Verna Welch

Incidence of Nephrotoxicity and Association With Vancomycin Use in Intensive Care Unit Patients With Pneumonia: Retrospective Analysis of the IMPACT-HAP Database

BACKGROUND The 2005 guidelines from the American Thoracic Society and the Infectious Diseases Society of America recommend vancomycin trough levels of 15 to 20 mg/L for the therapy of hospital-acquired (HAP), ventilator-associated (VAP), and health care-associated (HCAP) pneumonia. OBJECTIVE The goal of this article was to report the incidence of nephrotoxicity and associated risk factors in intensive care unit patients who received vancomycin for the treatment of HAP, VAP, and HCAP. METHODS This was a retrospective analysis of data from a multicenter, observational study of pneumonia patients. Antibiotic-associated nephrotoxicity was defined as either an increase in serum creatinine ≥0.5 mg/dL or 50% above baseline, from initiation of vancomycin to 72 hours after completion of therapy. Univariate and multivariate logistic regression analyses were performed to identify risk factors for development of renal dysfunction. RESULTS Of the 449 patients in the database, 240 received at least one dose of vancomycin and 188 had sufficient data for analysis. In these 188 patients, 63% were male. Mean (SD) age was 58.5 (17.2) years, and the mean Acute Physiology and Chronic Health Evaluation II score was 19.4 (6.4). Nephrotoxicity occurred in 29 of 188 (15.4%) vancomycin-treated patients. In multivariate analysis, initial vancomycin trough levels ≥15 mg/L (odds ratio [OR], 5.2 [95% CI, 1.9-13.9]; P = 0.001), concomitant aminoglycoside use (OR, 2.67 [95% CI, 1.09-6.54]; P = 0.03), and duration of vancomycin therapy (OR for each additional treatment day, 1.12 [95% CI, 1.02-1.23]; P = 0.02) were independently associated with nephrotoxicity. The incidence of nephrotoxicity increased as a function of the initial vancomycin trough level, rising from 7% at a trough <10 mg/L to 34% at >20 mg/L (P = 0.001). The mean time to nephrotoxicity decreased from 8.8 days at vancomycin trough levels <15 mg/L to 7.4 days at >20 mg/L (Kaplan-Meier analysis, P = 0.0003). CONCLUSIONS Nephrotoxicity may be common among intensive care unit patients with pneumonia treated with broad-spectrum antibiotic therapy that includes vancomycin. The finding that an initial vancomycin trough level ≥15 mg/L may be an independent risk factor for nephrotoxicity highlights the need for additional studies to assess current recommendations for vancomycin dosing for ICU patients with pneumonia.

Higher clinical success in patients with ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus treated with linezolid compared with vancomycin: Results from the IMPACT-HAP study

IntroductionControversy exists regarding optimal treatment for ventilator-associated pneumonia (VAP) due to methicillin-resistant Staphylococcus aureus (MRSA). The primary objective of this study was to compare clinical success of linezolid versus vancomycin for the treatment of patients with MRSA VAP.MethodsThis was a multicenter, retrospective, observational study of patients with VAP (defined according to Centers for Disease Control and Prevention criteria) due to MRSA who were treated with linezolid or vancomycin. MRSA VAP was considered when MRSA was isolated from a tracheal aspirate or bronchoalveolar lavage. Clinical success was evaluated by assessing improvement or resolution of signs and symptoms of VAP by day 14. After matching on confounding factors, logistic regression models were used to determine if an association existed between treatment arm and clinical success.ResultsA total of 188 patients were evaluated (101 treated with linezolid and 87 with vancomycin). The mean ± standard deviation Acute Physiology and Chronic Health Evaluation (APACHE) II score was 21 ± 11 for linezolid- and 19 ± 9 for vancomycin-treated patients (P = 0.041). Clinical success occurred in 85% of linezolid-treated patients compared with 69% of vancomycin-treated patients (P = 0.009). After adjusting for confounding factors, linezolid-treated patients were 24% more likely to experience clinical success than vancomycin-treated patients (P = 0.018).ConclusionsThis study adds to the evidence indicating that patients with MRSA VAP who are treated with linezolid are more likely to respond favorably compared with patients treated with vancomycin.

Development and implementation of a performance improvement project in adult intensive care units: overview of the Improving Medicine Through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia (IMPACT-HAP) study

IntroductionIn 2005 the American Thoracic Society and Infectious Diseases Society of America (ATS/IDSA) published guidelines for managing hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and healthcare-associated pneumonia (HCAP). Although recommendations were evidence based, collective guidelines had not been validated in clinical practice and did not provide specific tools for local implementation. We initiated a performance improvement project designated Improving Medicine Through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia (IMPACT-HAP) at four academic centers in the United States. Our objectives were to develop and implement the project, and to assess compliance with quality indicators in adults admitted to intensive care units (ICUs) with HAP, VAP, or HCAP.MethodsThe project was conducted in three phases over 18 consecutive months beginning 1 February 2006: 1) a three-month planning period for literature review to create the consensus pathway for managing nosocomial pneumonia in these ICUs, a data collection form, quality performance indicators, and internet-based repository; 2) a six-month implementation period for customizing ATS/IDSA guidelines into center-specific guidelines via educational forums; and 3) a nine-month post-implementation period for continuing education and data collection. Data from the first two phases were combined (pre-implementation period) and compared with data from the post-implementation period.ResultsWe developed a consensus pathway based on ATS/IDSA guidelines and customized it at the local level to accommodate formulary and microbiologic considerations. We implemented multimodal educational activities to teach ICU staff about the guidelines and continued education throughout post-implementation. We registered 432 patients (pre- vs post-implementation, 274 vs 158). Diagnostic criteria for nosocomial pneumonia were more likely to be met during post-implementation (247/257 (96.1%) vs 150/151 (99.3%); P = 0.06). Similarly, empiric antibiotics were more likely to be compliant with ATS/IDSA guidelines during post-implementation (79/257 (30.7%) vs 66/151 (43.7%); P = 0.01), an effect that was sustained over quarterly intervals (P = 0.0008). Between-period differences in compliance with obtaining cultures and use of de-escalation were not statistically significant.ConclusionsDeveloping a multi-center performance improvement project to operationalize ATS/IDSA guidelines for HAP, VAP, and HCAP is feasible with local consensus pathway directives for implementation and with quality indicators for monitoring compliance with guidelines.

Evaluation of intravenous voriconazole in patients with compromised renal function

BackgroundIncorporation of the solubilizing excipient, sulfobutylether-β-cyclodextrin (SBECD), in the intravenous (IV) formulation of voriconazole has resulted in the recommendation that this formulation be used with caution in patients with creatinine clearances (Clcr) < 50 mL/min. This study evaluated the safety of IV voriconazole compared with two other IV antifungals not containing SBECD in patients with compromised renal function.MethodsA total of 128 patients aged 11–93 years who had a baseline Clcr < 50 mL/min between January 1, 2007 and December 31, 2010 were identified from a database of a university-affiliated inpatient healthcare system; of these, 55 patients received caspofungin, 54 patients received fluconazole, and 19 patients received voriconazole. Changes in serum creatinine (Scr) and Clcr levels while on therapy were compared with baseline values and between groups.ResultsThe groups had similar characteristics apart from the larger proportion of females that received fluconazole. Baseline Scr was higher in those receiving caspofungin, but maximal increases of Scr and decreases in Clcr were greatest for the fluconazole group. Acute kidney injury (AKI), assessed by RIFLE criteria, was more frequent in the fluconazole vs. the caspofungin group (p < 0.01); incidence of AKI in the voriconazole group was not significantly different than found in the other two groups. The infecting organism was a predictor of AKI and formulation with SBECD was not.ConclusionsTreatment of fungal infections in patients with compromised renal function with an SBECD-containing antifungal agent was not associated with AKI in clinical practice. Since the infecting organism was associated with AKI, decision on which antifungal to use should be determined by susceptibilities to the organism and not the incorporation of SBECD in the IV formulation.

Absence of gender-based differences in outcome of patients with hospital-acquired pneumonia.

BACKGROUND The objective of this analysis was to evaluate the association between gender and clinical outcomes in intensive care unit (ICU) patients with hospital-acquired pneumonia (HAP) since data thus far are controversial. METHODS Data from a convenience sample of ICU patients with HAP, including ventilator-associated and health care-associated pneumonia, were retrospectively collected from four academic institutions (Improving Medicine through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia [IMPACT-HAP] study). Outcomes included 28-day mortality, clinical failure at day 14, hospital and ICU length of stay (LOS), and duration of mechanical ventilation. We compared baseline characteristics and performed multivariate analysis to identify factors independently associated with mortality. RESULTS Among 416 patients, 271 were men and 145 were women. Women were older (62.4±16.9 vs. 55.7±16.5 years, p<0.001) and more critically ill, with Acute Physiology and Chronic Health Evaluation (APACHE) II scores of 21 vs. 19 (p=0.004). Day-28 mortality was 30% for women and 24% for men (p=0.25). Increased 28-day mortality was associated with severity of illness, age, ventilator-associated pneumonia, vascular disease, and hospital LOS prior to pneumonia diagnosis. No significant differences were found in the distribution of bacteria pathogens or in clinical failure rates (36% vs. 31%) between genders. Duration in days of mechanical ventilation, ICU LOS and hospital LOS after the diagnosis of pneumonia were not significantly different between men and women. Analyzing data for women based on presumed pre- or postmenopausal status (age breakpoint of 50 years), showed an increased in ICU LOS (15 vs. 25 days; p=0.0026) and hospital LOS (22 vs. 30 days; p=0.05) for women ≤50 years. No differences were noted in 28-day mortality (24.3% vs. 13.1%; p=0.18) in women ≤50 years of age. CONCLUSIONS In ICU patients with pneumonia, female gender was not associated with worse outcomes or increased resource utilization compared to male gender. Further studies are needed to evaluate menopausal status and outcomes in women with pneumonia.

Invasive Aspergillus infections in hospitalized patients with chronic lung disease

Background Although invasive pulmonary aspergillosis (IPA) is more prevalent in immunocompromised patients, critical care clinicians need to be aware of the occurrence of IPA in the nontraditional host, such as a patient with chronic lung disease. The purpose of this study was to describe the IPA patient with chronic lung disease and compare the data with that of immunocompromised patients. Methods The records of 351 patients with Aspergillus were evaluated in this single-center, retrospective study for evidence and outcomes of IPA. The outcomes of 57 patients with chronic lung disease and 56 immunocompromised patients were compared. Patients with chronic lung disease were defined by one of the following descriptive terms: emphysema, asthma, idiopathic lung disease, bronchitis, bronchiectasis, sarcoid, or pulmonary leukostasis. Results Baseline demographics were similar between the two groups. Patients with chronic lung disease were primarily defined by emphysema (61%) and asthma (18%), and immunocompromised patients primarily had malignancies (27%) and bone marrow transplants (14%). A higher proportion of patients with chronic lung disease had a diagnosis of IPA by bronchoalveolar lavage versus the immunocompromised group (P < 0.03). The major risk factors for IPA were found to be steroid use in the chronic lung disease group and neutropenia and prior surgical procedures in the immunocompromised group. Overall, 53% and 69% of chronic lung disease and immunocompromised patients were cured (P = 0.14); 55% of chronic lung patients and 47% of immunocompromised patients survived one month (P = 0.75). Conclusion Nontraditional patients with IPA, such as those with chronic lung disease, have outcomes and mortality similar to that in the more traditional immunocompromised population.

Understanding why low-risk patients accept vaccines: a socio-behavioral approach.

BackgroundVaccines are one of the most important public health interventions. Understanding factors associated with vaccine acceptance is critical. The objectives of this study were to evaluate the impact of the three constructs of the Theory of Planned Behavior (TPB) on the intention to be vaccinated among healthy individuals being seen for pre-travel care, and to evaluate if behavioral intention was associated with vaccine acceptance.MethodsWe surveyed individuals seeking vaccination at the University of Louisville Vaccine and International Health and Travel Clinic. Linear and two stage least squares regression models were used to define the associations between constructs of the TPB and the intention to be vaccinated, as well as the association between the intention to be vaccinated and vaccine acceptance.ResultsA total of 183 individuals were included in the analysis. None of the constructs of the TPB were associated with intention to be vaccinated. Behavioral intention was not associated with vaccination acceptance.ConclusionsThis study suggests that the TPB does not predict the intention to get vaccinated among individuals attending our Vaccine and International Health and Travel Clinic. It will be critical to define better predictors of vaccine uptake in healthy, low-risk individuals to increase vaccine acceptance.

Incidence of Intravenous Catheter-Site Complications in Patients Treated With Linezolid or Vancomycin for Skin Infections Caused by Methicillin-Resistant Staphylococcus aureus

Objective The aim of the study was to compare all-cause adverse events (AEs) and those caused by intravenous (IV) catheter-site complications (IVCSCs) using data from a previously published study of the use of linezolid or vancomycin for treatment of complicated skin and skin structure infections (cSSSI) suspected or proven to be caused by methicillin-resistant Staphylococcus aureus. Methods To examine the incidence of AEs caused by the 2 antibiotic treatments, we conducted a post hoc analysis of data from a prospective, open-label, randomized, multicenter phase 4 study. Patients were randomized to treatment with either oral (PO) or IV linezolid 600 mg every 12 hours or with IV vancomycin 15 mg/kg every 12 hours with dose adjustment as needed. Study treatment was administered for 7 to 14 days. We excluded patients with baseline bacteremia (n = 11) and those who started on PO linezolid (n = 215). We analyzed data only from patients who received at least 1 dose of IV study medication. Results Patient demographics and types of cSSSI were comparable among patients receiving linezolid (n = 315) and vancomycin (n = 511). Mean durations of IV therapy for patients receiving linezolid and vancomycin were 4.5 days and 7.6 days (1,418 and 3,884 patient-days, respectively). All-cause AEs were reported in 50% and 51% of patients in the linezolid and vancomycin groups, respectively; all-cause IVCSCs were reported in 2% and 7%, respectively. Treatment-related IVCSCs were reported in 1 patient in the linezolid group and 16 patients in the vancomycin group. Conclusions The overall rate of AEs was similar among patients receiving linezolid and vancomycin, but AEs caused by IVCSCs were more frequent among patients receiving vancomycin and rare episodes of bacteremia and sepsis were more common in the linezolid group.

The Changing Epidemiology of Invasive Aspergillosis in the Non-Traditional Host: Risk Factors and Outcomes

Background: Invasive fungal infections due to Aspergillus spp. are common in ‘high-risk’ immunocompromised patients. Recently, invasive aspergillosis (IA) in the ‘low-risk’ or ‘non-traditional’ host has been increasingly recognized. Unfortunately, risk factors and diagnostic modalities for this infection are poorly described. This study’s goal is to further characterize IA in the population classically described as ‘low-risk’ and infrequently studied. Methods: A retrospective cohort of patients with proven or probable IA (excluding those with neutropenia or hematologic malignancy) was evaluated. Results: Thirty-six patients with either proven (23) or probable (13) IA met inclusion criteria. Mean age was 54.6 years. The most common risk factors identified in patients with IA were steroid use (69%), ICU stay (56%), immunosuppressive agents (39%), solid organ transplant (33%), diabetes (28%) and mechanical ventilation (28%). The most common sites of infection were lungs (67%) and sinuses (19%). A. fumigatus was the most prevalent spp. isolated (63%), followed by A. niger (16%). Additionally, 17 patients had bacterial coinfections. Voriconazole was the first-line antifungal used in 23 patients, followed by combination antifungal therapy in eight patients. Clinical success was noted in 72% of patients with a 25% cumulative mortality 90 days after diagnosis. Conclusions: This study describes IA in a population infrequently studied and considered to be at low risk when compared to the neutropenic population of patients. Awareness of risk factors in this ‘non-traditional’ host, improved diagnostic techniques, and earlier initiation of appropriate antifungal therapy should improve overall survival and response to therapy. Larger, multicenter epidemiologic studies in similar populations are warranted to improve the understanding of this underestimated infection. Correspondence to: Jose A Vazquez MD, Division of Infectious Diseases, Medical College of Georgia/Augusta University, 1120 15th Street, Room 3029, Augusta, GA 30912, USA, Tel: +1 706-721-1244; Fax: +1 706-721-4517; E-mail: jvazquez@augusta.edu