Comparative study of mupirocin and oral co-trimoxazole plus topical fusidic acid in eradication of nasal carriage of methicillin-resistant Staphylococcus aureus. Randomized, placebo-controlled, double-blind trial to evaluate the efficacy of mupirocin for eradicating carriage of methicillin-resistant Staphylococcus aureus. Emergence of ciprofloxacin resistance in nosocomial methicillin-resistant Staphylococcus aureus isolates. Resistance during ciprofloxacin plus rifampin therapy for methicillin-resistant S aureus colonization. Relative importance of antibiotic and improved clearance in topical treatment of chronic mucopurulent rhinosinusitis. A controlled study. Preoperative therapeutic considerations in chronic suppurative otitis media. Antimicrobial prophylaxis in patients with rhinorrhea or otorrhea: a double-blind study. Evaluation of an intervention designed to decrease the rate of nosocomial methicillin-resistant Staphylococcus aureus infection by encouraging decreased fluoroquinolone use. [Antimicrobial therapy in chronic suppurative otitis media]. A single topical agent is clinically equivalent to the combination of topical and oral antibiotic treatment for otitis externa.
Mupirocin is a topically applied drug that is very active in the eradication of nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA). However, studies designed to compare mupirocin treatment with other antimicrobial regimens are lacking. We therefore conducted an open, prospective, randomized, controlled trial to compare the efficacy and safety of mupirocin versus those of oral co-trimoxazole plus topical fusidic acid (both regimens with a clorhexidine scrub bath) for the eradication of MRSA from nasal and extranasal carriers of MRSA. The eradication rates with mupirocin and co-trimoxazole plus fusidic acid at 2, 7, 14, 21, 28, and 90 days were 93 and of 93, 100 and 100, 97 and 94, 100 and 92, 96 and 95, and 78 and 71%, respectively, for nasal carriage. At 7, 14, and 28 days the eradication rates for extranasal carriage by the two regimens were 23 and 74, 83 and 76, and 45 and 69%, respectively. The efficacies and safety of both regimens were similar. The MRSA isolates were not resistant to the study drugs either at the baseline or at follow-up. These results suggest that mupirocin and co-trimoxazole plus fusidic acid, both used in conjunction with a chlorhexidine soap bath, are equally effective and safe for the eradication of MRSA from nasal and extranasal MRSA carriers. Mupirocin was easier to use but was more expensive. Mupirocin has been widely used for the clearance of nasal methicillin-resistant Staphylococcus aureus (MRSA) carriage during outbreaks, but no placebo-controlled trial has evaluated its value for eradicating MRSA carriage at multiple body sites in settings where MRSA is not epidemic. In a 1,500-bed teaching hospital with endemic MRSA, 102 patients colonized with MRSA were randomized into a double-blind, placebo-controlled trial and treated with either mupirocin (group M) or placebo (group P) applied to the anterior nares for 5 days; both groups used chlorhexidine soap for body washing. Follow-up screening, susceptibility testing, and genotyping were performed to evaluate treatment success, mupirocin or chlorhexidine resistance, and exogenous recolonization. At baseline, MRSA carriage was 60% in the nares, 38% in the groin, and 62% in other sites (skin lesions, urine). The MRSA eradication rate (all body sites) was 25% in group M (12 of 48 patients), compared to 18% in group P (9 of 50 patients; relative risk [RR], 0.72; 95% confidence interval [CI95], 0.33 to 1.55). At the end of follow-up, 44% of patients (19 of 43) were free of nasal MRSA in group M, compared to 23% (11 of 44) in group P (RR, 0.57; CI95, 0.31 to 1.04). Ten patients developed MRSA infections (three in group M and seven in group P). One mupirocin treatment failure was due to exogenous MRSA recolonization. No MRSA isolate showed chlorhexidine resistance or high-level mupirocin resistance; however, we observed an association (P = 0.003) between low-level mupirocin resistance at study entry (prevalence, 23%) and subsequent treatment failure in both study arms. These results suggest that nasal mupirocin is only marginally effective in the eradication of multisite MRSA carriage in a setting where MRSA is endemic. We initiated a randomized, single-blinded trial of ciprofloxacin plus rifampin vs sulfamethoxazole and trimethoprim plus rifampin in the therapy for patients who underwent colonization with methicillin-resistant Staphylococcus aureus (MRSA). Patients who were colonized with MRSA received 2 weeks of either regimen. The study was terminated after the enrollment of 21 subjects due to the recognition of ciprofloxacin resistance in 10 of 21 new MRSA isolates during the last 2 months of the study. Five of the 10 patients with ciprofloxacin-resistant MRSA isolates had never received ciprofloxacin. Long-term (6-month) eradication had been achieved in only three of 11 ciprofloxacin plus rifampin and four of 10 sulfamethoxazole and trimethoprim plus rifampin recipients. The use of this new fluoroquinolone for the eradication of MRSA colonization is usually not effective and may risk the development of ciprofloxacin resistance in MRSA within the hospital environment. 50 patients with chronic mucopurulent rhinosinusitis were randomly allocated to treatment with nasal sprays of dexamethasone, tramazoline, and neomycin, dexamethasone and tramazoline with no antibiotic, or matched placebo (propellant alone) four times daily to both nostrils for 2 weeks. The patients were assessed in a double-blind manner for symptomatic response and improvement in nasal mucociliary clearance, nasal airway resistance, sinus radiographs, and intranasal bacteriology and appearance. Both active preparations (with antibiotic 14 of 20 patients responded; without antibiotic 12 of 20 patients responded) were more effective than the placebo (2 of 10 patients responded). There was no significant difference in response between the active preparations with and without antibiotic. Thus, in treatment of chronic mucopurulent rhinosinusitis, reduction of the inflammatory response and decongestion make topical antibiotic unnecessary, probably by allowing host clearance mechanisms to recover. The present randomized, prospective study of 119 cases of chronic suppurative otitis media compares the effectiveness of inexpensive, atoxic, nonallergenic disinfectants applied locally, to that of a number of occasionally toxic antimicrobial chemotherapeutic agents, administered systemically. Systemic treatment resulted in a cure rate of 53.5% (SEp = 5.9%) while ototopical treatment resulted in a 39.5% cure rate (SEp = 7%). Eradication of pathogens or colonization by a nonpathogen occurred in 50.7% (SEp = 5.9%) with systemic treatment, and in 39.5% (SEp = 7%) with ototopical treatment. Bacteriological modification was 2.5 times more frequent with systemic treatment than with ototopical treatment. No recurrences were noted with ototopical treatment, while 13% to 36% recurrence rates were noted in various subgroups of cases treated systemically. Cure rates achieved with particular drug regimens (administration based on sensitivity tests in vitro) were: Azactam 25% (5%-57% confidence limits), sulfamethoxazole plus trimethoprim 58.6% (38%-76%), ciprofloxacin 87.5% (47%-99%), ciprofloxacin plus metronidazole 90% (55%-99%). Cure rates with other drugs were inconclusive because of the limited number of observations. A controlled double-blind study was performed on patients with injury to the head and face which had caused rhinorrhea or otorrhea. The patients were treated, at the time of the admission to the hospital, with penicillin (20 mega-units daily) or a placebo. A total of 52 patients was studied, 26 in each treatment group. Meningitis developed in one patient in the placebo group. Staphylococcus epidermidis (sensitive to penicillin) was the causative pathogen in this patient who also had a retained intraventricular foreign body. The frequency of extra-neurological infections and of asymptomatic pulmonary bacterial colonization was similar in both groups, but frequency of asymptomatic bacteriuria was higher in the placebo-treated patients. Society for Health Care Epidemiology guidelines recommend decreasing the use of fluoroquinolone antibiotics in institutions where methicillin-resistant Staphylococcus aureus (MRSA) is endemic. We evaluated whether an intervention to limit fluoroquinolone use was associated with a lower rate of nosocomial MRSA infection and summarized changes in antibiotic use, changes in other variables potentially correlated with a lower rate of MRSA infection, and rates of nosocomial infections due to other pathogens.
                Single-center quasi-experimental design. A time series of nosocomial MRSA infections was measured at monthly intervals from July 2001 through June of 2004; there were 80 MRSA infections recorded. Segmented regression analysis (ie, quasi-Poisson generalized linear models) was used to evaluate variables possibly associated with the nosocomial MRSA infection rate.
                An 87-bed Veterans Affairs teaching hospital with an extended-care facility.
                A physician-directed computer-generated intervention designed to limit the use of fluoroquinolone antibiotics was initiated, and institutional changes in antibiotic use and nosocomial MRSA infection rates were tracked.
                After the intervention, fluoroquinolone use decreased by approximately 34%, and levofloxacin use decreased by approximately 50%. Decreased fluoroquinolone use was offset by increased cephalosporin, piperacillin-tazobactam, and trimethoprim-sulfamethoxazole use. The nosocomial MRSA infection rate decreased from 1.37 to 0.63 episodes per 1,000 patient-days after the study intervention (P=.02). Coagulase-negative Staphylococcus and Enterococcus infection rates also decreased. However, the rate of infection with gram-negative organisms increased. The rate of MRSA infection was positively correlated with levofloxacin use (P=.01) and azithromycin use (P=.08), whereas it was negatively correlated with summer season (P=.05). In a subsequent model, the rate of MRSA infection was negatively correlated with the study intervention (P=.04).
                Reduction in the institutional use of fluoroquinolones may be associated with a lower nosocomial MRSA infection rate. A randomized study was made of 125 patients with chronic middle ear infection. The most frequently isolated microorganisms were: Pseudomonas aeruginosa, Staphylococcus aureus and Enterobacteriaceae. Ciprofloxacin is very active against the microorganisms usually isolated and it has been shown to provide effective therapy in ear infections. In order to study the effectiveness of ciprofloxacin in chronic otitis media, we selected four different treatment groups: oral ciprofloxacin (500 mg/12 h); 0.5 and 0.2% topical solutions of ciprofloxacin (3 drops/8 h), and oral ciprofloxacin plus 0.2% topical solution. Topical polymyxin and neomycin were used as controls. Topical ciprofloxacin (0.2%) was the most effective regimen of those tested for the treatment of chronic otitis media. To demonstrate clinical equivalence (statistical noninferiority) of topical ciprofloxacin and hydrocortisone (CHC, Cipro HC) and topical neomycin/polymyxin b/hydrocortisone (NPH, Cortisporin) with systemic amoxicillin (AMX, Amoxil), for treatment of acute otitis externa (AOE).
                Randomized, active-control, observer-blind, multicenter trial.
                Altogether, 206 patients were enrolled (CHC, 106; NPH + AMX, 100). Patients were > or =1 year of age, had AOE >2 days with at least mild symptoms, and gave informed consent. All were evaluable for safety, and 151 were evaluable for efficacy.
                Ciprofloxacin and hydrocortisone 3 drops twice daily for 7 days (adults and children) or NPH 4 drops (adults) or 2 drops (children) with AMX 250 mg (adults and children) 3 times daily for 10 days, as directed in approved product labeling.
                The primary efficacy variable was response to therapy 7 days after treatment ended (test of cure). Secondary variables included time to end of pain, symptom scores (otalgia and tenderness) and microbiological eradication. Noninferiority was declared if the lower confidence limit around the measurement difference was above -10 (nearer zero).
                Response to therapy was higher for CHC (95.71% vs 89.83%) but was statistically noninferior (lower confidence limit, -4.98) to NPH + AMX. Median time to end of pain was 6 days for both groups. Noninferiority was declared for symptom scores at all measurement periods and for microbiological eradication. No serious adverse events related to treatment were reported.
                Ciprofloxacin and hydrocortisone is clinically equivalent to NPH + AMX for the treatment of AOE in adults and children. However, low systemic exposure, absence of ototoxicity, and less frequent dosing clearly favor Cipro HC.
There is insufficient evidence to support use of topical or systemic antimicrobial therapy for eradicating nasal or extra-nasal MRSA. There is no demonstrated superiority of either topical or systemic therapy, or of combinations of these agents. Potentially serious adverse events and development of antimicrobial resistance can result from therapy.