Contact precautions: more is not necessarily better.

OBJECTIVE: To determine whether increases in contact isolation precautions are associated with decreased adherence to isolation practices among healthcare workers (HCWs). DESIGN: Prospective cohort study from February 2009 to October 2009. SETTING: Eleven teaching hospitals. PARTICIPANTS: HCWs. METHODS: One thousand thirteen observations conducted on HCWs. Additional data included the number of persons in isolation, types of HCWs, and hospital-specific contact precaution practices. Main outcome measures included compliance with individual components of contact isolation precautions (hand hygiene before and after patient encounter, donning of gown and glove upon entering a patient room, and doffing upon exiting) and overall compliance (all 5 measures together) during varying burdens of isolation. RESULTS: Compliance with hand hygiene was as follows: prior to donning gowns/gloves, 37.2%; gowning, 74.3%; gloving, 80.1%; doffing of gowns/gloves, 80.1%; after gown/glove removal, 61%. Compliance with all components was 28.9%. As the burden of isolation increased (20% or less to greater than 60%), a decrease in compliance with hand hygiene (43.6%-4.9%) and with all 5 components (31.5%-6.5%) was observed. In multivariable analysis, there was an increase in noncompliance with all 5 components of the contact isolation precautions bundle (odds ratio [OR], 6.6 [95% confidence interval (CI), 1.15-37.44]; P = .03) and in noncompliance with hand hygiene prior to donning gowns and gloves (OR, 10.1 [95% CI, 1.84-55.54]; P = .008) associated with increasing burden of isolation. CONCLUSIONS: As the proportion of patients in contact isolation increases, compliance with contact isolation precautions decreases. Placing 40% of patients under contact precautions represents a tipping point for noncompliance with contact isolation precautions measures.

Staphylococcus aureus skin/soft-tissue infections: the impact of SCCmec type and Panton-Valentine leukocidin.

We assessed the role of Panton-Valentine leukocidin (PVL) and SCCmec type in community associated (CA) and healthcare associated (HC) Staphylococcus aureus (SA) skin/soft-tissue infections (STI). We prospectively monitored microbiology results (11 January 2005 to 6 January 2006), screened inpatients with SA in tissue samples or blood, and selected adults with STI. We recorded clinical/microbiological characteristics, and tested saved isolates for PVL genes (real time PCR) and SCCmec type (conventional multiplex PCR). We encountered 204 patients. MRSA strains that accounted for 70.5% CA and 66.0% HC cases, caused more abscesses (55.7% vs 29.7%; p =0.001) and were often PVL-positive (68.9% vs 4.8%; p <0.001). PVL-positive isolates caused more abscesses (72.9% vs 26.5%; p <0.001) but similar bacteremia (7.3% vs 7.1%). SCCmec IVa made up 95.8% of PVL-positive strains and accounted for 69.8% of the abscesses. SCCmec II caused higher mortality (14.8% vs 0-3.1%; p = 0.02). PVL was a predictor of abscesses (p <0.001). Predictors of bacteremia were age > or = 65 y (p =0.004), necrotizing infection (p =0.014), and head/neck location (p =0.05). These findings suggest that SCCmec type and PVL status influence STI manifestations and contribute to MRSA-MSSA differences. PVL is implicated in abscess formation but not bacteremia. Bacteremia is likely related to host condition and/or other virulence factors that were not studied.

Long-term immunologic and virologic responses in patients with highly resistant HIV infection who are treated with an incompletely suppressive antiretroviral regimen.

BACKGROUND: Some treatment-experienced patients with highly drug-resistant human immunodeficiency virus (HIV) infection have no option but to continue to receive an incompletely suppressive regimen (ISR). We performed a study to determine their long-term immunologic and virologic responses to ISR, to investigate risks for immunologic or virologic failure, and to examine for the occurrence of new drug-resistance mutations. METHODS: Antiretroviral treatment-experienced HIV-infected patients with a genotype sensitivity score < or = 1, an HIV load > 1000 copies/mL, and no available optimized regimen were included in the study. The proportion of patients treated with ISR who developed immunologic failure (defined as a 25% reduction in the CD4 cell count from the baseline level) and virologic failure (defined as a > or = 0.5-log10 increase in the HIV load from the baseline level) was determined. Cox proportional hazards analysis was used to investigate variables associated with immunologic or virologic failure. New drug-resistant mutations were calculated in 27 patients with sequential genotypes available. RESULTS: Forty-seven patients (median duration of prior antiretroviral therapy, 89 months; median CD4 cell count, 277 cells/mm3; and median HIV load, 19,728 copies/mL) had multiple HIV mutations (a median of 5 nucleoside reverse-transcriptase inhibitor mutations, 1 nonnucleoside reverse-transcriptase inhibitor mutation, and 6 protease inhibitor mutations; median genotype sensitivity score, 0) at baseline. By 48 months after ISR use, 43% had developed immunologic failure, and 22% had developed virologic failure. None of the studied variables (i.e., age, < 50 years; baseline HIV load, > 100,000 copies/mL; baseline CD4 cell count, < 200 cells/mm3; or inclusion of lamivudine in the treatment regimen) were associated with immunologic or virologic failure. New nucleoside reverse-transcriptase inhibitor mutations occurred in 63% of patients, and new primary protease inhibitor mutations occurred in 52.6% of protease inhibitor recipients. No deaths occurred. A total of 8.5% of patients experienced a new AIDS-defining event. CONCLUSIONS: Most patients with highly drug-resistant HIV infection who were treated with an ISR maintain durable immunologic and virologic responses. New drug-resistant mutations occur frequently.

Reviews of anti-infective agents: posaconazole: a broad-spectrum triazole antifungal agent.

Posaconazole is a triazole antifungal agent with a spectrum of activity that includes Candida and Cryptococcus species, many molds, and some endemic fungi. Posaconazole has received US Food and Drug Administration approval for the treatment of oropharyngeal candidiasis, including infections refractory to itraconazole and/or fluconazole. It is also approved as prophylaxis for invasive Aspergillus and Candida infections in patients aged >or=13 years who are at high risk of developing these infections, in adult and adolescent hematopoietic stem cell transplant recipients with graft-versus-host disease, and in persons with hematologic malignancies and prolonged neutropenia due to chemotherapy, who are at high risk of developing these infections. Approval for additional indications is being sought. Limited clinical experience suggests efficacy for the treatment of infections due to Zygomycetes and as salvage therapy for patients with invasive aspergillosis and coccidioidomycosis. Currently available only as an oral suspension, posaconazole, which has been well tolerated, requires administration with food or a nutritional supplement to assure adequate bioavailability. Posaconazole is predominantly eliminated in the feces, where it appears as unchanged drug. Metabolism, mostly glucuronidation, plays only a minor role in its elimination, as does renal clearance; as a consequence, dose adjustment is not required in the presence of renal or hepatic insufficiency. Although not a substrate of hepatic CYP450 3A4, posaconazole inhibits this enzyme and thus has the potential for significant pharmacokinetic interactions with drugs metabolized by this isoform. Its use in combination with CYP450 substrates that prolong the QTc interval is contraindicated, as is its use with ergot alkaloids; administration of posaconazole with other substrates and/or inducers of this enzyme system requires caution. Posaconazole is both a substrate and inhibitor of P-glycoprotein. Currently, the major roles for posaconazole in clinical practice are as prophylaxis for neutropenic patients with significant risk of infection with filamentous fungi and as therapy for zygomycoses. It may also have a role in the treatment of other filamentous fungal and some yeast infections, but assessment of its overall place in antifungal therapy awaits the availability of further clinical experience.

Bacterial infections in adult HIV-infected patients.

PURPOSE: The purpose of this article is to critically review articles published from the pre-HAART era to the present on bacterial infections in adult HIV-infected patients. METHOD: Literature search on bacterial infections in HIV-infected patients yields predominantly small case series from single centers, many of which are retrospectively collected. RESULTS: Variations in case selection limit the utility of these articles for assessing the epidemiology and clinical features of a particular infection. Nonetheless, numerous articles indicate that certain bacterial infections occur most often when CD4 cell counts are < 200/mm3. In the pre-HAART era, others suggest that PcP prophylaxis with TMP/SMX and MAC prophylaxis with macrolides reduced rates of several bacterial infections. Since the advent of HAART, however, some articles suggest that the incidence of various infections has declined and that withdrawal of OI prophylaxis in patients who have had HAART restoration of CD4 cell counts has not led to an increase in certain bacterial infections. CONCLUSION: This review suggests that bacterial infections may have declined in the HAART era, as multicenter cohort studies have shown to be the case with AIDS-associated OIs. Nonetheless, preventive measures such as pneumococcal vaccination and smoking cessation remain effective strategies.