Outcomes of health care-associated pneumonia empirically treated with guideline-concordant regimens versus community-acquired pneumonia guideline-concordant regimens for patients admitted to acute care wards from home.

BACKGROUND: The introduction of the health care-associated pneumonia (HCAP) categorization expanded recommendations for broad-spectrum empiric antibiotics to pneumonia patients presenting from the community with recent health care-system exposure. However, the efficacy of such regimens in improving clinical outcomes in these patients has not been well established. OBJECTIVE: To compare the clinical outcomes of HCAP patients treated initially with HCAP guideline-concordant antibiotic regimens to those treated initially with community-acquired pneumonia (CAP) guideline-concordant antibiotic regimens. METHODS: This retrospective study included HCAP patients presenting from home and admitted to general medical wards. HCAP regimen patients were treated empirically with at least 1 antipseudomonal agent. All other patients were assigned to the CAP regimen group. The primary end point was clinical cure at 30 days postdischarge. Subgroup analysis was performed in patients hospitalized 1-30 days and 31-90 days before the HCAP admission. RESULTS: Of 228 HCAP admissions, 122 patients received CAP regimens and 106 received HCAP regimens. The 2 groups were similar at baseline, including Pneumonia Severity Index scores. Attributable clinical cure occurred in 75.4% of CAP regimen patients and 69.8% of HCAP regimen patients (p = 0.34). Overall clinical cure occurred in 59.8% of CAP regimen patients and 54.7% of HCAP regimen patients (p = 0.44). The CAP regimen group used fewer days of intravenous antibiotics (4.39 vs 7.75, p < 0.0001) and had shorter lengths of stay (6.36 vs 8.58 days, p < 0.0001). For patients hospitalized 31-90 days earlier, clinical cure was higher in the CAP regimen group (attributable, 82.9% vs 60.0%, p = 0.0090; overall, 67.1% vs 47.5%, p = 0.044). CONCLUSIONS: Compared to CAP guideline-concordant regimens, treatment of HCAP with HCAP guideline-concordant regimens did not increase clinical cure rates and was associated with lower clinical cure rates in patients hospitalized 31-90 days prior to the HCAP admission. This study suggests that broad-spectrum empiric antibiotics may not be necessary in all HCAP patient groups.

Pneumonia in HIV-infected persons: increased risk with cigarette smoking and treatment interruption.

RATIONALE: Bacterial pneumonia is a major cause of morbidity for HIV-infected persons and contributes to excess mortality in this population. OBJECTIVES: To evaluate the frequency and risk factors for occurrence of bacterial pneumonia in the present era of potent antiretroviral therapy. METHODS: We evaluated data from a randomized trial of episodic antiretroviral therapy. The study, Strategies for Management of Antiretroviral Therapy, enrolled 5,472 participants at 318 sites in 33 countries. Study patients had more than 350 CD4 cells at baseline. Diagnosis of bacterial pneumonia was confirmed by a blinded clinical-events committee. MEASUREMENTS AND MAIN RESULTS: During a mean follow-up of 16 months, 116 participants (2.2%) developed at least one episode of bacterial pneumonia. Patients randomized to receive episodic antiretroviral therapy were significantly more likely to develop pneumonia than patients randomized to receive continuous antiretroviral therapy (hazard ratio, 1.55; 95% confidence interval, 1.07-2.25; P = 0.02). Cigarette smoking was a major risk factor: Current-smokers had more than an 80% higher risk of pneumonia compared with never-smokers (hazard ratio, 1.82; 95% confidence interval, 1.09-3.04; P = 0.02). Participants who were on continuous HIV treatment and were current smokers were three times more likely to develop bacterial pneumonia than nonsmokers. Current smoking status was significant, but a past history of smoking was not. CONCLUSIONS: Bacterial pneumonia is a major source of morbidity, even for persons on potent antiretroviral therapy, including those with high CD4 cells. Efforts to reduce this illness should stress the importance of uninterrupted antiretroviral therapy and attainment and/or maintenance of nonsmoking status.

Long-term efficacy and safety of tipranavir boosted with ritonavir in HIV-1-infected patients failing multiple protease inhibitor regimens: 80-week data from a phase 2 study.

BACKGROUND: BI 1182.2, an open-label, randomized, multicenter, phase 2 study, evaluated efficacy and tolerability of the protease inhibitor (PI) tipranavir (TPV; 500 mg twice daily or 1000 mg twice daily) administered with ritonavir (100 mg twice daily) in combination with 1 nucleoside reverse transcriptase inhibitor and 1 nonnucleoside reverse transcriptase inhibitor in multiple PI-experienced HIV-1-infected patients. METHODS: Forty-one patients were evaluated in 2 arms: low-dose (19 patients) or high-dose (22 patients) ritonavir-boosted tipranavir (TPV/r). Primary endpoints were change from baseline in HIV-1 RNA concentrations at weeks 16, 24, 48, and 80 and percentage of patients with plasma HIV-1 RNA levels lower than the limit of quantitation. Safety was evaluated by adverse events (AEs), grade 3/4 abnormalities, and serious AEs. RESULTS: Of all patients, 59% were still receiving TPV/r (14 in low-dose arm and 10 in high-dose arm) at week 80. Patients in both arms had a median >2.0-log10 reduction in plasma viral load. Intent-to-treat analysis demonstrated that a similar proportion of patients in the high-dose and low-dose groups achieved plasma HIV-1 RNA levels <50 copies/mL at week 80 (43% vs. 32%; P = 0.527). The most frequently observed AEs were diarrhea, headache, and nausea. CONCLUSION: TPV/r combined with other active antiretroviral agents can provide a durable treatment response for highly treatment-experienced patients.

Symptomatic orthostasis with extended-release nifedipine and protease inhibitors.

Human immunodeficiency virus (HIV) protease inhibitors are prone to drug interactions with other agents. As individuals with HIV infection live longer, the clinical significance of many interactions is becoming recognized. A 51-year-old man with HIV infection who was receiving extended-release nifedipine developed symptomatic orthostasis and heart block after starting antiretroviral therapy that included nelfinavir. He experienced dizziness, fatigue, and hypotension and developed complete heart block with a junctional escape rhythm. Electrocardiogram abnormalities abated within 24 hours of discontinuing antiretroviral therapy. The patient developed orthostatic symptoms after restarting nelfinavir. He was switched successfully to an efavirenz-based regimen. Subsequent administration of antiretroviral therapy containing ritonavir and indinavir with extended-release nifedipine resulted in recurrence of his orthostatic symptoms. Discontinuation of atenolol, and nifedipine dosage reduction by 50% were effective in managing his orthostatic changes. Careful monitoring by clinicians is necessary when concomitant administration of HIV protease inhibitors are prescribed with other agents that are metabolized through the cytochrome P450 system.

Microbiological, biological, and chemical weapons of warfare and terrorism.

Microbiological, biological, and chemical toxins have been employed in warfare and in terrorist attacks. In this era, it is imperative that health care providers are familiar with illnesses caused by these agents. Botulinum toxin produces a descending flaccid paralysis. Staphylococcal enterotoxin B produces a syndrome of fever, nausea, and diarrhea and may produce a pulmonary syndrome if aerosolized. Clostridium perfringens epsilon-toxin could possibly be aerosolized to produce acute pulmonary edema. Ricin intoxication can manifest as gastrointestinal hemorrhage after ingestion, severe muscle necrosis after intramuscular injection, and acute pulmonary disease after inhalation. Nerve agents inhibit acetylcholinesterase and thus produce symptoms of increased cholinergic activity. Ammonia, chlorine, vinyl chloride, phosgene, sulfur dioxide, and nitrogen dioxide, tear gas, and zinc chloride primarily injure the upper respiratory tract and the lungs. Sulfur mustard (and nitrogen mustard) are vesicant and alkylating agents. Cyanide poisoning ranges from sudden-onset headache and drowsiness to severe hypoxemia, cardiovascular collapse, and death. Health care providers should be familiar with the medical consequences of toxin exposure, and understand the pathophysiology and management of resulting illness.