Glenn Wortmann

Nephrotoxicity Associated with Intravenous Colistin (Colistimethate Sodium) Treatment at a Tertiary Care Medical Center

The incidence of acute renal failure, defined by the risk, injury, or failure criteria of the RIFLE criteria (risk, injury, failure, loss, and end-stage kidney disease), in 66 patients who received colistimethate sodium was 45%, and 21% of patients stopped therapy because of nephrotoxicity. The RIFLE criteria should be used in the future to allow for comparison of nephrotoxicity among studies.

Old world leishmaniasis: an emerging infection among deployed US military and civilian workers.

Many veterans of Operation Iraqi Freedom are now returning to the United States after potential exposure to leishmaniasis. In the past year, large numbers of leishmaniasis cases of a magnitude not encountered in the United States since World War II have challenged clinicians in both the military and the civilian sectors. Many Reserve and National Guard troops were deployed to Iraq and are now back in their communities. Hundreds of leishmaniasis cases, which were managed by a few practitioners initially, permitted further appreciation of the epidemiology and diagnostic and treatment options for Old World leishmaniasis. We describe the current situation, with on-the-ground experience, complimented by a literature review, and we provide a practical list of options for the clinician likely to encounter this parasitic infection in the coming months and years.

Safety and Efficacy of Intravenous Sodium Stibogluconate in the Treatment of Leishmaniasis: Recent U.S. Military Experience

The efficacy and toxicity of sodium stibogluconate (SSG) at a dosage of 20 mg/(kg.d) for either 20 days (for cutaneous disease) or 28 days (for visceral, mucosal, or viscerotropic disease) in the treatment of leishmaniasis is reported. Ninety-six U.S. Department of Defense health care beneficiaries with parasitologically confirmed leishmaniasis were prospectively followed for 1 year. One patient was infected with human immunodeficiency virus; otherwise, comorbidity was absent. Clinical cure occurred in 91% of 83 cases of cutaneous disease and 93% of 13 cases of visceral/viscerotropic disease. Adverse effects were common and necessitated interruption of treatment in 28% of cases, but they were generally reversible. These included arthralgias and myalgias (58%), pancreatitis (97%), transaminitis (67%), headache (22%), hematologic suppression (44%), and rash (9%). No subsequent mucosal leishmaniasis was identified, and there were no deaths attributable to SSG or leishmaniasis.

Emergence of Colistin-Resistance in Extremely Drug-Resistant Acinetobacter baumannii Containing a Novel pmrCAB Operon During Colistin Therapy of Wound Infections

BACKGROUND Colistin resistance is of concern since it is increasingly needed to treat infections caused by bacteria resistant to all other antibiotics and has been associated with poorer outcomes. Longitudinal data from in vivo series are sparse. METHODS Under a quality-improvement directive to intensify infection-control measures, extremely drug-resistant (XDR) bacteria undergo phenotypic and molecular analysis. RESULTS Twenty-eight XDR Acinetobacter baumannii isolates were longitudinally recovered during colistin therapy. Fourteen were susceptible to colistin, and 14 were resistant to colistin. Acquisition of colistin resistance did not alter resistance to other antibiotics. Isolates had low minimum inhibitory concentrations of an investigational aminoglycoside, belonged to multi-locus sequence type 94, were indistinguishable by pulsed-field gel electrophoresis and optical mapping, and harbored a novel pmrC1A1B allele. Colistin resistance was associated with point mutations in the pmrA1 and/or pmrB genes. Additional pmrC homologs, designated eptA-1 and eptA-2, were at distant locations from the operon. Compared with colistin-susceptible isolates, colistin-resistant isolates displayed significantly enhanced expression of pmrC1A1B, eptA-1, and eptA-2; lower growth rates; and lowered fitness. Phylogenetic analysis suggested that colistin resistance emerged from a single progenitor colistin-susceptible isolate. CONCLUSIONS We provide insights into the in vivo evolution of colistin resistance in a series of XDR A. baumannii isolates recovered during therapy of infections and emphasize the importance of antibiotic stewardship and surveillance.

Prevention of infections associated with combat-related extremity injuries

During combat operations, extremities continue to be the most common sites of injury with associated high rates of infectious complications. Overall, ∼ 15% of patients with extremity injuries develop osteomyelitis, and ∼ 17% of those infections relapse or recur. The bacteria infecting these wounds have included multidrug-resistant bacteria such as Acinetobacter baumannii, Pseudomonas aeruginosa, extended-spectrum β-lactamase-producing Klebsiella species and Escherichia coli, and methicillin-resistant Staphylococcus aureus. The goals of extremity injury care are to prevent infection, promote fracture healing, and restore function. In this review, we use a systematic assessment of military and civilian extremity trauma data to provide evidence-based recommendations for the varying management strategies to care for combat-related extremity injuries to decrease infection rates. We emphasize postinjury antimicrobial therapy, debridement and irrigation, and surgical wound management including addressing ongoing areas of controversy and needed research. In addition, we address adjuvants that are increasingly being examined, including local antimicrobial therapy, flap closure, oxygen therapy, negative pressure wound therapy, and wound effluent characterization. This evidence-based medicine review was produced to support the Guidelines for the Prevention of Infections Associated With Combat-Related Injuries: 2011 Update contained in this supplement of Journal of Trauma.

Infectious complications of damage control orthopedics in war trauma.

BACKGROUND War-trauma, especially due to blast injury, can be associated with long bone fracture. Immediate external fixation of fractures, followed by internal fixation when the patient is medically stabilized (damage control orthopedics [DCO]), is the U.S. Army policy for war-related fractures. Data on infectious outcomes when DCO is used for war-trauma fractures are scant. METHODS A retrospective review of U.S. war-trauma patients from 2003 to 2007 with femoral or tibial fractures treated by DCO was conducted. Fishers Exact and Mann-Whitney tests were used for comparisons. RESULTS Fifty-eight soldiers were identified. Fifty-five were males with a median age of 26 years (19-54 years) and a median time to internal fixation by intramedually nailing of 9 days (4-414 days). Eighty-eight percent of fractures were open, and 57% were femoral fractures. The median duration of follow-up was 447 days (20-1,340 days). Fracture site infection occurred in 40% (23 of 58), with suspected osteomyelitis in 17% (10 of 58). Of infected nails, fracture union occurred in 70% and nail retention in 57%. Median time to infection after nail placement was 15 days (0-717 days) with 75% of infections occurring by day 113. Multiple bacterial pathogens including Acinetobacter baumannii and Staphylococcus spp. were causative organisms. Blast injuries occurred in 91% of infected versus 47% of uninfected (p = 0.005). There was no difference between infections occurring in femoral (61%) versus tibial (39%) (p = 0.620) location. CONCLUSIONS Infection was associated with 40% of DCO-associated intramedullary nails. Blast injury was a predictor of infection. Despite infection, fracture union and nail retention rates were high, suggesting a good outcome.

Lipsosomal Amphotericin B for Treatment of Cutaneous Leishmaniasis

Treatment options for cutaneous leishmaniasis in the United States are problematic because the available products are either investigational, toxic, and/or of questionable effectiveness. A retrospective review of patients receiving liposomal amphotericin B through the Walter Reed Army Medical Center for the treatment of cutaneous leishmaniasis during 2007-2009 was conducted. Twenty patients who acquired disease in five countries and with five different strains of Leishmania were treated, of whom 19 received a full course of treatment. Sixteen (84%) of 19 experienced a cure with the initial treatment regimen. Three patients did not fully heal after an initial treatment course, but were cured with additional dosing. Acute infusion-related reactions occurred in 25% and mild renal toxicity occurred in 45% of patients. Although the optimum dosing regimen is undefined and the cost and toxicity may limit widespread use, liposomal amphotericin B is a viable treatment alternative for cutaneous leishmaniasis.

A Randomized, Double-Blind Study of the Efficacy of a 10- or 20-Day Course of Sodium Stibogluconate for Treatment of Cutaneous Leishmaniasis in United States Military Personnel

The recommended treatment for cutaneous leishmaniasis is pentavalent antimony at a dosage of 20 mg/kg/day for 20 days. Some studies conducted in locales in which Leishmania is endemic have suggested that shorter courses of treatment may be as efficacious. We conducted a randomized, double-blind, placebo-controlled study of 10 versus 20 days of sodium stibogluconate (SSG) in United States military personnel who contracted cutaneous leishmaniasis while serving overseas; 19 patients received SSG for 10 days (and placebo for 10 days), and 19 patients received SSG for 20 days. Cure rates were 100% (19 of 19 patients) in the 10-day group and 95% (18 of 19 patients) in the 20-day group. Side effects were more common among patients who received 20 days of therapy. In this group of otherwise healthy young adults, SSG at a dosage of 20 mg/kg/day for 10 days appears to have been therapeutically equivalent and less toxic than the standard 20-day course.

Outcomes of highly active antiretroviral therapy in the context of universal access to healthcare: the U.S. Military HIV Natural History Study

BackgroundTo examine the outcomes of highly-active antiretroviral therapy (HAART) for individuals with free access to healthcare, we evaluated 2327 patients in a cohort study composed of military personnel and beneficiaries with HIV infection who initiated HAART from 1996 to the end of 2007.MethodsOutcomes analyzed were virologic suppression (VS) and failure (VF), CD4 count changes, AIDS and death. VF was defined as never suppressing or having at least one rebound event. Multivariate (MV) analyses stratified by the HAART initiation year (before or after 2000) were performed to identify risk factors associated with these outcomes.ResultsAmong patients who started HAART after 2000, 81% had VS at 1 year (N = 1,759), 85% at 5 years (N = 1,061), and 82% at 8 years (N = 735). Five years post-HAART, the median CD4 increase was 247 cells/ml and 34% experienced VF. AIDS and mortality rates at 5 years were 2% and 0.3%, respectively. In a MV model adjusted for known risk factors associated with treatment response, being on active duty (versus retired) at HAART initiation was associated with a decreased risk of AIDS (HR = 0.6, 95% CI 0.4-1.0) and mortality (0.6, 0.3-0.9), an increased probability of CD4 increase ≥ 50% (1.2, 1.0-1.4), but was not significant for VF.ConclusionsIn this observational cohort, VS rates approach those described in clinical trials. Initiating HAART on active duty was associated with even better outcomes. These findings support the notion that free access to healthcare likely improves the response to HAART thereby reducing HIV-related morbidity and mortality.

Multidrug-resistant bacterial colonization of combat-injured personnel at admission to medical centers after evacuation from Afghanistan and Iraq.

BACKGROUND Multidrug-resistant organism (MDRO) infections, including those secondary to Acinetobacter (ACB) and extended spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (Escherichia coli and Klebsiella species) have complicated the care of combat-injured personnel during Operations Iraqi Freedom and Enduring Freedom. Data suggest that the source of these bacterial infections includes nosocomial transmission in both deployed hospitals and receiving military medical centers (MEDCENs). Admission screening for MDRO colonization has been established to monitor this problem and effectiveness of responses to it. METHODS Admission colonization screening of injured personnel began in 2003 at the three US-based MEDCENs receiving the majority of combat-injured personnel. This was extended to Landstuhl Regional Medical Center (LRMC; Germany) in 2005. Focused on ACB initially, screening was expanded to include all MDROs in 2009 with a standardized screening strategy at LRMC and US-based MEDCENs for patients evacuated from the combat zone. RESULTS Eighteen thousand five hundred sixty of 21,272 patients admitted to the 4 MEDCENs in calendar years 2005 to 2009 were screened for MDRO colonization. Average admission ACB colonization rates at the US-based MEDCENs declined during this 5-year period from 21% (2005) to 4% (2009); as did rates at LRMC (7-1%). In the first year of screening for all MDROs, 6% (171 of 2,989) of patients were found colonized at admission, only 29% (50) with ACB. Fifty-seven percent of patients (98) were colonized with ESBL-producing E. coli and 11% (18) with ESBL-producing Klebsiella species. CONCLUSIONS Although colonization with ACB declined during the past 5 years, there seems to be replacement of this pathogen with ESBL-producing Enterobacteriaceae.