Faculty Bibliography

Treatment of Legionnaires' disease in severely ill or immunosuppressed patients presents a clinical challenge. Tigecycline (TG) achieves high concentrations intracellularly and has been shown to be effective against L. pneumophila in animal and cell models. We report our experience using TG as second-line therapy. Clinical response was seen in most patients after switching to TG alone or as a combination therapy.

We describe a case of a 72-year-old man with early-stage chronic lymphocytic leukemia (CLL) who presented with invasive nontyphoidal Salmonella (iNTS) infection, necrotizing pneumonia, and chronic infection of a hilar lymph node. Infection is a major cause of death in patients with CLL. Though few cases of iNTS infection associated with CLL have been described in the literature, to our knowledge this is the first reported case of iNTS-associated necrotizing pneumonia. Immunocompromised state in patients, even with early-stage CLL, likely predisposes them to invasive infection with intracellular organisms, such as Salmonella spp. In this case, successful treatment was achieved with prolonged course of intravenous followed by oral antibiotics without any surgical removal of infected focus.

Polymyxin B is increasingly used as a treatment of last resort for multidrug-resistant Gram-negative infections. Despite being available as a mixture of several structurally related analogues, the properties are commonly reported as an aggregate of the individual components. We compared the pharmacokinetics of individual polymyxin B components in an animal model and in humans. There were no considerable differences observed in the pharmacokinetics among major components of polymyxin B. Combining different components for pharmacokinetic analysis appeared reasonable.

Background. Mortality due to severe LD remains high with 20-25% of patients requiring mechanical ventilation. TG, a minocycline derivative, is active against L. pneumophila in animal and cell models, achieves high concentrations intracellularly and demonstrated minimal in vitro synergy with levofloxacin (LVX). Clinical data on TG for LD are limited to two case reports in immunocompromised hosts. We describe our experience with TG as salvage therapy in severely ill patients with LD. Methods. Patient demographics, clinical data and treatment details were collected retrospectively. Clinical failure was defined based on vital signs (temperature >=37.2degreeC, heart rate >=100 beats/min, respiratory rate >=24 breath/min, systolic <=100 mm Hg, oxygen saturation on room air <90%) and/or physician-documented deterioration in clinical parameters or death. Results. At our University Medical Center 12 patients with severe LD (positive Legionella urinary antigen n = 8, elevated L. pneumophilia antibody n = 4) received TG salvage therapy after failure of initial treatment with azithromycin (AZ) n = 6 or LVX and AZ n = 6 between January 2008 and February 2016. Median age of these patients was 81 (37-90) years. More than half had >=2 comorbidities, with cardiovascular and pulmonary being more common. Two patients were immunocompromised due to active chemotherapy. PSI score on admission was 130 (97-223); at the time of switch to TG, SOFA score was 6 (1-9) with respiratory worsening present in 11/12 patients after median of 4 (2-8) days of initial therapy. Seventy percent of patients required intensive care unit stay for 12 (1-18) days, 42% (5/12) had septic shock and were intubated for 10 (1-22) days. These patients received salvage therapy with TG 100 mg x 1 dose, followed by 50 mg IV q12h in addition to LVX n = 5, AZ n = 3, LVX and AZ n = 3, or as monotherapy n = 1 for median of 8 (4-17) days. After TG salvage therapy, clinical improvement was seen in 67% (8/12). Two patients died and 2 were made comfort care. No patients experienced adverse events attributable to TG salvage therapy. Total duration of therapy was 18 (9-24) days. Conclusion. This small cohort of patients provides evidence that TG can be considered for salvage therapy in patients failing macrolide or fluoroquinolone therapy

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection that can lead to significant morbidity and mortality in immunocompromised pediatric hematology/oncology patients. Trimethoprim/sulfamethoxazole is the gold standard for prophylaxis. Intravenous (IV) pentamidine is the preferred second-line agent for PCP prophylaxis at our institution and is used first-line under certain circumstances. The purpose of this study is to evaluate the effectiveness and safety of IV pentamidine for PCP prophylaxis in pediatric hematology/oncology patients. MATERIALS AND METHODS: A retrospective analysis of pediatric hematology/oncology patients (N=121) who received >/=1 dose of IV pentamidine between January 2009 and July 2014 was conducted. Electronic health records were reviewed to determine baseline characteristics, rate of breakthrough PCP infection, characteristics of IV pentamidine use, and adverse events. The follow-up period was 6 months after the last reported IV pentamidine dose or the last recorded clinic visit/hospital admission. RESULTS: No patients developed PCP during the entirety of their IV pentamidine course or during the follow-up period. Nineteen patients (16%) experienced adverse events and 5 of the 19 patients required discontinuation of IV pentamidine. CONCLUSIONS: IV pentamidine is a safe, tolerable, and effective agent for PCP prophylaxis in pediatric hematology/oncology patients and may be considered a reasonable therapeutic alternative when trimethoprim/sulfamethoxazole cannot be used for PCP prophylaxis.

We describe a case of Bacteroides fragilis bacteremia associated with paraspinal and psoas abscesses in the United States. Resistance to b-lactam/b-lactamase inhibitors, carbapenems, and metronidazole was encountered despite having a recent travel history to India as the only possible risk factor for multidrug resistance. Microbiological cure was achieved with linezolid, moxifloxacin, and cefoxitin.

BACKGROUND: Several nomograms include recommendations to give intravenous (IV) vancomycin at 8-hour dosing intervals (Q8H). However, there is a lack of detailed data regarding this dosing recommendation. METHODS: A retrospective chart review of 100 patients who received 107 treatment courses of vancomycin Q8H for at least 5 days was performed. Distribution of vancomycin trough levels and rate of nephrotoxicity were evaluated. RESULTS: Median patient age was 38 years (interquartile range [IQR] 27-50 years), median weight was 67 kg (IQR 55-79 kg), and median creatinine clearance was 124 mL/min (IQR 101-147 mL/min). Median duration of Q8H dosing was 9 days (IQR 7-12 days). Within the initial 96 hours, only 7% (7 of 104) of maximum trough concentrations were >20 mg/L (median dose 15 mg/kg [IQR 15-18 mg/kg]). After 96 hours of Q8H dosing, 34% (30 of 89) of maximum troughs were >20 mg/L (median dose 17 mg/kg [IQR 15-20 mg/kg]), P = .0005. The rate of nephrotoxicity was 4%. CONCLUSION: We observed an increase in the percentage of trough levels >20 mg/L later during treatment courses of vancomycin IV Q8H with a relatively small corresponding increase in vancomycin dose. Close monitoring of trough levels (eg, every 3 days) with prolonged courses of vancomycin IV Q8H is warranted.