Logistic-regression analysis for factors associated with 28-day mortality.

<p>Logistic-regression analysis for factors associated with 28-day mortality.</p

Review of studies post-1990s comparing the associated mortality of single-positive (SP) versus multiple-positive (MP) blood cultures based on the identity of the microorganism.

<p>Review of studies post-1990s comparing the associated mortality of single-positive (SP) versus multiple-positive (MP) blood cultures based on the identity of the microorganism.</p

Should we treat patients with only one set of positive blood cultures for extensively drug-resistant <i>Acinetobacter baumannii</i> the same as multiple sets?

<div><p><i>Acinetobacter</i> species are not considered skin commensals and under-treatment is an overriding concern when caring for critically-ill patients who are mostly at risk of extensively drug-resistant <i>Acinetobacter baumannii</i> (XDRAB) infections. Hence even a single blood culture yielding XDRAB will tend to prompt intervention. However, field observations suggest that patients with single-positive blood cultures had milder disease and were more likely to be recruited in interventional studies than those with multiple-positive blood cultures, yet no distinction is made in current clinical or trial recruitment practices. To our knowledge, this is the first study to compare the clinical characteristics and outcomes of patients with single-positive versus multiple-positive blood cultures for XDRAB. In this multicenter prospective cohort study of XDRAB bacteremic patients from July 2010 to June 2015, only patients with at least two simultaneously drawn blood cultures were included. The patients were classified as having single-positive or multiple-positive blood cultures according to the number of positive blood cultures yielding XDRAB. The primary end-point was the 28-day mortality. Of a total of 155 patients enrolled, 69 had a single-positive and 86 had multiple-positive blood cultures. Leukopenia (37.2% vs. 16.2%; <i>P</i> = 0.004), thrombocytopenia (56.0% vs. 26.5%; <i>P</i> < 0.001), higher Pitt bacteremia scores (6.6 vs. 5.5, <i>P</i> = 0.03) and higher 28-day mortality rates (70.9% vs. 43.5%; <i>P</i> = 0.001) distinguished patients with multiple-positive from those with single-positive cultures. Multivariate logistic regression showed that multi-positivity independently predicted 28-day mortality (adjusted odds ratio, 2.34; 95% confidence interval (CI), 1.03–5.28; <i>P</i> = 0.04) and the Cox regression confirmed that multi-positivity (adjusted hazard ratio, 1.80; 95% CI, 1.13–2.85; <i>P</i> = 0.01) predicted rapid mortality. Patients with multiple versus single positive blood cultures yielding XDRAB had greater morbidity and mortality. Investigators and clinicians should be aware that the blood culture positivity rate impacts outcomes of XDRAB bacteremia.</p></div

Demographics and clinical characteristics of patients with either single- or multiple-positive blood cultures positive for <i>A</i>. <i>baumannii</i>.

<p>Demographics and clinical characteristics of patients with either single- or multiple-positive blood cultures positive for <i>A</i>. <i>baumannii</i>.</p

Flow diagram illustrating the selection of patients for the study.

<p>Flow diagram illustrating the selection of patients for the study.</p

Kaplan-Meier stratified by 1 set and ≥2 sets blood cultures positive for <i>A</i>. <i>baumannii</i> showing inferior survival of ≥2 sets blood cultures positive for <i>A</i>. <i>baumannii</i> compared to 1 set of <i>A</i>. <i>baumannii</i> among all <i>A</i>. <i>baumannii</i> bacteremic patients (A) and among mono-microbial <i>A</i>. <i>baumannii</i> bacteremic patients (B).

<p>Kaplan-Meier stratified by 1 set and ≥2 sets blood cultures positive for <i>A</i>. <i>baumannii</i> showing inferior survival of ≥2 sets blood cultures positive for <i>A</i>. <i>baumannii</i> compared to 1 set of <i>A</i>. <i>baumannii</i> among all <i>A</i>. <i>baumannii</i> bacteremic patients (A) and among mono-microbial <i>A</i>. <i>baumannii</i> bacteremic patients (B).</p

Multicenter Study of Trimethoprim/Sulfamethoxazole-Related Hepatotoxicity: Incidence and Associated Factors among HIV-Infected Patients Treated for <i>Pneumocystis jirovecii</i> Pneumonia

<div><p>The incidence of hepatotoxicity related to trimethoprim/sulfamethoxazole (TMP/SMX) administered at a therapeutic dose may vary among study populations of different ethnicities and hepatotoxic metabolites of TMP/SMX may be decreased by drug-drug interaction with fluconazole. We aimed to investigate the incidence of hepatotoxicity and the role of concomitant use of fluconazole in HIV-infected patients receiving TMP/SMX for <i>Pneumocystis jirovecii</i> pneumonia. We reviewed medical records to collect clinical characteristics and laboratory data of HIV-infected patients who received TMP/SMX for treatment of <i>P. jirovecii</i> pneumonia at 6 hospitals around Taiwan between September 2009 and February 2013. Hepatotoxicity was defined as 2-fold or greater increase of aminotransferase or total bilirubin level from baselines. Roussel UCLAF Causality Assessment Method (RUCAM) was used to analyze the causality of drug-induced liver injuries. <i>NAT1</i> and <i>NAT2</i> acetylator types were determined with the use of polymerase-chain-reaction (PCR) restriction fragment length polymorphism to differentiate common single-nucleotide polymorphisms (SNPs) predictive of the acetylator phenotypes in a subgroup of patients. During the study period, 286 courses of TMP/SMX treatment administered to 284 patients were analyzed. One hundred and fifty-two patients (53.1%) developed hepatotoxicity, and TMP/SMX was considered causative in 47 (16.4%) who had a RUCAM score of 6 or greater. In multivariate analysis, concomitant use of fluconazole for candidiasis was the only factor associated with reduced risk for hepatotoxicity (adjusted odds ratio, 0.372; 95% confidence interval, 0.145–0.957), while serostatus of hepatitis B or C virus, <i>NAT1</i> and <i>NAT2</i> acetylator types, or receipt of combination antiretroviral therapy was not. The incidence of hepatotoxicity decreased with an increasing daily dose of fluconazole up to 4.0 mg/kg. We conclude that the incidence of TMP/SMX-related hepatotoxicity was 16.4% in HIV-infected Taiwanese patients who received TMP/SMX for pneumocystosis. Concomitant use of fluconazole was associated with decreased risk for TMP/SMX-related hepatotoxicity.</p></div

Clinical characteristics of HIV-infected patients with and those without hepatotoxicity after receiving trimethoprim/sulfamethoxazole for treatment of <i>Pneumocystis jirovecii</i> pneumonia.

<p><b>Note:</b> Data represent the median value (range) for continuous variables and the number of cases (%) for categorical variables. N indicates the number of patients being tested.</p><p><b>Abbreviations:</b> AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; BMI, body-mass index; HBsAg, hepatitis B virus surface antigen; HCV, hepatitis C virus; IDU, injecting drug user; LDH, lactate dehydrogenase; TMP/SMX, trimethoprim/sulfamethoxazole; <i>NAT1</i>, <i>N</i>-acetyltransferase-1; <i>NAT2</i>, <i>N</i>-acetyltransferase-2.</p><p>Clinical characteristics of HIV-infected patients with and those without hepatotoxicity after receiving trimethoprim/sulfamethoxazole for treatment of <i>Pneumocystis jirovecii</i> pneumonia.</p

Study flow of HIV-infected patients who developed hepatotoxicity after treatment with trimethoprim/sulfamethoxazole.

<p>Study flow of HIV-infected patients who developed hepatotoxicity after treatment with trimethoprim/sulfamethoxazole.</p

Multivariate logistic regression for the factors associated with trimethoprim/sulfamethoxazole-related hepatotoxicity.

<p><b>Note:</b> Data represents the point estimate of the odds ratio for developing hepatotoxicity with 95% confidence interval.</p><p><b>Abbreviations:</b> BMI, body-mass index (kg/m²); TMP/SMX, trimethoprim/sulfamethoxazole.</p><p>Multivariate logistic regression for the factors associated with trimethoprim/sulfamethoxazole-related hepatotoxicity.</p