Association Between Minimum Inhibitory Concentration, Beta-lactamase Genes and Mortality for Patients Treated With Piperacillin/Tazobactam or Meropenem From the MERINO Study.

INTRODUCTION: This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the MERINO trial. METHODS: Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations. RESULTS: In total, 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam nonsusceptible breakpoint (MIC >16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% confidence interval [CI] 2.8-87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3%-15%) and 8% (95% CI 2%-15%) for the original PA population and the post hoc MA populations, which reduced to 5% (95% CI -1% to 10%) after excluding strains with piperacillin/tazobactam MIC values >16 mg/L. Isolates coharboring extended spectrum ß-lactamase (ESBL) and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-day mortality of 14% (95% CI 2%-28%). CONCLUSIONS: After excluding nonsusceptible strains, the 30-day mortality difference from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA coharboring ESBLs suggests that meropenem remains the preferred choice for definitive treatment of ceftriaxone nonsusceptible Escherichia coli and Klebsiella.

Infection in a neonate caused by Pichia fabianii: importance of molecular identification.

Pichiafabianii, an uncommon yeast species recovered from clinical specimens, was documented as the cause of an infection in a 5-week-old female twin delivered at 25 and 3/7 weeks. She developed respiratory distress syndrome and necrotizing enterocolitis. At the time of the infection, she was febrile, thrombocytopenic, and still was requiring minimal ventilatory support. Blood cultures drawn on two consecutive days were positive for a germ tube negative yeast. Phenotypic methods including carbohydrate fermentations and assimilations (API 20C AUX) did not identify the yeast. Sequencing of D1/D2 domain of the large subunit rDNA was performed in one laboratory and sequencing a subunit of D2 performed in a second laboratory identified the yeast as P. fabianii. The organism was susceptible in vitro to amphotericin B, fluconazole and 5-fluorocytosinc. The patient responded to amphotericin B and removal of her vascular catheter. This case illustrates that there are an increasing number of fungi that may be pathogenic. Phenotypic tests may fail to identify them, emphasizing the need for commercially available, molecular based assays for identification.

Otitis caused by Scedosporium apiospermum in an immunocompetent child.

Scedosporium apiospermum (Pseudallescheria boydii) is a ubiquitous saprophytic mold. It is considered an infrequent but important and emerging human pathogen, mostly in immunocompromised hosts. Otomycosis secondary to S. apiospermum is extremely rare. We report an 8-year-old immunocompetent male who developed otitis media and otitis externa from S. apiospermum, which was successful treated with combination of surgical debridement and topical clotrimazole therapy. A brief literature review of infections caused by S. apiospermum follows the case presentation.

Tumor-induced hypercalcemia: predictors of early mortality.

OBJECTIVE: To delineate the demographics and predictors of early mortality associated with tumor-induced hypercalcemia (TIH) amongst cancer patients in Pakistan. SETTING: A tertiary care hospital in Pakistan. PATIENTS AND METHODS: Retrospective analysis of patients with cancers, presenting with TIH and admitted to the hospital between January 1988 and December 1997, was carried out. RESULTS: Eighty-four patients (56 males and 28 females) were diagnosed to have TIH. The mean age at the time of presentation was 55 +/- 14 years. Twenty-five percent of the patients each had multiple myeloma and hepatocellular carcinoma whereas 20% of the patients had underlying breast cancer. Other malignancies included lung cancer, gall bladder cancer and colorectal carcinomas. Univariate analysis revealed male sex (p < 0.04), underlying diagnosis other than multiple myeloma (p < 0.025) and a high TLC (p < 0.05) at presentation, as predictors of an early mortality. CONCLUSION: Multiple myeloma, hepatoma and breast carcinoma were common cancers causing TIH. One-third patients died within first few days. Male sex, a high white cell count and an underlying diagnosis other than multiple myeloma predicted early mortality.

Epidemiology of blood-borne viruses: a study of healthy blood donors in Southern Pakistan.

There are only a few published reports regarding the prevalence of hepatitis B virus, hepatitis C virus and human immunodeficiency virus in Pakistani blood donors. The true extent of the prevalence of these viral infections in healthy adults in unclear. We examined blood donors attending the Aga Khan University Hospital and blood donation camps in the cities of Karachi and Hyderabad, Pakistan for the presence of hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV) and human immunodeficiency virus (anti-HIV). Relationship of anti HCV to the surrogate marker alanine aminotransferase (ALT) was also examined. Prevalence of HBsAg was found to be 2.28% (1,173/51,257), anti HCV was 1.18%(198/16,705) and that of anti HIV to be 0.02% (10/51,257). Higher rate of prevalence of HBsAg and anti HCV was observed in the younger age group of 21 to 30 years. Male to female ratio for HBsAg was 2.5:1 and for anti HCV 1:1. Seropositivity for HBsAg was significantly greater than anti HCV (p < 0.0001). No clear relationship was found between high ALT (>55 U/l) and anti HCV positivity. Further examination of seropositive samples for HIV revealed only one donor to be positive by Western blot also. Prevalence of hepatitis B and C in the adult blood donor population in Southern Pakistan is higher than western countries but is similar to regional countries. This study also suggested that high ALT is not a useful surrogate marker for hepatitis C virus. Prevalence of HIV in this donor population is very low and is comparable to the western countries.