Marco R. Scipione

Monotherapy with Fluoroquinolone or Trimethoprim-Sulfamethoxazole for Treatment of Stenotrophomonas maltophilia Infections

ABSTRACT The treatment of choice for Stenotrophomonas maltophilia is trimethoprim-sulfamethoxazole (SXT). Fluoroquinolones (FQs) have in vitro activity against S. maltophilia; however, there is limited published information on their effectiveness. The purpose of this study is to compare the effectiveness of FQs and SXT for the treatment of S. maltophilia. A retrospective review of 98 patients with S. maltophilia infections who received SXT or FQ monotherapy was conducted. Patients ≥18 years old with a positive culture for S. maltophilia and clinical signs of infection who received treatment for ≥48 h were included. Microbiological cure and clinical response were evaluated at the end of therapy (EOT). In-hospital mortality and isolation of nonsusceptible isolates were also evaluated. Thirty-five patients received SXT, and 63 patients received FQ; 48 patients received levofloxacin, and 15 patients received ciprofloxacin. The most common infection was pulmonary. The overall microbiological cure rate at EOT was 63%. Thirteen of 20 patients (65%) who received SXT and 23 of 37 patients (62%) who received FQ had microbiological cure at EOT (P = 0.832). The overall clinical success rate was 55%, 52% for those who received FQ and 61% for those who received SXT (P = 0.451). In-hospital mortality was 24%, with similar rates in the two groups (25% for FQ versus 22% for SXT; P = 0.546). Development of resistance on repeat culture was 30% for FQ and 20% for SXT (P = 0.426). Fluoroquinolone and SXT monotherapies may be equally effective for the treatment of S. maltophilia infections. Resistance was documented in subsequent isolates of S. maltophilia in both groups.

Risk Factors for Treatment Failure of Polymyxin B Monotherapy for Carbapenem-Resistant Klebsiella pneumoniae Infections

ABSTRACT Polymyxins are reserved for salvage therapy of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Though synergy has been demonstrated for the combination of polymyxins with carbapenems or tigecycline, in vitro synergy tests are nonstandardized, and the clinical effect of synergy remains unclear. This study describes outcomes for patients with CRKP infections who were treated with polymyxin B monotherapy. We retrospectively reviewed the medical records of patients with CRKP infections who received polymyxin B monotherapy from 2007 to 2011. Clinical, microbiology, and antimicrobial treatment data were collected. Risk factors for treatment failure were identified by logistic regression. Forty patients were included in the analysis. Twenty-nine of 40 (73%) patients achieved clinical cure as defined by clinician-documented improvement in signs and symptoms of infections, and 17/32 (53%) patients with follow-up culture data achieved microbiological cure. End-of-treatment mortality was 10%, and 30-day mortality was 28%. In a multivariate analysis, baseline renal insufficiency was associated with a 6.0-fold increase in clinical failure after adjusting for septic shock (odds ratio [OR] = 6.0; 95% confidence interval [CI] = 1.22 to 29.59). Breakthrough infections with organisms intrinsically resistant to polymyxins occurred in 3 patients during the treatment. Eighteen of 40 (45%) patients developed a new CRKP infection a median of 23 days after initial polymyxin B treatment, and 3 of these 18 infections were polymyxin resistant. The clinical cure rate achieved in this retrospective study was 73% of patients with CRKP infections treated with polymyxin B monotherapy. Baseline renal insufficiency was a risk factor for treatment failure after adjusting for septic shock. Breakthrough infections with organisms intrinsically resistant to polymyxin B and development of resistance to polymyxin B in subsequent CRKP isolates are of concern.

Extended-Infusion versus Standard-Infusion Piperacillin-Tazobactam for Sepsis Syndromes at a Tertiary Medical Center

ABSTRACT Piperacillin-tazobactam (PTZ) is frequently used as empirical and targeted therapy for Gram-negative sepsis. Time-dependent killing properties of PTZ support the use of extended-infusion (EI) dosing; however, studies have shown inconsistent benefits of EI PTZ treatment on clinical outcomes. We performed a retrospective cohort study of adult patients who received EI PTZ treatment and historical controls who received standard-infusion (SI) PTZ treatment for presumed sepsis syndromes. Data on mortality rates, clinical outcomes, length of stay (LOS), and disease severity were obtained. A total of 843 patients (662 with EI treatment and 181 with SI treatment) were available for analysis. Baseline characteristics of the two groups were similar, except for fewer female patients receiving EI treatment. No significant differences between the EI and SI groups in inpatient mortality rates (10.9% versus 13.8%; P = 0.282), overall LOS (10 versus 12 days; P = 0.171), intensive care unit (ICU) LOS (7 versus 6 days; P = 0.061), or clinical failure rates (18.4% versus 19.9%; P = 0.756) were observed. However, the duration of PTZ therapy was shorter in the EI group (5 versus 6 days; P < 0.001). Among ICU patients, no significant differences in outcomes between the EI and SI groups were observed. Patients with urinary or intra-abdominal infections had lower mortality and clinical failure rates when receiving EI PTZ treatment. We did not observe significant differences in inpatient mortality rates, overall LOS, ICU LOS, or clinical failure rates between patients receiving EI PTZ treatment and patients receiving SI PTZ treatment. Patients receiving EI PTZ treatment had a shorter duration of PTZ therapy than did patients receiving SI treatment, and EI dosing may provide cost savings to hospitals.

Multidrug-Resistant Bacteroides fragilis Bacteremia in a US Resident: An Emerging Challenge

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.

Comparison of Rates of Nephrotoxicity Associated with Vancomycin in Combination with Piperacillin‐Tazobactam Administered as an Extended versus Standard Infusion

Despite recent reports of relatively high rates (16–37%) of acute kidney injury (AKI) in patients receiving the combination of intravenous piperacillin‐tazobactam (PTZ) and vancomycin, data are limited evaluating the impact of PTZ infusion strategy on the occurrence of nephrotoxicity. The objective of this study was to compare the rates of nephrotoxicity in patients receiving vancomycin in combination with PTZ administered as an extended infusion (EI) versus a standard infusion (SI).

Allergic Reactions in Hospitalized Patients With a Self-Reported Penicillin Allergy Who Receive a Cephalosporin or Meropenem

Background: Cefepime and meropenem are used frequently in hospitalized patients for broad-spectrum empiric coverage, however, practitioners are often reluctant to prescribe these antibiotics for patients with a self-reported nonsevere, nontype I allergic reaction to penicillin. Methods: Retrospective review of electronic medical records of adults with a self-reported allergy to penicillin who received at least 1 dose of cefepime, ceftriaxone, cefoxitin, cephalexin, or meropenem to assess incidence and type of allergic reactions. Results: Of 175 patients included, 10 (6%) patients experienced an allergic reaction. The incidence for individual study drugs were cefepime 6% (6 of 96), meropenem 5% (3 of 56), cefoxitin 8% (1 of 13), ceftriaxone 0% (0 of 69), and cephalexin 0% (0 of 8). The majority of patients experienced a rash with or without pruritus and fever. Patients with a concomitant “sulfa” allergy (odds ratio [OR] 5.4, 95% confidence interval [CI] 1.4-21, P = .02) or ≥3 other drug allergies (OR 6.4, 95% CI 1.3-32, P = .025) were more likely to have an allergic reaction. Conclusions: In one of the largest retrospective reviews of hospitalized patients who received full dose therapy with cefepime, ceftriaxone, and meropenem, the incidence of allergic reactions was low and reactions were mild. Cefepime, ceftriaxone, and meropenem can be considered for use in patients with a self-reported nontype I penicillin allergy.

Safety and Effectiveness of Intravenous Pentamidine for Prophylaxis of Pneumocystis jirovecii Pneumonia in Pediatric Hematology/Oncology Patients.

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.

Initial Therapy for Mild to Moderate Clostridium difficile Infection: Exploring the Role of Oral Metronidazole Versus Vancomycin in 168 Hospitalized Patients

BackgroundOral vancomycin is being increasingly used for treatment of Clostridium difficile infection (CDI), although the feasibility for such approach and avoidance of currently recommended oral metronidazole for mild to moderate (mm)-CDI remain uncertain. We sought to assess treatment response in hospitalized patients with mm-CDI at our university medical center. MethodsStandard Infectious Diseases Society of America and Society for Healthcare Epidemiology of America definitions were used. Primary outcomes included rate of treatment response and infection recurrence following therapy. ResultsAmong 513 total cases of CDI between 2011 and 2013, 168 were mm-CDI and were further analyzed. Overall treatment responses to oral vancomycin were 97% versus 82% in patients given metronidazole (P = 0.002). Overall rate of CDI recurrence was 13% following vancomycin versus 9% following metronidazole treatment (P = 0.4). In 85 patients with NAP1 (North American PFGE type 1) CDI, vancomycin and metronidazole yielded similar response (97% vs 98%, P = 0.13), whereas in 83 patients with non-NAP1 CDI, rate of treatment response to vancomycin was higher (98% vs 78% with metronidazole, P = 0.007). In a regression analysis, initial therapy with metronidazole was an independent predictor of treatment failure (odds ratio, 8.4; 95% confidence interval, 1.75–40; P = 0.007) after controlling for hypoalbuminemia (<3 g/dL), concurrent use of proton pump inhibitors, chronic liver disease, community-onset CDI, age older than 65 years, and presence of more than 3 comorbidities. In the subset of 91 patients treated with metronidazole, presence of chronic liver disease (odds ratio, 4.4; 95% confidence interval, 1.19–16.4; P = 0.027) was associated with treatment failure. ConclusionsOral metronidazole therapy for mm-CDI in hospitalized patients might not be optimal and needs further reassessment.

Evaluation of Treatment Courses When Vancomycin Is Given Every 8 Hours in Adult Patients

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.

Readministration of drotrecogin alfa (activated) in an adult with severe sepsis

PURPOSE The case of a patient with severe, multidrug-resistant, postoperative sepsis who was successfully treated with drotrecogin alfa (activated) on two occasions is reported. SUMMARY After a thigh debridement procedure, a 55-year-old African-American woman developed systemic inflammatory response syndrome (SIRS) secondary to necrotizing fasciitis. Despite empiric treatment including piperacillin-tazobactam and vancomycin, the patient remained severely hemodynamically unstable, exhibiting signs of multiorgan failure and requiring mechanical ventilation and the placement of a tracheostomy tube. After the administration of i.v. drotrecogin alfa (activated) 160 mg (24 μg/kg/hr) over 96 hours in combination with standard i.v. antimicrobials and vasopressin, the patients hemodynamic status improved considerably. About three weeks later, the patient again developed SIRS that was refractory to standard therapies. After the results of laboratory cultures indicated ventilator-associated pneumonia due to multidrug-resistant Klebsiella pneumoniae, the woman received a second course of drotrecogin alfa and other therapies. Her condition improved and she was extubated and eventually transferred to a medical-surgical unit for continued care. While drotrecogin alfa, a recombinant form of human activated protein C (APC), has been shown to reduce mortality in adults with severe sepsis and acute organ dysfunction, previous reports indicated an increased risk of thrombotic events with the use of the drug, and there is speculation that the development of anti-APC antibodies might result in a diminished therapeutic response. In the case described here, there were no thrombotic events during or after either drotrecogin alfa infusion and no clinical evidence of antibody formation. CONCLUSION A patient received two complete courses of drotrecogin alfa (activated) without any treatment-related complications.