Impact of an antimicrobial utilization program on antimicrobial use at a large teaching hospital: a randomized controlled trial.

BACKGROUND: Multidisciplinary antimicrobial utilization teams (AUTs) have been proposed as a mechanism for improving antimicrobial use, but data on their efficacy remain limited. OBJECTIVE: To determine the impact of an AUT on antimicrobial use at a teaching hospital. DESIGN: Randomized controlled intervention trial. SETTING: A 953-bed, public, university-affiliated, urban teaching hospital. PATIENTS: Patients who were given selected antimicrobial agents (piperacillin-tazobactam, levofloxacin, or vancomycin) by internal medicine ward teams. INTERVENTION: Twelve internal medicine teams were randomly assigned monthly: 6 teams to an intervention group (academic detailing by the AUT) and 6 teams to a control group that was given indication-based guidelines for prescription of broad-spectrum antimicrobials (standard of care), during a 10-month study period. MEASUREMENTS: Proportion of appropriate empirical, definitive (therapeutic), and end (overall) antimicrobial usage. RESULTS: A total of 784 new prescriptions of piperacillin-tazobactam, levofloxacin, and vancomycin were reviewed. The proportion of antimicrobial prescriptions written by the intervention teams that was considered to be appropriate was significantly higher than the proportion of antimicrobial prescriptions written by the control teams that was considered to be appropriate: 82% versus 73% for empirical (risk ratio [RR], 1.14; 95% confidence interval [CI], 1.04-1.24), 82% versus 43% for definitive (RR, 1.89; 95% CI, 1.53-2.33), and 94% versus 70% for end antimicrobial usage (RR, 1.34; 95% CI, 1.25-1.43). In multivariate analysis, teams that received feedback from the AUT alone (adjusted RR, 1.37; 95% CI, 1.27-1.48) or from both the AUT and the infectious diseases consultation service (adjusted RR, 2.28; 95% CI, 1.64-3.19) were significantly more likely to prescribe end antimicrobial usage appropriately, compared with control teams. CONCLUSIONS: A multidisciplinary AUT that provides feedback to prescribing physicians was an effective method in improving antimicrobial use. Trial registration. ClinicalTrials.gov identifier: NCT00552838.

Polymyxin B and doxycycline use in patients with multidrug-resistant Acinetobacter baumannii infections in the intensive care unit.

BACKGROUND: Multidrug-resistant Acinetobacter baumannii (MDR-Ab) has emerged as an increasingly problematic cause of hospital-acquired infections in the intensive care unit (ICU). MDR-Ab is resistant to most standard antimicrobials but often retains susceptibility to polymyxin B and doxycycline. OBJECTIVE: To evaluate the efficacy and toxicity of polymyxin B and doxycycline in the treatment of MDR-Ab infections. METHODS: A retrospective chart review was conducted between March 2002 and May 2005 in patients who received doxycycline or polymyxin B for treatment of MDR-Ab infections in ICUs within Grady Memorial Hospital, Atlanta, GA. RESULTS: Thirty-seven patients with MDR-Ab infections were treated with polymyxin B or doxycycline. Median age was 41 years and median ICU length of stay was 18 days prior to acquisition of MDR-Ab. Clinical cure was observed in 22 of 29 (76%) evaluable patients treated with polymyxin B and 2 of 4 (50%) patients treated with doxycycline. In patients with follow-up cultures, microbiological cure was observed in 17 of 21 (81%) patients treated with polymyxin B and 2 of 3 (67%) patients treated with doxycycline. Nephrotoxicity developed in 21% (7 of 33) of patients who received polymyxin B. Neurotoxicity was observed in 2 (6%) patients who received polymyxin B. No adverse reactions were observed with doxycycline. Overall, crude mortality was 27% (9 of 33) and 75% (3 of 4) among those who received polymyxin B and doxycycline, respectively. Three (9%) deaths were attributed to polymyxin B treatment failure, and no deaths were attributed to doxycycline treatment failure. CONCLUSIONS: Polymyxin B was effectively used to treat a substantial proportion of critically ill patients with MDR-Ab infection and was associated with a similar rate of nephrotoxicity as previously reported. Doxycycline monotherapy was used in a limited number of patients for the treatment of MDR-Ab; further evaluation of its efficacy in larger numbers of patients is warranted.

Emergence of community-acquired methicillin-resistant Staphylococcus aureus USA 300 clone as the predominant cause of skin and soft-tissue infections.

BACKGROUND: Studies have shown that community-acquired methicillin-resistant Staphylococcus aureus (MRSA) causes S. aureus skin and soft-tissue infection in selected populations. OBJECTIVE: To determine the proportion of infections caused by community-acquired MRSA, the clinical characteristics associated with community-acquired MRSA, and the molecular epidemiology of community-acquired MRSA among persons with community-onset S. aureus skin and soft-tissue infection. DESIGN: Active, prospective laboratory surveillance to identify S. aureus recovered from skin and soft-tissue sources. SETTING: 1000-bed urban hospital and its affiliated outpatient clinics in Atlanta, Georgia. PATIENTS: 384 persons with microbiologically confirmed community-onset S. aureus skin and soft-tissue infection. MEASUREMENTS: Proportion of infections caused by and clinical factors associated with community-acquired MRSA among persons with community-onset S. aureus skin and soft-tissue infection. Pulsed-field gel electrophoresis and antimicrobial susceptibility patterns were used to epidemiologically classify community-onset S. aureus infections. Community-acquired MRSA was defined by MRSA isolates that either demonstrated a USA 300 or USA 400 pulsed-field type or had a susceptibility pattern showing resistance only to beta-lactams and erythromycin (for isolates not available for pulsed-field gel electrophoresis). RESULTS: Community-onset skin and soft-tissue infection due to S. aureus was identified in 389 episodes, with MRSA accounting for 72% (279 of 389 episodes). Among all S. aureus isolates, 63% (244 of 389 isolates) were community-acquired MRSA. Among MRSA isolates, 87% (244 of 279 isolates) were community-acquired MRSA. When analysis was restricted only to MRSA isolates that were available for pulsed-field gel electrophoresis, 91% (159 of 175 isolates) had a pulsed-field type consistent with community-acquired MRSA; of these, 99% (157 of 159 isolates) were the MRSA USA 300 clone. Factors independently associated with community-acquired MRSA infection were black race (prevalence ratio, 1.53 [95% CI, 1.16 to 2.02]), female sex (prevalence ratio, 1.16 [CI, 1.02 to 1.32]), and hospitalization within the previous 12 months (prevalence ratio, 0.80 [CI, 0.66 to 0.97]). Inadequate initial antibiotic therapy was statistically significantly more common among those with community-acquired MRSA (65%) than among those with methicillin-susceptible S. aureus skin and soft-tissue infection (1%). LIMITATIONS: Some MRSA isolates were not available for molecular typing. CONCLUSIONS: The community-acquired MRSA USA 300 clone was the predominant cause of community-onset S. aureus skin and soft-tissue infection. Empirical use of agents active against community-acquired MRSA is warranted for patients presenting with serious skin and soft-tissue infections.

Emergence of community-associated methicillin-resistant Staphylococcus aureus USA300 genotype as a major cause of health care-associated blood stream infections.

BACKGROUND: Whether community-associated methicillin-resistant Staphylococcus aureus (MRSA) genotypes (e.g., USA300) are a major cause of bloodstream infections (BSIs) and health care-associated infections has been poorly defined. METHODS: Consecutive MRSA isolates recovered from patients with BSIs were prospectively collected at an urban public hospital. Molecular typing studies were performed. Prevalence and risk factors for the MRSA USA300 genotype were assessed. RESULTS: One hundred thirty-two cases of MRSA BSI were documented over 7.5 months in 2004 (incidence, 6.79 per 1000 admissions); 116 isolates were available for genotyping. Characteristics of the 116 evaluable cases included: a mean age 47 years; 62% were male, 82% were African American, and 22% were HIV seropositive. The crude in-hospital mortality rate was 22%. In 107 cases (92%), there was contact with a health care facility within the year prior to infection, and a nosocomial infection (defined as positive blood culture results obtained >48 h after admission) occurred in 49 cases (42%). PFGE demonstrated that 39 (34%) of the 116 isolates were the MRSA USA300 genotype; 34 (29%) were USA100; 42 (36%) were USA500; and 1 (1%) was USA800. MRSA USA300 accounted for 28% of health care-associated BSIs and 20% of nosocomial MRSA BSIs. In multivariate analysis, isolation of the USA300 genotype was associated with injectiondrug use (OR, 3.67; 95% CI, 1.10-12.28) and skin and soft tissue infection (OR, 4.26; 95% CI, 1.08-16.84). Patients who resided in long-term care facilities (OR, 0.09; 95% CI, 0.01-0.82) and those who were treated with antimicrobials in the prior year were less likely to have MRSA USA300 genotype recovered (OR, 0.10; 95% CI, 0.02-0.49). CONCLUSIONS: MRSA USA300 genotype, the predominant cause of community-associated MRSA infections in our area (Atlanta, GA), has now emerged as a significant cause of health care-associated and nosocomial BSI. MRSA USA300 as a nosocomial pathogen presents new challenges to infection control programs.

Emergence of community-associated methicillin-resistant Staphylococcus aureus USA 300 clone as a cause of health care-associated infections among patients with prosthetic joint infections.

BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as an important cause of staphylococcal infections, but there have been little data on whether CA-MRSA causes health care-associated infections. METHODS: A case-control study was performed to identify risk factors for prosthetic joint infections (PJI). Antibiograms of isolates associated with PJI were reviewed. Molecular typing of available MRSA isolates was done using pulsed field gel electrophoresis (PFGE). Nares cultures of health care workers who provided care to those orthopedic patients were obtained. RESULTS: Over a 13-month period (January 2003-January 2004), 9.5% of patients with prosthetic hip (THA) or knee (TKA) joint surgery developed PJI (7 TKA and 2 THA). The mean time to development of PJI was 20 days. Five infections were caused by CA-MRSA and 3 by methicillin-susceptible S aureus; one was culture negative. All CA-MRSA isolates had identical antibiograms (resistant to beta-lactams and erythromycin; susceptible to clindamycin, trimethoprim-sulfamethoxazole, rifampin, gentamicin, levofloxacin, and vancomycin). Molecular typing of 2 available CA-MRSA isolates revealed that these were the USA300 clone; these isolates were PVL+ and carried SCCmec IV. CA-MRSA was not recovered from nares cultures from 31 health care workers. In multivariate analysis, TKA (OR, 8.1; 95% CI: 1.3-48.1) and surgery time >180 minutes (OR, 7.4; 95% CI: 1.4-39.6) were associated with PJI. CONCLUSION: We have demonstrated that the CA-MRSA USA300 clone is no longer just a cause of community-acquired infections but has also emerged as a cause of health care-associated infections, causing PJI at our institution.

Risk factors for colonization with methicillin-resistant Staphylococcus aureus (MRSA) in patients admitted to an urban hospital: emergence of community-associated MRSA nasal carriage.

BACKGROUND: Surveillance cultures performed at hospital admission have been recommended to identify patients colonized with methicillin-resistant Staphylococcus aureus (MRSA) but require substantial resources. We determined the prevalence of and risk factors for MRSA colonization at the time of hospital admission among patients cared for at a public urban hospital. METHODS: Anterior nares cultures were obtained within 48 h after admission during a 1-month period. A case-control study and molecular typing studies were performed. RESULTS: A total of 53 (7.3%) of 726 patients had a nares culture positive for MRSA, and 119 (16.4%) had a nares culture that was positive for methicillin-susceptible S. aureus. In multivariate analysis, risk factors for MRSA colonization included antibiotic use within 3 months before admission (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.2-5.0), hospitalization during the past 12 months (OR, 4.0; 95% CI, 2.0-8.2), diagnosis of skin or soft-tissue infection at admission (OR, 3.4; 95% CI, 1.5-7.9), and HIV infection. A total of 47 (89%) of 53 case patients colonized with MRSA had at least 1 of these independent risk factors, in contrast to 343 (51%) of 673 control patients (OR, 7.5; 95% CI, 3.2 -17.9). Molecular typing demonstrated that 16 (30%) of 53 MRSA nares isolates (2.2% of the 726 isolates) belonged to the USA300 community-associated MRSA (CA-MRSA) genotype. CONCLUSION: The prevalence of MRSA colonization at the time of patient admission was high (>7%). Limiting surveillance cultures to patients with >or=1 of the identified risk factors may allow for targeted screening. The emergence of CA-MRSA colonization represents a new, unrecognized reservoir of MRSA within hospitals, potentially increasing the risk for horizontal transmission.

Dapsone-induced hypersensitivity pneumonitis mimicking Pneumocystis carinii pneumonia in a patient with AIDS.

Interstitial pneumonitis, often related to infectious etiologies, occurs commonly in HIV-infected patients. However, hypersensitivity pneumonitis from noninfectious etiologies, including environmental stimuli or drug exposure, is an unusual etiology of interstitial pneumonitis in HIV-infected patients. We report a patient with AIDS who developed a dapsone-induced hypersensitivity pneumonitis mimicking Pneumocystis carinii (PCP) pneumonia. We believe drug-induced hypersensitivity pneumonitis should be considered in the differential diagnosis of interstitial pneumonia in HIV-infected patients in whom infectious etiologies have been ruled out.

Short-course rifampin and pyrazinamide compared with isoniazid for latent tuberculosis infection: a cost-effectiveness analysis based on a multicenter clinical trial.

Two months of treatment with rifampin-pyrazinamide (RZ) and 9 months of treatment with isoniazid are both recommended for treatment of latent tuberculosis infection in adults without human immunodeficiency virus infection, but the relative cost-effectiveness of these 2 treatments is unknown. We used a Markov model to conduct a cost-effectiveness analysis to assess the impact on life expectancy and costs based on the results of a recent clinical trial that compared the rates of adverse events and completion of the 2 treatment regimens. Compared with no treatment, both regimens increased life expectancy by 1.2 years, but RZ cost 273 dollars more per patient. Sensitivity analyses showed that, assuming equal efficacy between the 2 regimens, there was no threshold completion rate for RZ at which the 2 treatments would be of equal net cost. Under most circumstances, treatment of latent tuberculosis infection with isoniazid is cost-saving than treatment with RZ.

Recurrent invasive pneumococcal disease: a population-based assessment.

We sought to define the risk of recurrence of invasive pneumococcal disease (IPD) and to define the characteristics of persons experiencing recurrent IPD through population-based surveillance. Cases of IPD were identified through the US Centers for Disease Control and Prevention's Active Bacterial Core Surveillance. Recurrent episodes were defined as isolation of Streptococcus pneumoniae from any normally sterile site > or =30 days after initial positive culture. Among 13,924 persons who survived their initial episode of IPD, 318 (2.3%) experienced > or =1 subsequent episode, for 376 total recurrences. The recurrence rate was 1294 episodes per 100,000 person-years, or 50 times the annual incidence of IPD. In multivariable analysis, a higher risk of recurrence was seen in persons infected with human immunodeficiency virus and in children <5 years old with chronic illness. Most (92%) persons with recurrence had a vaccine indication. The risk of recurrence among certain persons with IPD is extremely high.

Short-course rifampin and pyrazinamide compared with isoniazid for latent tuberculosis infection: a multicenter clinical trial.

BACKGROUND: Rifampin and pyrazinamide are recommended for treatment of latent tuberculosis infection in adults without HIV infection, but reports of severe hepatotoxicity have raised concerns about its safety. Clinical trials have not compared this treatment with isoniazid in adults without HIV infection. OBJECTIVE: To compare the safety and tolerance of a 2-month regimen of rifampin and pyrazinamide with that of a 6-month regimen of isoniazid for treatment of latent tuberculosis infection. DESIGN: Multicenter, prospective, open-label trial. SETTING: Three urban public health tuberculosis clinics in the United States. PATIENTS: 589 adults with latent tuberculosis infection who met U.S. criteria for treatment. INTERVENTION: Patients were assigned in alternate weeks to receive rifampin and pyrazinamide daily for 2 months (n = 307) or isoniazid daily for 6 months (n = 282). MEASUREMENTS: Primary end points were hepatotoxicity, other adverse events, and percentage of patients who completed treatment. RESULTS: Sixteen of 207 (7.7%) patients assigned to rifampin and pyrazinamide developed grade 3 or 4 hepatotoxicity compared with 2 of 204 (1%) patients assigned to isoniazid (odds ratio, 8.46 [95% CI, 1.9 to 76.5]; P = 0.001). The rifampin plus pyrazinamide regimen was more likely than the isoniazid regimen to be discontinued because of hepatotoxicity (odds ratio, 5.19; P = 0.033). The overall percentage of nonhepatotoxic adverse events was 20% in the rifampin-pyrazinamide group and 16% in the isoniazid group. The proportion of patients who completed the study treatment was 61% and 57%, respectively. CONCLUSIONS: A 2-month regimen of rifampin and pyrazinamide was associated with an increased risk for grade 3 or 4 hepatotoxicity compared with a 6-month regimen of isoniazid. Liver enzymes should be measured routinely during treatment to screen for liver injury and prevent progression to severe toxicity.

Paradoxical recurrent meningitis following therapy of cryptococcal meningitis: an immune reconstitution syndrome after initiation of highly active antiretroviral therapy.

We report a case of paradoxical recurrent meningitis in response to initiation of highly active antiretroviral therapy in a patient receiving maintenance fluconazole for a previous diagnosis of cryptococcal meningitis. We describe the unusual radiographic and histopathologic findings which are consistent with an immune reconstitution induced paradoxical inflammatory response to residual cryptococcal infection.

Human papillomavirus-associated oral warts among human immunodeficiency virus-seropositive patients in the era of highly active antiretroviral therapy: an emerging infection.

Oral warts are a manifestation of human papillomavirus infection that have been noted infrequently in persons with human immunodeficiency virus (HIV). A nested case-control study was conducted to assess rates of and risk factors for oral warts among a cohort of HIV-seropositive patients. From 1997 through 1999, 56 patients with oral warts were identified among 2194 HIV-positive patients attending an urban oral health center (prevalence, 2.6%). Incident cases of oral warts were significantly more likely to have been diagnosed in 1999 than they were in 1997-1998 (P=.001). Multivariate analysis indicated that the risk of oral warts was associated with a >/=1-log(10) decrease in HIV RNA level in the 6 months before diagnosis of oral warts (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.08-5.11) and with serologic evidence of chronic or previous infection with hepatitis B virus (OR, 2.66; 95% CI, 1.31-5.41). The incidence of oral warts in HIV-seropositive patients appears to be increasing in the era of highly active antiretroviral therapy. Oral warts were associated with reductions in virus load, which suggests that this may in part be related to immune reconstitution.