Impact of Empiric Antimicrobial Therapy on Outcomes in Patients with Escherichia coli and Klebsiella pneumoniae Bacteremia: A Cohort Study

<p>Abstract</p> <p>Background</p> <p>It is unclear whether appropriate empiric antimicrobial therapy improves outcomes in patients with bacteremia due to <it>Escherichia coli </it>or <it>Klebsiella</it>. The objective of this study is to assess the impact of appropriate empiric antimicrobial therapy on in-hospital mortality and post-infection length of stay in patients with <it>Escherichia coli </it>or <it>Klebsiella </it>bacteremia while adjusting for important confounding variables.</p> <p>Methods</p> <p>We performed a retrospective cohort study of adult patients with a positive blood culture for <it>E. coli </it>or <it>Klebsiella </it>between January 1, 2001 and June 8, 2005 and compared in-hospital mortality and post-infection length of stay between subjects who received appropriate and inappropriate empiric antimicrobial therapy. Empiric therapy was defined as the receipt of an antimicrobial agent between 8 hours before and 24 hours after the index blood culture was drawn and was considered appropriate if it included antimicrobials to which the specific isolate displayed <it>in vitro </it>susceptibility. Data were collected electronically and through chart review. Survival analysis was used to statistically assess the association between empiric antimicrobial therapy and outcome (mortality or length of stay). Multivariable Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI).</p> <p>Results</p> <p>Among 416 episodes of bacteremia, 305 (73.3%) patients received appropriate empiric antimicrobial therapy. Seventy-one (17%) patients died before discharge from the hospital. The receipt of appropriate antimicrobial agents was more common in hospital survivors than in those who died (p = 0.04). After controlling for confounding variables, there was no association between the receipt of appropriate empiric antimicrobial therapy and in-hospital mortality (HR, 1.03; 95% CI, 0.60 to 1.78). The median post-infection length of stay was 7 days. The receipt of appropriate antimicrobial agents was not associated with shortened post-infection length of stay, even after controlling for confounding (HR, 1.11; 95% CI 0.86 to 1.44).</p> <p>Conclusion</p> <p>Appropriate empiric antimicrobial therapy for <it>E. coli </it>and <it>Klebsiella </it>bacteremia is not associated with lower in-hospital mortality or shortened post-infection length of stay. This suggests that the choice of empiric antimicrobial agents may not improve outcomes and also provides data to support a randomized trial to test the hypothesis that use (and overuse) of broad-spectrum antibiotics prior to the availability of culture results is not warranted.</p

Causes of death by category.

<p>Categorized by duration of antiretroviral therapy (ART) at the time of death. Pre-ART deaths occurred in subjects who were HIV-positive and eligible for ART but had not yet received it (CD4 cell count <200 cells/mm³) or those who had received <7 days of ART. Early ART deaths occured between 7–90 days of ART. Late ART deaths occurred after >90 days of ART.</p>a<p>All causes of death (immediate and contributing) are included and each subject may have multiple causes of death.</p>b<p>Non-infectious organ dysfunction, ie. pulmonary embolus or end stage renal disease.</p>c<p>At least one cause of death was revealed only through the post-mortem investigations.</p

Immediate and contributing cause(s) of death with supporting clinical, microbiologic and histologic findings.

<p><b>Symbols</b>: ∧pre-mortem culture;</p>∼<p>post-mortem culture;</p>&<p>detected by PCR;</p>%<p>Ziehl-Neelson stain positive;</p>*<p>unsuspected at time of death;</p>#<p>not satisfactorily explained by post-mortem technique.</p><p><b>Abbreviations</b>: <b>AFB</b> – acid fast bacilli; <b>ag</b> – antigen; <b>ART</b> – antiretroviral therapy; <b>ATN</b> – acute tuberular necrosis; <b>BM</b> – bone marrow; <b>CN</b> – cranial nerve; <b>CSF</b> – cerebrospinal fluid; <b>CMV</b> – cytomegalovirus, <b>CVA</b> – cerebrovascular accident; <b>DIC</b> – disseminated intravascular coagulation;<b>ESRD</b> – end stage renal disease; <b>GI</b> – gastrointestingal; <b>gran.</b> – granulmonatous; <b>HA</b> – headache; <b>HSM</b> – hepatosplenomegaly; <b>HTN</b> – hypertension; <b>ICH</b> – intracerebral hemorrhage; <b>inflam. –</b> inflammation; <b>IRIS –</b> immune reconstitution inflammatory syndrome; <b>KS –</b> Kaposi sarcoma; <b>LAD –</b> lymphadenopathy; <b>LN –</b> lymph node; <b>MAC –</b> Mycobacterium avium complex; <b>MTB –</b> Mycobacterium tuberculosis; <b>nec. –</b> necrotizing; <b>NHL</b> – non-Hodgkins lymhoma; <b>PCR –</b> polymerase chain reaction; <b>PJP –</b> Pneumocystis iroveci pneumonia; <b>PNA –</b> pneumonia; <b>pulm –</b> pulmonary; <b>TBT –</b> tuberculosis therapy; <b>vol. –</b> volume.</p

Pre-mortem characteristics of the study population.

<p>Categorized by duration of antiretroviral therapy (ART) at the time of death. Pre-ART deaths occurred in subjects who were HIV-positive and eligible for ART but had not yet received it (CD4 cell count <200 cells/mm³) or those who had received <7 days of ART. Early ART deaths occurred between 7–90 days of ART. Late ART deaths occurred after >90 days of ART.</p>a<p>CD4 count measured most recently prior to death.</p

Outcomes of Patients on Dual-Boosted PI Regimens: Experience of the Swiss HIV Cohort Study

Dual-boosted protease inhibitors (DBPI) are an option for salvage therapy for HIV-1 resistant patients. Patients receiving a DBPI in the Swiss HIV Cohort Study between January1996 and March 2007 were studied. Outcomes of interest were viral suppression at 24 weeks. 295 patients (72.5%) were on DBPI for over 6 months. The median duration was 2.2 years. Of 287 patients who had HIV-RNA >400 copies/ml at the start of the regimen, 184 (64.1%) were ever suppressed while on DBPI and 156 (54.4%) were suppressed within 24 weeks. The median time to suppression was 101 days (95% confidence interval 90–125 days). The median number of past regimens was 6 (IQR, 3–8). The main reasons for discontinuing the regimen were patient's wish (48.3%), treatment failure (22.5%), and toxicity (15.8%). Acquisition of HIV through intravenous drug use and the use of lopinavir in combination with saquinavir or atazanavir were associated with an increased likelihood of suppression within 6 months. Patients on DBPI are heavily treatment experienced. Viral suppression within 6 months was achieved in more than half of the patients. There may be a place for DBPI regimens in settings where more expensive alternates are not available

Simultaneous <i>C. neoformans</i> pneumonia and paradoxical <i>M. tuberculosis</i> Immune Reconstitution Inflammatory Syndrome (IRIS).

<p>At the time of death, this patient (E33) had been on anti-tuberculosis therapy for pulmonary tuberculosis for 5 months (with good response to treatment) and antiretroviral therapy for 1 month. Histologic sections demonstrate (a) suppurative consolidation of the lungs with (b) cryptococcal organisms apparent on Grocott’s Methanamine Silver (GMS) stain. Kidney (c) and spleen (d) demonstrate well formed necrotizing granulomatous inflammation, with negative Ziehl-Neelsen and GMS stains for organisms; these were thought to represent an exuberant inflammatory response due to paradoxical TB IRIS.</p

The yield of needle autopsy by site and investigation.

a<p>Lymph nodes were biopsied in patients with palpable lymphadenopathy on post-mortem exam.</p>b<p>Skin biopsy was performed in patients with rash on post-mortem exam.</p>c<p>Heart was biopsied if pre-mortem history was suggestive of cardiac cause of death.</p