Acute Liver Failure and Fever of Unknown Origin.

We describe a case of acute liver failure in a woman in whom a diagnosis was initially unable to be established. The patient rapidly deteriorated, requiring admission to the intensive care unit, and was placed under consideration for liver transplantation. On consultation with the infectious disease service, thorough history taking was performed that uncovered salient epidemiologic information pointing toward the eventual diagnosis of disseminated histoplasmosis. We discuss aspects of diagnosis and management, including the management of immune reconstitution syndrome which complicated treatment.

Treatment with fluoroquinolones or with beta-lactam-beta-lactamase inhibitor combinations is a risk factor for isolation of extended-spectrum-beta-lactamase-producing Klebsiella species in hospitalized patients.

Antibiotic exposure exerts strong selective pressure and is an important modifiable risk factor for antibiotic resistance. We aimed to identify the role of various antibiotics as risk factors for the isolation of extended-spectrum-beta-lactamase (ESBL)-producing Klebsiella spp. in hospitalized patients at a tertiary-care hospital. A parallel multivariable model was created to compare two groups of cases with either nosocomially acquired ESBL- or non-ESBL-producing Klebsiella spp. to a common control group of hospitalized patients (a case-case-control design). Seventy-eight ESBL cases, 358 non-ESBL cases, and 444 controls were analyzed. Significant factors associated with the isolation of Klebsiella spp. were an age of >65 years, transfer from a health care facility, an intensive care unit (ICU) stay, and the presence of a comorbid malignancy or lung, hepatic, or renal disease. A propensity score was generated from the above, and our ability to discriminate between Klebsiella cases and controls (area under the receiver-operating-characteristic [ROC] curve, 0.78) was good. The ESBL phenotype was tightly linked with fluoroquinolone resistance (95% versus 18%, P < 0.001). Factors associated with isolation of ESBL Klebsiella spp. in a multivariable analysis, adjusting for the propensity score, included exposure to beta-lactam-beta-lactamase inhibitor combinations (odds ratio [OR], 10.17; 95% confidence interval [CI], 1.19 to 86.92) and to fluoroquinolones (OR, 2.86; 95% CI, 1.37 to 5.97). Exposure to broad-spectrum cephalosporins was statistically associated with ESBL Klebsiella spp. only among the subgroup of patients not treated with fluoroquinolones. In our institution, where the ESBL-producing-Klebsiella phenotype is coselected with fluoroquinolone resistance, fluoroquinolone and beta-lactam-beta-lactamase inhibitor combinations, rather than cephalosporins, are the main risk factors for ESBL isolates. Formulary interventions to limit the spread of ESBL-producing isolates should be tailored to each setting.

Methicillin-resistant Staphylococcus aureus colonization, behavioral risk factors, and skin and soft-tissue infection at an ambulatory clinic serving a large population of HIV-infected men who have sex with men.

We conducted a prospective cohort study of 795 outpatients, many of whom were human immunodeficiency virus-infected men who have sex with men, to characterize risk of skin and soft-tissue infection (SSTI) associated with methicillin-resistant Staphylococcus aureus (MRSA) nares and perianal colonization. Multivariate analysis revealed that perianal colonization, drug use, and prior SSTIs were strongly associated with development of an SSTI. Of the patients who were colonized with MRSA at study entry, 36.7% developed an SSTI during the ensuing 12 months, compared with 8.1% of persons who were not colonized with MRSA.

Interleukin 12 and interferon-gamma synthetic deficiency is associated with dendritic cell cytopenia after cardiac surgery.

Traumatic or inflammatory injury associates with deactivation of monocytes and impaired synthesis of proinflammatory cytokines. We conducted a prospective, observational study to test whether cardiac surgery additionally impaired dendritic and natural killer (NK) cell functions responsible for innate immune production of interleukin (IL)-12-dependent interferon (IFN)-gamma in response to bacteria or toll-like receptor agonists. Blood samples were taken just before induction of anesthesia and 24 h postoperatively. LPS- and fixed Staphylococcus aureus-inducible IFNgamma synthesis in whole blood culture after surgery was reduced to 5% of preoperative values (P < 0.001). Production of IL-12 p70, a critical inducer of IFNgamma in the innate immune response, was reduced to 30% of that produced by preoperative samples (P = 0.013). Circulating CD11c, DR myeloid dendritic cells (DC) that are known sources of IL-12 p70 in normal blood, declined to approximately 25% of presurgical numbers (P = 0.004). Experimental depletion of CD11c, but not CD14, cells from normal peripheral blood mononuclear cell (PBMC) similarly disabled Staphylococcus aureus Cowan 1 (SAC)-induced production of IL-12 p70 and IFNgamma. Consistent with SAC-induced IFNgamma expression in CD56 NK and NK-T cells, CD56 depletion ablated IFNgamma production in normal whole blood. However, repletion of IL-12 p70, IL-18, IL-15, and IL-23 in postoperative blood failed to restore presurgical levels of IFNgamma synthesis (P < 0.05). We conclude that DC cytopenia after major surgery is sufficient to explain postoperative IL-12 p70 and IFNgamma synthetic deficiency. In addition, postoperative blood became hyporesponsive to IFNgamma-inducing cytokines as a further contribution to IFNgamma insufficiency. The novel finding of DC cytopenia after major surgery may portend a lack of other immunologic functions provided by this potent accessory cell population.