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Clinical features and genotyping analysis of community-acquired methicillin-resistant Staphylococcus aureus infections in Taiwanese children.

BACKGROUND: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection in children without health care-associated risk factors has emerged. To evaluate the clinical features and genotyping analysis of CA-MRSA in children in Taiwan, we conducted this study. METHODS: Between July 2000 and June 2001, 198 episodes of S. aureus infection were identified in 191 children hospitalized at Chang-Gung Children's Hospital. The medical records of these children were retrospectively reviewed. The MRSA clinical isolates from each episode of infection, if available, were collected for pulsed-field gel electrophoresis (PFGE) typing and staphylococcal cassette chromosome mec (SCCmec) type determination. RESULTS: Among the 198 episodes of S. aureus infection, MRSA accounted for 47% of 114 CA infections and 62% of 84 hospital-acquired (HA) infections, respectively. Among 54 CA-MRSA infections, 32 episodes (59%) occurred in children without risk factors. Similar to HA-MRSA isolates, these CA-MRSA isolates were also multiresistant, with a high rate of resistance to clindamycin (93%) and erythromycin (94%), but 91% of them were susceptible to trimethoprim/sulfamethoxazole. Superficial soft tissue infection was the most common presentation, accounting for 65% of CA-MRSA infections. All 54 children with CA-MRSA infection recovered without sequelae, though 63% of 35 children with superficial soft tissue infection were treated with in vitro nonsusceptible antibiotics. Of the 83 clinical isolates (40 CA, 22 with no identified risk) available for analysis, 6 genotypes with 30 subtypes were identified. Three major PFGE patterns were identified, accounting for 94% of the isolates (92.5% for CA isolates, 95% for HA isolates). Type IV SCCmec was carried by 25 and 40% of CA and HA isolates, respectively. CONCLUSION: In Taiwan, MRSA was prevalent among pathogens of CA infections in children, and these CA isolates were multiresistant and genetically associated with HA isolates. In an area with a high prevalence of methicillin resistance, for children with putative S. aureus infection, even community-acquired, a glycopeptide-containing regimen should be considered for initial empirical therapy in the case of serious infection.

Adolescent↗

The efficacy and safety of linezolid as treatment for Staphylococcus aureus infections in compassionate use patients who are intolerant of, or who have failed to respond to, vancomycin.

OBJECTIVE: The incidence of infections caused by methicillin-resistant Staphylococcus aureus continues to increase annually. Unfortunately, only a few therapeutic agents are available for the treatment of patients with such infections and all of the existing drugs have limitations. A pressing need exists, therefore, to identify new antibiotics for use in this clinical setting. The efficacy and safety of linezolid were studied in a compassionate use treatment programme and the results of treating a subset of patients with S. aureus infections are presented here. METHODS: Patients received linezolid in a dosage of 600 mg intravenously (iv) and/or orally twice daily. Clinical and bacteriological responses were assessed after a minimum of 7 days and following completion of therapy. RESULTS: Seven hundred and ninety-six patients who suffered 828 episodes of infection were enrolled in the linezolid compassionate use protocol. Of these, 183 patients received linezolid for 191 infections caused by S. aureus; in 151 cases, patients were intolerant of vancomycin, had a mixed S. aureus/vancomycin-resistant enterococcal infection or had no iv access, and, in 40 cases, patients had failed to respond to treatment with vancomycin. The median age of the patients was 57 years (range 14-93 years) and 53.9% were female. The predominant sites of infection were as follows: bone or joint (27.2%); skin and skin structure (25.1%); bloodstream (20.9%); and lower respiratory tract (12.6%). The clinical success rates in the clinically evaluable and all-treated populations were 83.9% and 62.3%, respectively, whereas the bacteriological eradication rates were 76.9% and 70.2% in the bacteriologically evaluable and all-treated populations, respectively. Linezolid was well tolerated. In 76 (39.8%) of the 191 episodes of infection, patients experienced one or more adverse events or exhibited one or more abnormal laboratory results; in 35 (18.3%) of the 191 cases it was necessary to discontinue treatment. Gastrointestinal tract-related symptoms (nausea, vomiting and diarrhoea) were the most common possibly or probably related adverse events and the most common reasons for drug discontinuation. CONCLUSIONS: Linezolid was effective and well tolerated in patients with S. aureus infections who were enrolled in this compassionate use protocol.

Acetamides↗

Linezolid for the treatment of methicillin-resistant Staphylococcus aureus infections in children.

BACKGROUND: Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are becoming increasingly prevalent. Linezolid is effective and well-tolerated in the treatment of adults with MRSA infections. OBJECTIVE: To evaluate the clinical efficacy and safety of iv/oral linezolid in children with MRSA infections. METHODS: Data were obtained from two independent clinical trials. In an outpatient trial children (5 to 17 years of age) with uncomplicated skin and skin structure infections (SSSIs) were treated with linezolid or cefadroxil. In an inpatient trial hospitalized children (0 to 11 years of age) with pneumonia, bacteremia or complicated SSSI caused by resistant Gram-positive pathogens were administered iv linezolid with the option to switch to oral suspension (patients >90 days of age) or iv vancomycin. A subset of patients with MRSA infections from the two clinical trials is analyzed herein. RESULTS: In the outpatient trial children with skin infections caused by MRSA were treated with linezolid (15 patients) and cefadroxil (10 patients). In the microbiologically evaluable population, the clinical cure rate was 92.3% in the linezolid group and 85.7% in the cefadroxil group (P = 0.64). The pathogen eradication rate for MRSA was 92.3 and 85.7% in the linezolid and cefadroxil groups, respectively (P = 0.64). There were very few adverse events or drug-related adverse events and no serious adverse events in the outpatient trial. In the inpatient trial 20 children treated with linezolid and 14 treated with vancomycin had infections caused by MRSA. In the microbiologically evaluable population, the clinical cure rate was 94.1% in the linezolid group and 90.0% in the vancomycin group (P = 0.69). Pathogen eradication rates were 88.2 and 90.0% for the linezolid and vancomycin groups, respectively (P = 0.89). Susceptibility patterns of the MRSA isolates showed distinct patterns between the outpatient and inpatient trials. In the inpatient trial fewer patients in the linezolid group had drug-related adverse events than did those in the vancomycin group (20% vs. 43%; P = 0.15). CONCLUSIONS: Intravenous/oral linezolid is effective and well-tolerated in children with MRSA infections.

Acetamides↗

Methicillin-resistant Staphylococcus aureus infection in palliative care.

Our objective was to assess the impact of methicillin-resistant Staphylococcus aureus (MRSA) infection in palliative care. The study was conducted at three hospices in south London, totalling 118 beds, and the following two methods were used. Firstly, a retrospective review of the notes of patients who were known to be MRSA positive at admission or were subsequently found to be MRSA positive was taken. Secondly, a prospective study of factors influencing bed occupancy in one hospice was conducted. The proportion of admissions who were MRSA positive ranged from 4% to 8% in the three hospices. Seven of the 43 patients who had MRSA suffered clinically significant infections. Risk factors for colonization and bacteraemia were similar to the general population. Sites of infection were variable and multiple and treatment regimes for eradication were variable, with varying outcomes. MRSA infection appeared to delay admission because of the need for single rooms, of which there are few Time spent cleaning rooms after discharge or death also reduced the number of available beds. It was concluded that MRSA infection is associated with significant morbidity in a small number of palliative care patients. Beds unavailable because of MRSA should be considered in bed occupancy figures, otherwise bed occupancy may appear artificially low. The psychological and financial impact of the infection in palliative care patients needs further evaluation.

Adult↗

Generalized lymphadenopathy in continuous ambulatory peritoneal dialysis patients associated with Staphylococcus epidermidis infection.

In patients utilizing continuous ambulatory peritoneal dialysis (CAPD), Staphylococcus epidermidis is the most prevalent organism isolated from peritoneal and exit site infections [1] although clinically significant systemic infection is unusual. We report 2 patients undergoing CAPD who developed generalized lymphadenopathy following peritonitis and exit site infection with S. epidermidis isolated from the excised lymph nodes. We conclude that catheter-related S. epidermidis infection may result in generalized lymphadenopathy due to dissemination of the infective focus.

Adult↗

[Serological diagnosis of Staphylococcus aureus infections using anti-A beta teichoic acid antibodies assay (author's transl)].

225 control subjects, 12 hospitalized Staphylococcus free (34 sera) and 16 S. aureus infected patients (79 sera) were tested for anti-A beta teichoic acid antibodies, using counter-immunoelectrophoresis. Anti-alpha and gamma haemolysins antibodies were dosed in parallel in 164 sera. Less than 5 per cent of control sera (3,11 per cent) have an antibody tire higher than 1/8: this tire is therefore selected as threshold level of positivity. Ten of the 12 hospitalized patients without staphylococcal infections are below this level. 31,6 per cent of staphylococcus infected patients have higher serum titers; only 3,7 per cent have no antibodies. In the others, a significant rise in titres is observed. There is no correlation between anti-alpha and gamma staphylolysin and anti-teichoic acid antibodies titres. The method suggested, both easy and rapid, could be used in association with anti-staphylolysin dosage for serological diagnosis of staphylococcal infections.

Antibodies, Bacterial↗

Comparison of a new enzyme-linked immunosorbent assay method with counterimmunoelectrophoresis for detection of teichoic acid antibodies in sera from patients with Staphylococcus aureus infections.

Ribitol-teichoic acid antibodies were measured by a new enzyme-linked immunosorbent assay (ELISA) and by counterimmunoelectrophoresis in serum samples from 47 patients with serious Staphylococcus aureus infections, 63 infected patients, and 177 healthy controls. The same antigen was used for both tests. The group of patients with S. aureus endocarditis (6 patients) had significantly higher ELISA readings than the patients with other deep-seated infections (26 patients) or with an uncomplicated S. aureus bacteremia (15 patients). The patients with other serious gram-positive (40 patients) or gram-negative (23 patients) infections did not differ from the healthy control group. There were only three (7.5%) low-level cross-reactions among the infections caused by gram-positive organisms other than S. aureus. Of 46 initially ribitol-teichoic acid antibody-negative patients followed up for 2 weeks or more, only those developing a serious S. aureus infection showed a significant rise of the ELISA reading. There was a good correlation between ELISA and counterimmunoelectrophoresis. Both tests could be useful in the diagnosis and the management of complicated S. aureus infections. The ELISA method is, however, more sensitive and usually reflects the antibody rise after an infection earlier than does counterimmunoelectrophoresis.

Antibodies, Bacterial↗

Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections.

BACKGROUND: Patients with nasal carriage of Staphylococcus aureus have an increased risk of surgical-site infections caused by that organism. Treatment with mupirocin ointment can reduce the rate of nasal carriage and may prevent postoperative S. aureus infections. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to determine whether intranasal treatment with mupirocin reduces the rate of S. aureus infections at surgical sites and prevents other nosocomial infections. RESULTS: Of 4030 enrolled patients who underwent general, gynecologic, neurologic, or cardiothoracic surgery, 3864 were included in the intention-to-treat analysis. Overall, 2.3 percent of mupirocin recipients and 2.4 percent of placebo recipients had S. aureus infections at surgical sites. Of the 891 patients (23.1 percent of the 3864 who completed the study) who had S. aureus in their anterior nares, 444 received mupirocin and 447 received placebo. Among the patients with nasal carriage of S. aureus, 4.0 percent of those who received mupirocin had nosocomial S. aureus infections, as compared with 7.7 percent of those who received placebo (odds ratio for infection, 0.49; 95 percent confidence interval, 0.25 to 0.92; P=0.02). CONCLUSIONS: Prophylactic intranasal application of mupirocin did not significantly reduce the rate of S. aureus surgical-site infections overall, but it did significantly decrease the rate of all nosocomial S. aureus infections among the patients who were S. aureus carriers.

Administration, Intranasal↗

Methicillin-resistant Staphylococcus aureus infections in correctional facilities---Georgia, California, and Texas, 2001-2003.

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are common in hospitals and nursing homes. Because MRSA is resistant to all commonly prescribed beta-lactam antibiotics (e.g., penicillins and cephalosporins), these infections require treatment with alternative antimicrobial drugs. In addition, because antimicrobial drugs usually must be selected before identifying MRSA as the cause of infection, treatment presents a challenge for clinicians. MRSA has emerged recently as a more frequent cause of skin and soft tissue infections in the community, particularly in correctional facilities such as prisons, jails, and detention centers. This report summarizes recent investigations of MRSA transmission among inmates of correctional facilities in Georgia, California, and Texas. Inadequate personal hygiene, barriers to medical care, and other factors contributed to transmission. Information from these investigations has been used in the development of recently released Federal Bureau of Prisons guidance for control of MRSA, which recommends improvements in inmate hygiene, infection control, and targeted antimicrobial treatment.

California↗

Teicoplanin compared with vancomycin in methicillin-resistant Staphylococcus aureus infections: preliminary results.

Twenty-one patients were included in an open randomized study comparing vancomycin 1 g bd with teicoplanin 400 mg daily in severe methicillin-resistant Staphylococcus aureus infections. The median duration of therapy was 15 days for vancomycin and 21 days for teicoplanin. Most patients presented with severe underlying conditions, such as major surgery (8), solid tumours (5), multiple trauma (3). The infections treated, included septicaemia, osteomyelitis, bronchopneumonia, cellulitis and acute pyelonephritis. Mean MICs of the strains were 0.39 mg/l for vancomycin and 0.195 mg/l for teicoplanin. Mean trough and peak serum concentrations of vancomycin were 14.3 +/- 5 mg/l and 34.3 +/- 13 mg/l, while the teicoplanin values were 7.5 +/- 4 mg/l and 17 +/- 7 mg/l. The cure rate was seven of 12 in the teicoplanin group and six of nine in the vancomycin group, with four and three cases, respectively, of improvement and one failure in the teicoplanin group. Transient renal impairment occurred in two cases with both regimens; superinfection and colonization in three patients and one patient, respectively, with both regimens.

Adult↗

Vascular prosthetic infection with Staphylococcus epidermidis: experimental study of pathogenesis and therapy.

To determine whether a slime-producing strain of Staphylococcus epidermidis was capable of producing acute infection of a prosthetic vascular graft, 5 cm segments of knitted Dacron were implanted in the infrarenal aortic position of dogs in three groups of animals. These included a control group (no graft contamination), a contaminated group that received a graft soaked in an S. epidermidis solution (untreated group), and a contaminated group in which perioperative antibiotics (three doses of cefamandole, 100 mg/kg) were administered (prophylaxis group). In all the animals reexploration and graft removal were performed at 10 days, with replacement of the defect being achieved with a new uncontaminated graft. These animals underwent exploration a third time after an additional 10-day period. S. epidermidis was not grown from the control animals (n = 7) but was cultured in 44% of the prophylaxis group (n = 9) and 88% of the untreated group (n = 16) during at least one of the operative procedures (chi 2 = 15.859; p less than 0.001). The pathologic features of acute S. epidermidis infection were best seen in the untreated animals and included anastomotic disruption (56%), periaortic hematoma, and lymphadenopathy (94%). Microscopic examination of the aortic tissues revealed extensive infiltrates of leukocytes, macrophages, and foreign body giant cells with aortic necrosis. These features were less prominent in the prophylaxis animals. We conclude that S. epidermidis is capable of producing acute graft infection with perigraft inflammation and anastomotic disruption. The administration of perioperative antibiotics reduced but did not abolish these effects of bacterial contamination of prosthetic vascular grafts.

Animals↗

Eradication of endemic methicillin-resistant Staphylococcus aureus infections from a neonatal intensive care unit.

To control infections with endemic methicillin-resistant Staphylococcus aureus (MRSA) in a neonatal intensive care unit (NICU), triple dye was applied to the umbilical cords of infants in the intermediate-care but not the intensive-care area. The rate of MRSA infection, adjusted for time and intensity of care, decreased in the intermediate-care area (rate ratio, 0.35; 95% confidence interval [CI], 0.14-0.87; P < .01) but not in the intensive-care area (rate ratio, 0.92; 95% CI, 0.41-2.24; P = .48). After 22 months, the rate increased in both areas (Mantel-Haenszel rate ratio, 1.7; 95% CI, 1.0-2.8; P < .05) after overcrowding and understaffing increased. After temporary reduction of overcrowding and understaffing, extension of triple dye use to the intensive-care area and dedication of an infection control nurse to the NICU, MRSA colonization and infection rates decreased to near zero in both areas (infection rate ratios, 0.09 and 0.11, respectively; P < .005). The endemic MRSA strain, identified by pulsed-field gel electrophoresis, was eradicated.

Birth Weight↗

Efficacy of intramammary tilmicosin and risk factors for cure of Staphylococcus aureus infection in the dry period.

The objective ofthis study was to evaluate the efficacy of intramammary tilmicosin, administered at drying-off, for eliminating Staphylococcus aureus infection, and to identify risk factors for S. aureus cure during the dry period. A total of 219 naturally infected cows, representing 308 quarters, were randomized to receive either one of two treatments at drying-off. Cows received either an intramammary infusion of 500 mg of benzathine cloxacillin, or a sterile solution containing 1,500 mg of tilmicosin. All cows had quarter milk samples taken aseptically three times before dry-off, and at wk 1, 2, and 4 of the subsequent lactation. Overall, 62% of cows and 67.5% of quarters infected with S. aureus cured during the dry period. The cure following administraton of tilmicosin was 67.3 and 72.5% for cows and quarters, respectively. By comparison, the cure achieved with cloxacillin was 56.9 and 62.9% of cows and quarters. Cows receiving tilmicosin were 2.1 times more likely to cure. The cure rate for cows decreased as the linear score on the last DHI test increased, and as the amount of S. aureus being shed increased. Quarters that cultured positive multiple times before drying-off were less likely to cure. Staphylococcus aureus infections located in front quarters of the udder were 2 times more likely to cure than those in hind quarters. Results of this study demonstrate that intramammary tilmicosin at drying-off is efficacious in curing existing S. aureus during the dry period. Risk factors associated with the cure of S. aureus were identified.

Animals↗

Five cases of bacterial endocarditis after furunculosis and the ongoing saga of community-acquired methicillin-resistant Staphylococcus aureus infections.

Bacterial endocarditis secondary to Panton-Valentine leukocidin producing community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections is rare. We report 5 previously healthy patients who presented with endocarditis after developing furunculosis due to CA-MRSA. A retrospective chart review of all patients with MRSA positive blood cultures was conducted over a 12-month period. Patients with multiple positive blood cultures within 72 h of admission and who had no risk factors for MRSA acquisition were included. Modified Duke's criteria were used to define bacterial endocarditis. PCR detection of Panton-Valentine leukocidin (PVL) genes as well as SCCmec typing was performed. In addition, strain typing of MRSA isolates was performed utilizing pulsed-field gel electrophoresis. Five out of a total of 193 patients had features consistent with CA-MRSA infections and met modified Duke's criteria for bacterial endocarditis. Blood culture isolates were found to be PVL gene positive and carried the type IV SCCmec element. PFGE confirmed that skin isolate was identical to the isolate cultured from his blood. Bacterial endocarditis in patients with CA-MRSA furunculosis is an emerging entity. In areas where CA-MRSA skin infections are prevalent, inappropriate initial antibiotics remain a major problem and may result in significant morbidity.

Adult↗

Treatment approaches for community-acquired methicillin-resistant Staphylococcus aureus infections.

PURPOSE OF REVIEW: This review addresses therapeutic approaches to community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections, focusing on recently published data in the English-language medical literature dating from June 2004 to July 2005. RECENT FINDINGS: During the reviewed time period, the overall understanding of the epidemiology and virulence of community-acquired MRSA has continued to advance. This same period has also seen numerous works dealing with the newer and emerging anti-staphylococcal antimicrobial agents. Important clinical trials involving linezolid, daptomycin, tigecycline, dalbavancin, and telavancin have been completed. At the same time, owing to the cost of newer agents and the broad susceptibility pattern of community-acquired MRSA, many older antimicrobial agents (long-acting tetracyclines, fluoroquinolones, rifampin, trimethoprim-sulfamethoxazole, and clindamycin) have also been reexamined. SUMMARY: As data accumulates, the newer antimicrobial agents active against community-acquired MRSA continue to demonstrate their value. Despite the appeal and abundant publications involving newer agents, older antimicrobials certainly retain a therapeutic role. Considerable work needs to be done prospectively evaluating older agents for community-acquired MRSA disease. The most important therapeutic intervention for the majority of community-acquired MRSA infections is adequate drainage of purulent fluid collections. Antimicrobial selection for community-acquired MRSA infections should be governed by disease severity, susceptibility patterns (especially based on timely clinical specimen culture), clinical response to therapy, and cost.

Acetamides↗

Use of pulsed-field gel electrophoresis in the analysis of recurrent Staphylococcus aureus infections in patients on continuous ambulatory peritoneal dialysis.

BACKGROUND/AIM: The purpose of this study was to evaluate pulsed-field gel electrophoresis (PFGE) for distinguishing between relapse and reinfection of Staphylococcus aureus infections in patients on continuous ambulatory peritoneal dialysis (CAPD). METHODS: Between July 1993 and May 1997, 4 patients with recurrent CAPD-associated infections caused by S. aureus we enrolled in this study. There were nine episodes of peritonitis, one episode of temporary double lumen catheter infection, and one episode of Hickman catheter infection. A total of eleven S. aureus isolates were collected from peritoneal fluid (n = 9) and blood (n = 2). PFGE typing was applied. RESULTS: In our study, from PFGE typing, the 11 S. aureus isolates were classified into seven patterns. Antibiogram profiling classified only four patterns. Patient A had a reinfection by another strain of S. aureus, and patient B had three episodes of peritonitis caused by the same strain of S. aureus due to exit site infections. Patient C had two episodes of CAPD peritonitis caused by two different strains, respectively. Patient D had four episodes of S. aureus infection (three CAPD peritonitis and one bacteremia); the first two episodes of peritonitis were caused by an identical strain of S. aureus, whereas the subsequent two infections were caused by other organisms. CONCLUSION: PFGE has a high discriminatory power and can be an assistant method to antibiogram profiling for distinguishing relapse from reinfection in CAPD-associated peritonitis.

Anti-Bacterial Agents↗

Treatment of methicillin-resistant staphylococcus aureus infections with quinupristin-dalfopristin in patients intolerant of or failing prior therapy. For the Synercid Emergency-Use Study Group.

Safety and efficacy of quinupristin-dalfopristin (an injectable streptogramin antibiotic) were evaluated in the treatment of a variety of infections due to methicillin-resistant Staphylococcus aureus (MRSA) in patients either intolerant of or failing prior therapy. The influence of resistance phenotypes on treatment outcome was also assessed. This worldwide, multicentre, open-label, non-comparative, emergency-use clinical study enrolled patients with one or more of nine predefined, culture-confirmed infections with MRSA, who had no clinically appropriate alternative antibiotic therapy. The recommended quinupristin-dalfopristin dose was 7.5 mg/kg administered iv every 8 h for a duration judged appropriate by the investigator. There were no restrictions on prior or concomitant treatment with other antibiotics. Clinical, microbiological and laboratory assessments were performed at baseline, during study drug treatment, within 24 h after the last dose, and 7-21 days post-therapy. Ninety patients [age (mean +/- S.D.) 57.4 +/- 18.5 years] with significant underlying medical illnesses were treated at 63 centres in five countries. The most common indications were bone and joint infection (44.4% of patients) and skin and skin structure infection (16.7%). The mean (+/- S.D.) daily dose and treatment duration was 20.2 +/- 2.9 mg/kg/day for 28.5 +/- 22.3 days, most frequently administered every 8 h. The overall success rate (defined as a clinical outcome of either cure or improvement and a bacteriological outcome of eradication or presumed eradication) was 71.1% in the all-treated population (n = 90) and 66.7% in patients who were both clinically and bacteriologically evaluable (n = 27). Success rates for endocarditis, respiratory tract infection and bacteraemia of unknown source were below the population mean. The macrolide-lincosamide-streptogramin type B resistance phenotype did not appear to alter the response rate. The most common non-venous adverse events related to study medication were arthralgias (10.8%), myalgias (8.6%) and nausea (8.6%). Quinupristin-dalfopristin should be considered as a treatment option for infections caused by MRSA, especially in patients intolerant of or failing alternate therapy.

Adolescent↗

Use of cefazolin microspheres to treat localized methicillin-resistant Staphylococcus aureus infections in rats.

BACKGROUND: In a previous study, the topical administration of biodegradable, controlled-release poly-(dl-lactide-co-glycolide) cefazolin microspheres could effectively prevent surgical wound infections with a sensitive strain of Staphylococcus aureus in an experimental animal model. The objective of the current study was to evaluate and compare the efficacy of topical antibiotic therapy with cefazolin microspheres to systemic cefazolin therapy for the treatment of experimental rat surgical wounds contaminated with a methicillin-resistant strain of S. aureus (MRSA). METHODS: A local infection model in rats was used. MRSA was used to infect pockets surgically produced in the paraspinous muscles. Groups of rats received either topical cefazolin microspheres, topical cefazolin powder, parenteral cefazolin, or no treatment. Feces were cultured to evaluate the effect of antibiotic therapy on gut flora. RESULTS: The rate of clinical wound infection following topical application of cefazolin microspheres (13%) was significantly lower than the 53% infection rate observed in rats who had received a 2-week course of systemic cefazolin therapy (P = 0.046). Moreover, single-dose topical antibiotic therapy with cefazolin microspheres completely eradicated MRSA from the wounds of 7 of 15 (47%) animals. There was no statistically significant difference, however, in the rate of clinical wound infection between rats whose wounds were treated topically with free cefazolin powder and those treated with systemic cefazolin (P = 0.12). Importantly, selection of antibiotic-resistant bacteria was associated with systemic but not local cefazolin therapy. CONCLUSION: The results of this study suggest that topical antibiotic therapy with controlled-release cefazolin microspheres may be effective for the prevention of wound infection with both methicillin-sensitive and methicillin-resistant strains of S. aureus in selected surgical procedures that are at high risk of developing postoperative wound infection.

Administration, Topical↗