Mupirocin treatment of nasal staphylococcal colonization.

The effectiveness and safety of mupirocin calcium ointment applied to the anterior part of the nares for 5 days in the eradication of nasal carriage of Staphylococcus aureus was investigated in a placebo-controlled, double-blind study. Subjects were healthy medical center staff who had two positive cultures of the anterior nares for S aureus. Antimicrobial susceptibility, phage typing, and restriction endonuclease analysis of plasmid DNA were used to monitor the identity of relapsing and persisting strains. Mupirocin eliminated 74% of S aureus at early follow-up and 91% of original strains. At 4 weeks, 78% of the original strains were eradicated, whereas all of the placebo group remained colonized. Recolonization with mupirocin-resistant strains occurred in six patients, but these were of different phage and plasmid types from the original isolates. None of the subjects had serious adverse effects. Applied intranasally for 5 days, a calcium preparation of mupirocin in a paraffin base is effective in eliminating S aureus nasal carriage and is well tolerated.     

Staphylococcus aureus nasal carriage in 104 cirrhotic and control patients. A prospective study

BACKGROUND/AIMS: Bacterial infections, specially Staphylococcus aureus (S. aureus) septicemia, remain a leading cause of death following liver transplantation. It has been demonstrated that nasal carriage of S. aureus is associated with invasive infections in patients undergoing hemodialysis and could be decreased by use of antibiotic nasal ointment. However, in cirrhotic patients, the frequency of nasal carriage is unknown. The aims of this study were to determine the prevalence of S. aureus nasal carriage in cirrhotic patients and to assess nosocomial contamination. METHODS: One hundred and four patients were included in a prospective study, 52 cirrhotic and 52 control (hospitalized patients without cirrhosis or disease which might increase the rate of nasal carriage of S. aureus). On admission and after a few days of hospitalization, nasal specimens from each anterior naris were obtained for culture. S. aureus was identified by the gram strain, positive catalase and coagulase reactions; antibiotic susceptibility was determined using a disk-diffusion test. RESULTS: Both groups were similar with regard to age and sex. The prevalence of nasal colonization on hospital admission was 56% in cirrhotic patients and 13% in control patients (p = 0.001). After an average of 4 days, 42% of cirrhotics and 8% of control patients were colonized (p = 0.001), without any nosocomial contamination. Three strains out of 29 were oxacillin-resistant in cirrhotic patients, and none in controls (p>0.05). There was no statistical difference in carriage rate according to sex, age, cause of cirrhosis and Child-Pugh score. Previous hospitalization (OR, 6.3; 95% CI, 2.3 to 19.9; p = 0.0006) and cirrhosis (OR, 4.4; 95% CI, 1.5 to 13.4; p = 0.0048) were independent predictors of colonization. CONCLUSION: Cirrhotic patients had a higher S. aureus nasal carriage rate than control subjects. Previous hospitalization and cirrhosis diagnosis were correlated to nasal colonization. Further studies are necessary to determine if nasal decontamination could reduce S. aureus infections after liver transplantation.     

Identification of in vivo-expressed antigens of Staphylococcus aureus and their use in vaccinations for protection against nasal carriage

A spectrum of in vivo-expressed Staphylococcus aureus antigens was identified by probing bacteriophage expression libraries of S. aureus with serum samples from infected and uninfected individuals. Eleven recombinant antigenic proteins were produced, and specific antibody titers in a large collection of human serum samples were determined. Significantly increased concentrations of reactive immunoglobulin G (IgG) to 7 antigens were found in serum samples from ill individuals, compared with those in healthy individuals. Significantly higher concentrations of reactive IgG to 4 antigens, including iron-responsive surface determinant (Isd) A and IsdH, were found in serum samples from healthy individuals who were not nasal carriers of S. aureus, compared with those in healthy carriers. Vaccination of cotton rats with IsdA or IsdH protected against nasal carriage. Also, IsdA is involved in adherence of S. aureus to human desquamated nasal epithelial cells and is required for nasal colonization in the cotton rat model. Thus, vaccination with these antigens may prevent S. aureus carriage and reduce the prevalence of human disease.     

Host polymorphisms in interleukin 4, complement factor H, and C-reactive protein associated with nasal carriage of Staphylococcus aureus and occurrence of boils

BACKGROUND: Staphylococcus aureus is capable of persistently colonizing the vestibulum nasi. We hypothesized that polymorphisms in host inflammatory response genes and genetic variation in S. aureus contribute to susceptibility to S. aureus carriage and infection. METHODS: The prevalence of persistent nasal carriage of S. aureus in 3851 participants aged 61-101 years was 18% (678 of 3851 participants), whereas 73% of volunteers (2804 of 3851) were not colonized. A total of 1270 individuals had boils. Polymorphisms in TNFA (C -863T), IL4 (C -542T), CFH (Tyr402His), and CRP (C1184T, C2042T, and C2911G) were determined. Genetic similarity among 428 S. aureus isolates was determined by use of amplified fragment length polymorphism analysis (AFLP)-mediated genotyping. RESULTS: The IL4 -524 C/C host genotype was associated with an increased risk of persistent S. aureus carriage, irrespective of S. aureus AFLP genotype. The CRP haplotype 1184C; 2042C; 2911C was overrepresented in individuals who were not colonized . In individuals with boils, carriers of the CFH Tyr402 variant, and the CRP 2911 C/C genotype were overrepresented. CONCLUSION: Persistent carriage of S. aureus is influenced by genetic variation in host inflammatory response genes. As would be expected in multifactorial host-microbe interactions, these effects are limited. Interestingly, host genotype was associated with the carriage of certain S. aureus genotypes. Apparently, a close interaction between host and bacterial determinants are prerequisites for long-term colonization.     

Nasal carriage of and infection with Staphylococcus aureus in HIV-infected patients

BACKGROUND: Staphylococcus aureus is a common cause of serious infection in patients infected with HIV. OBJECTIVES: To evaluate risk factors for and quantitative effect of S. aureus infection in HIV-infected patients, with special attention to nasal carriage. DESIGN: Prospective, multihospital cohort study. SETTING: Three tertiary care Veterans Affairs Medical Centers. PARTICIPANTS: 231 ambulatory HIV-infected patients. RESULTS: Thirty-four percent of patients were nasal carriers of S. aureus. Of these patients, 38% were persistent carriers and 62% were intermittent carriers. Twenty-one episodes of infection occurred in 13 patients: Ten were bacteremias (including 2 cases of endocarditis), 1 was pneumonia, and 10 were cutaneous or subcutaneous infections. Seventeen (85%) of these episodes occurred in patients with CD4 counts less than 100 cells/mm3. Recurrent infections occurred in 3 of 7 patients who survived an initial S. aureus infection. The mortality rate was higher among patients with S. aureus infection than among those without infection (P = 0.03). Factors significantly associated with S. aureus infection were nasal carriage, presence of a vascular catheter, low CD4 count, and neutropenia. Molecular strain typing indicated that for 6 of 7 infected patients, the strain of S. aureus isolated from the infected sites was the same as that previously cultured from the nares. CONCLUSION: Nasal carriage is an important risk factor for S. aureus infection in HIV-infected patients. Controlled studies are indicated to determine whether eradication of nasal carriage in a selected subset of patients (for example, those with a low CD4 cell count) might prevent invasive S. aureus infection in patients with HIV infection.     

Methicillin-resistant Staphylococcus aureus prevalence in community in the east Delhi area

Methicillin-resistant Staphylococcus aureus (MRSA) continues to be an important nosocomial pathogen. Various hospital-based studies have described the incidence of MRSA and carriage of this organism in health care workers. Recently, even community acquired S. aureus strains have shown resistance to methicillin. This changing epidemiology prompted us to study the nasal carriage of MRSA amongst healthy individuals in a community. A total of 319 nasal swabs were taken from both anterior nares of healthy parents attending a well-baby clinic. Of these, 94 yielded growth of S. aureus (29.4%). Out of these 94 isolates, 17 (18.1%) were found resistant to oxacillin. These strains showed low level resistance only to clindamycin.     

Population dynamics of nasal strains of methicillin-resistant Staphylococcus aureus--and their relation to community-associated disease activity

BACKGROUND: Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) plays a key role in the epidemiology and pathogenesis of disease. The purpose of this study was to determine the characteristics and dynamics of nasal strains of MRSA, as well as their relation to community-associated disease activity. METHODS: This study is a cross-sectional survey and molecular epidemiologic analysis of nasal colonization by S. aureus in homeless and runaway youths, an underserved population at high risk for staphylococcal disease. RESULTS: Of the 308 study participants, 27.6% carried S. aureus, and 6.2% carried MRSA. Subgroups of individuals with increased MRSA carriage rates were also at highest risk for community-associated MRSA infection; these subgroups included individuals with either HIV infection or AIDS, injection drug users, patients with abscesses, and those recently hospitalized. Multilocus sequence typing and pulsed-field gel electrophoresis identified 2 genotypes--ST59:P (USA1000) and ST8:S (USA300)--that accounted for 84.2% (16/19) of the MRSA isolates carried. The genotypes were distinct from nosocomial genotypes endemic in the hospital, although they originated from individuals with prior exposure to health care. CONCLUSIONS: Comparison of MRSA strains from asymptomatic carriers versus concurrently collected community-associated clinical strains from patients treated at local health-care facilities allowed for the identification of 3 population dynamics of nasal strains of MRSA: (1) endemic clones--for example, ST8:C and ST59:P--sustained asymptomatic carriage and infection over prolonged periods; (2) an epidemic clone, ST8:S, demonstrated enhanced capacity for rapid transmission and widespread infections; and (3) an outbreak clone, ST30:Z (USA1100), was highly infectious but exhibited poor asymptomatic transmission.     

Staphylococcus aureus nasal carriage in rheumatoid arthritis: antibody response to toxic shock syndrome toxin-1.

OBJECTIVE: To determine the prevalence of Staphylococcus aureus nasal carriage and to compare antibody responses to two superantigens, staphylococcal toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin A (SEA), in rheumatoid arthritis patients and normal subjects. METHODS: 88 rheumatoid arthritis patients and 110 control subjects were cultured for nasal carriage of S aureus; 62 isolates were bacteriophage typed. Twenty five patients and 11 spouses were tested for antibodies to TSST-1, SEA, and sonicate extracts of Bacteroides fragilis and Escherichia coli; 19 patients were HLA-DR typed. RESULTS: 50% of patients and 33% of normal subjects were S aureus carriers. Bacteriophage typing of isolates suggested significant differences between strains isolated from the two groups. Patients showed higher IgG (P = 0.0025) and IgA (P = 0.0372) antibody levels to TSST-1 than normal spouses and these responses were not related to rheumatoid factor titres or HLA-DR type. CONCLUSION: When compared to normals, rheumatoid arthritis patients more often carry S aureus in their nasal vestibule, carry a distinct subpopulation of S aureus strains, and have higher average antibody levels to TSST-1.     

Prevalence of agr dysfunction among colonizing Staphylococcus aureus strains

Mutations in the staphylococcal virulence regulator gene agr frequently occur during Staphylococcus aureus infection. Whether agr-defective strains are fit for colonization, an important prerequisite for infection, is unknown. Screening by means of assays to detect delta-hemolysin activity and agr autoinducing peptide production indicated that 15 ( approximately 9%) of 160 healthy human subjects were colonized with an agr-defective strain or a mixture of agr-positive and -defective S. aureus strains. The presence of identical agr-defective strains in family members suggests that these strains are transmissible. Additionally, carriage of an agr-defective strain was associated with hospitalization, raising the possibility that such strains may be selected in a nosocomial setting.     

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.     

Isolation of enterotoxigenic Staphylococcus aureus from pet dogs and cats: a public health implication

Staphylococcus aureus is a globally distributed bacterium causing wide variety of illnesses in humans, which attributed to its ability to produce wide array of virulence factors, including enterotoxins that are responsible for staphylococcal food poisoning outbreaks. The current study was carried out to investigate the prevalence of enterotoxigenic S. aureus among pet dogs and cats and its public health implication. For this purpose, nasal, oral, and wound swabs were collected from 70 dogs and 47 cats, whereas nasal swabs were collected from 26 human contacts. All samples were examined for the presence of enterotoxigenic S. aureus by isolation of S. aureus in culture media and then tested by specific ELISA kits to detect the produced toxins in bacterial cultures. The prevalence of enterotoxigenic S. aureus was 10% and 2.1% for pet dogs and cats, respectively, whereas the nasal carriage rate in human contacts was 7.7%. The majority of animal isolates were obtained from mouth of the apparently healthy animals. All types of staphylococcal enterotoxins were detected in both animal and human isolates. High prevalence of enterotoxigenic S. aureus among pet dogs highlights the possibility of zoonotic transmission to human contacts leading to nasal and/or hand carriage of such strains; thus, pet animals may be incriminated in the epidemiology of household staphylococcal food poisoning outbreaks.     

Oral carriage of staphylococci in patients with rheumatoid arthritis.

OBJECTIVE: To determine the prevalence of oral staphylococcal carriage in patients with rheumatoid arthritis compared with healthy controls. METHODS: Fifty healthy adults, 25 healthy elderly volunteers and 25 patients with rheumatoid arthritis were studied. An oral rinse, tongue swab and nasal swab were collected for culture on blood agar and a range of selective agars. Isolates of staphylococci were identified and antibiotic sensitivity profiles determined by standard methods. RESULTS: Staphylococci were isolated from the mouths of 94% of the healthy adults, 24% of whom carried Staphylococcus aureus. All the healthy elderly carried oral staphylococci and 36% were colonized with S. aureus. Staphylococci were isolated from 96% of the rheumatoid arthritis patients and this group had the highest carriage rate of S. aureus (56%), significantly higher than the healthy adults (P < 0.05). In all three groups, Staphylococcus epidermidis was isolated from the mouths of > 80%. No methicillin-resistant strains of S. aureus were isolated. CONCLUSION: Oral carriage of S. aureus appears to be common in patients with rheumatoid arthritis and studies of the mouth as a source of infection in septic arthritis would be merited.     

Prevalence of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in the community

Recent reports indicate that community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections are increasing and may now involve persons without risk factors predisposing for acquisition. To estimate the extent of community MRSA in New York City, the prevalence of S. aureus and MRSA nasal colonization in a well-patient population of 500 children and guardians was determined. The prevalence of S. aureus nasal carriage was 35% for children and 28% for guardians. One person with predisposing risk factors was colonized with an MRSA, which was identified as the predominant clone found in New York City hospitals. A high degree of methicillin-susceptible S. aureus strain diversity was noted, with no apparent selection for specific clonal types. Thus, MRSA colonization is not ubiquitous in persons without predisposing risk outside of the health care environment. Bacterial competition and a lack of strong selection may limit the community spread of MRSA and can account for its sporadic distribution.     

Associations between Staphylococcus aureus Genotype, Infection, and In-Hospital Mortality: A Nested Case-Control Study

We screened 14,008 adult nonsurgical patients for Staphylococcus aureus nasal carriage at hospital admission and assessed them for invasive S. aureus disease and in-hospital mortality. Multilocus sequence typing was performed on endogenous invasive strains and nasal strains of matched asymptomatic carriers to investigate whether virulent clones could be identified in nasal carriers. Clonal complex (CC) 45 was significantly underrepresented (odds ratio [OR], 0.16 [95% confidence interval {CI}, 0.04-0.59]) and CC30 was overrepresented (not statistically significant) among invasive strains (OR, 1.91 [95% CI, 0.91-4.0]). The distribution of CCs of invasive S. aureus strains in noncarriers did not differ from that in carriers. Those infected with S. aureus strains belonging to a CC had higher mortality than those infected with strains not belonging to a CC (P<.05), which indicates the coevolution of S. aureus virulence and spread in humans.     

Investigation of colonization with methicillin-resistant and methicillin-susceptible Staphylococcus aureus in an outpatient population in Turkey

Methicillin-resistant Staphylococcus aureus (MRSA), known as a nosocomial pathogen, has been isolated from community-acquired infections since the 1980s. It has been reported that there are carriers of MRSA in the community although the rate of carriers is low and the most important risk factor of community-acquired carriage is hospitalization or referral to healthcare facilities. We attempted to investigate methicillin-resistant and methicillin-susceptible S. aureus colonization, respectively, in nasal and axillary swabs obtained from 500 patients without a history of hospitalization who were admitted to outpatient clinics and from 102 healthcare workers chosen as a control group. Of the patients, 9.4% had nasal S. aureus colonization without methicillin-resistant strains. Of the health care workers, 8.8% had S. aureus colonization without methicillin-resistant strains and only one worker had MRSA. The nasal carriage ratio of S. aureus in children was found to be 19.1% (22 of 115), and that in adults was 6.5% (25 of 385). The difference between the two age groups was determined as statistically significant (P = 0.006).     

Comparison of in vitro adherence of methicillin-sensitive and methicillin-resistant Staphylococcus aureus to human nasal epithelial cells.

Reported nasal carriage rates of personnel caring for patients with methicillin-resistant Staphylococcus aureus (MRSA) range from 1% to 6% in contrast to nasal carriage rates of 45%-65% for methicillin-sensitive S. aureus (MSSA) in health care personnel under nonepidemic conditions. One proposed explanation for these conflicting observations was examined, namely that MSSA and MRSA differ in their ability to adhere to nasal epithelial cells. The adherence of 6 genotypically distinct strains of MSSA and MRSA to nasal epithelial cells from 5 healthy donors was compared using a radioisotope assay system (coefficient of variation, 26%). The effect of pretreating epithelial cells with S. aureus-derived ribitol teichoic acid, a known adhesin of S. aureus for epithelial cells, was also examined. The mean (+/- SE) adherence of MRSA compared with MSSA in 108 assays was 125 +/- 11.9 versus 129 +/- 8.3 viable bacteria per cell (P = .67). Dose-dependent competitive inhibition by ribitol teichoic acid was linear and equivalent for MRSA and MSSA (r, .949, P less than .001). As these in vitro results correlate to adherence in vivo, it would be anticipated that MRSA and MSSA would have an equal likelihood of nasal carriage. A critical review of published epidemiologic studies comparing MRSA and MSSA carriage rates also supports this hypothesis.     

In vitro production of panton-valentine leukocidin among strains of methicillin-resistant Staphylococcus aureus causing diverse infections.

BACKGROUND: Community-acquired methicillin-resistant Staphylococcus aureus strains have recently been associated with severe necrotizing infections. Greater than 75% of these strains carry the genes for Panton-Valentine leukocidin (PVL), suggesting that this toxin may mediate these severe infections. However, to date, studies have not provided evidence of toxin production. METHODS: Twenty-nine community-acquired methicillin-resistant Staphylococcus aureus and 2 community-acquired methicillin-susceptible S. aureus strains were collected from patients with infections of varying severity. Strains were analyzed for the presence of lukF-PV and SCCmecA type. PVL production in lukF-PV gene-positive strains was measured by ELISA, and the amount produced was analyzed relative to severity of infection. RESULTS: Only 2 of the 31 strains tested, 1 methicillin-resistant Staphylococcus aureus abscess isolate and 1 nasal carriage methicillin-susceptible S. aureus isolate, were lukF-PV negative. All methicillin-resistant Staphylococcus aureus strains were SCCmec type IV. PVL was produced by all strains harboring lukF-PV, although a marked strain-to-strain variation was observed. Twenty-six (90%) of 29 strains produced 50-350 ng/mL of PVL; the remaining strains produced PVL in excess of 500 ng/mL. The quantity of PVL produced in vitro did not correlate with severity of infection. CONCLUSIONS: Although PVL likely plays an important role in the pathogenesis of these infections, its mere presence is not solely responsible for the increased severity. Factors that up-regulate toxin synthesis in vivo could contribute to more-severe disease and worse outcomes in patients with community-acquired methicillin-resistant Staphylococcus aureus infection.     

Nosocomial antibiotic-associated diarrhea associated with enterotoxin-producing strains of methicillin-resistant Staphylococcus aureus

OBJECTIVES: The aim of this study is to present new evidence that enterotoxin-producing strains of methicillin-resistant Staphylococcus aureus may cause nosocomial antibiotic-associated diarrhea. METHODS: We conducted a prospective study that utilized standard methods to exclude other bacterial, parasitic, and viral pathogens as causes of nosocomial diarrhea in patients with heavy growth of methicillin-resistant S. aureus in their stool. Staphylococcal enterotoxin assays were performed on S. aureus strains recovered from patients' stools and on stool specimens from affected patients. Retrospective cohort studies compared the severity of diarrhea in patients with methicillin-resistant S. aureus-associated diarrhea with that of patients whose stool did not contain the organism and with patients colonized or infected with enterotoxin-negative methicillin-resistant S. aureus strains. RESULTS: During an 18-month period, 11 patients had nosocomial antibiotic-associated diarrhea associated with enterotoxin-producing strains of methicillin-resistant S. aureus. Other common bacterial, parasitic, and viral pathogens were excluded. S. aureus strains from the 11 patients produced staphylococcal enterotoxin A, A and B, or D. Eighty-nine percent of patients had the same enterotoxin(s) in stool specimens as produced by the strain recovered from their stool. Case patients had a greater number of days of diarrhea than patients without methicillin-resistant S. aureus in their stool (p < 0.001), or randomly selected patients colonized or infected with enterotoxin-negative methicillin-resistant S. aureus (p < 0.001). CONCLUSIONS: Our findings provide evidence that enterotoxin-producing strains of methicillin-resistant S. aureus may cause nosocomial antibiotic-associated diarrhea. Greater recognition of this disease should result in more rapid and appropriate treatment of affected patients.     

Transmission of Staphylococcus aureus from maternity unit staff members to newborns disclosed through spa typing

BACKGROUND: We observed previously that newborn infants are colonized with Staphylococcus aureus, even if their mothers do not carry S aureus. This observation indicated a cross colonization, and, thus, a risk for nosocomial infection, although the infants are roomed in with their mothers. METHODS: The S aureus colonization of infants, their parents, and staff members was measured at 3 maternity units. Possible transmission routes were determined using spa typing of S aureus isolates. RESULTS: Infants had the highest S aureus carriage (45%) compared with fathers (39%), mothers (27%), and staff members (27%). In 13 out of 44 colonized infants, transmission from staff members was indicated. This transmission was more frequent than was transmission from their own parents (11 cases), and occurred even in cases when parents were colonized with S aureus of other spa types. CONCLUSIONS: We confirm a high level of transmission of S aureus from staff members to infants, indicating a risk for patient safety, which necessitates continuing work with implementing scientific evidence for infection control. The spa typing is a rapid and valuable epidemiological tool, and it can be used in improving hospital hygiene control programs.