, and it is increasingly recovered from nursing home residents with established risk factors. More recently, community acquired MRSA infections have been documented among healthy individuals with no recognizable risk factors, and it seems clear that community-acquired MRSA (CA-MRSA) strains are epidemiologically and clonally unrelated to hospital-acquired strains. This review focuses on the epidemiology, clinical significance, and virulence markers of CA-MRSA infections.     

Management of Staphylococcus aureus infections

Because of high incidence, morbidity, and antimicrobial resistance, Staphylococcus aureus infections are a growing concern for family physicians. Strains of S. aureus that are resistant to vancomycin are now recognized. Increasing incidence of unrecognized community-acquired methicillin-resistant S. aureus infections pose a high risk for morbidity and mortality. Although the incidence of complex S. aureus infections is rising, new antimicrobial agents, including daptomycin and linezolid, are available as treatment. S. aureus is a common pathogen in skin, soft-tissue, catheter-related, bone, joint, pulmonary, and central nervous system infections. S. aureus bacteremias are particularly problematic because of the high incidence of associated complicated infections, including infective endocarditis. Adherence to precautions recommended by the Centers for Disease Control and Prevention, especially handwashing, is suboptimal.