In the three years between November 1989 and October 1992, an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) affected 990 patients at a university hospital. The distribution of patients with carriage, colonization or infection was investigated prospectively. Nosocomial acquisition was confirmed in at least 928 patients, 525 of whom were identified from clinical specimens as being infected (n = 418) or colonized (n = 107) by MRSA. An additional 403 patients were identified from screening specimens, of whom 58 subsequently became infected and 18 colonized. Screening of the nose, throat and perineum detected 98% of all carriers. Of the 580 infections in 476 patients, surgical wound, urinary tract and skin infections accounted for 58% of the infections. Of the 476 infected patients, death was attributable to MRSA infection in 13%. Colonization with MRSA was found in 127 patients and 42% of 165 colonized sites were the skin. Auto-infection from nasal carriage or cross-infection, probably via staff hands, seemed to be the most common mode of acquisition of MRSA infections.

Better adherence to IDSA guidelines would help to improve survival among patients with severe CAP. Pseudomonas coverage should be considered for patients with chronic obstructive pulmonary disease, malignancy, or recent antibiotic exposure.

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Objective. Findings from animal studies have suggested that leflunomide may be a human teratogen. In the only human cohort study published to date, an increase in adverse outcomes in pregnancies after exposure to leflunomide was not detected. The aim of the present analysis was to expand on the previously published data with a description of birth outcomes among women who did not meet the previous cohort study criteria but who were exposed to leflunomide either during pregnancy or prior to conception.Methods. Data on pregnancy exposures and outcomes were collected from 45 pregnant women who had contacted counseling services of the Organization of Teratology Information Specialists in the US or Canada between 1999 and 2009. Sixteen women were exposed to leflunomide during the first trimester of pregnancy and 29 women were exposed preconception.Results. All 16 of the pregnancies with leflunomide exposure during pregnancy and 27 (93%) of the pregnancies with exposure prior to conception resulted in liveborn infants. There were 2 infants with major malformations from mothers who were exposed during pregnancy, and no malformations reported in the preconception group. There was a potential known alternative etiology for at least some of the defects observed.Conclusion. These data provide additional reassurance to women who inadvertently become pregnant while taking leflunomide and who undergo the washout procedure, as well as women who discontinue the medication prior to conception but have no prepregnancy documentation of drug clearance. However, until more conclusive data become available, women receiving leflunomide should be advised to use contraceptive methods and avoid pregnancy.

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Patients with severe hospital-acquired pneumonia admitted to the ICU present high mortality. The presence of septic shock and chronic obstructive pulmonary disease in conjunction with specific microorganisms are associated with a poor prognosis. Local epidemiological data combined with a patient-based approach may allow a more accurate therapy decision making.

The use of drug combinations in clinical trials is increasingly common during the last years since a more favorable therapeutic response may be obtained by combining drugs. In phase I clinical trials, most of the existing methodology recommends a one unique dose combination as “optimal,” which may result in a subsequent failed phase II clinical trial since other dose combinations may present higher treatment efficacy for the same level of toxicity. We are particularly interested in the setting where it is necessary to wait a few cycles of therapy to observe an efficacy outcome and the phase I and II population of patients are different with respect to treatment efficacy. Under these circumstances, it is common practice to implement two‐stage designs where a set of maximum tolerated dose combinations is selected in a first stage, and then studied in a second stage for treatment efficacy. In this article we present a new two‐stage design for early phase clinical trials with drug combinations. In the first stage, binary toxicity data is used to guide the dose escalation and set the maximum tolerated dose combinations. In the second stage, we take the set of maximum tolerated dose combinations recommended from the first stage, which remains fixed along the entire second stage, and through adaptive randomization, we allocate subsequent cohorts of patients in dose combinations that are likely to have high posterior median time to progression. The methodology is assessed with extensive simulations and exemplified with a real trial.