Duane R. Hospenthal

Methicillin-Resistant Staphylococcus aureus (MRSA) Nares Colonization at Hospital Admission and Its Effect on Subsequent MRSA Infection

BACKGROUND Asymptomatic colonization with methicillin-resistant Staphylococcus aureus (MRSA) has been described as a risk factor for subsequent MRSA infection. MRSA is an important nosocomial pathogen but has currently been reported in patients without typical risk factors for nosocomial acquisition. This study was designed to evaluate the impact of asymptomatic nares MRSA colonization on the development of subsequent MRSA infection. The incidence of MRSA infection was examined in patients with and patients without MRSA or methicillin-susceptible S. aureus (MSSA) colonization at admission to the hospital and in those who developed colonization during hospitalization. METHODS Patients admitted to 5 representative hospital units were prospectively evaluated. Nares samples were obtained for culture at admission and during hospitalization. Laboratory culture results were monitored to identify all MRSA infections that occurred during the study period and 1 year thereafter. RESULTS Of the 758 patients who had cultures of nares samples performed at admission, 3.4% were colonized with MRSA, and 21% were colonized with MSSA. A total of 19% of patients with MRSA colonization at admission and 25% who acquired MRSA colonization during hospitalization developed infection with MRSA, compared with 1.5% and 2.0% of patients colonized with MSSA (P<.01) and uncolonized (P<.01), respectively, at admission. MRSA colonization at admission increased the risk of subsequent MRSA infection, compared with MSSA colonization (relative risk [RR], 13; 95% confidence interval [CI], 2.7-64) or no staphylococcal colonization (RR, 9.5; 95% CI, 3.6-25) at admission. Acquisition of MRSA colonization also increased the risk for subsequent MRSA infection, compared with no acquisition (RR, 12; 95% CI, 4.0-38). CONCLUSION MRSA colonization of nares, either present at admission to the hospital or acquired during hospitalization, increases the risk for MRSA infection. Identifying MRSA colonization at admission could target a high-risk population that may benefit from interventions to decrease the risk for subsequent MRSA infection.

Natural History of Community-Acquired Methicillin-Resistant Staphylococcus aureus Colonization and Infection in Soldiers

BACKGROUND Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging pathogen for which the prevalence, risk factors, and natural history are incompletely understood. METHODS In this prospective observational study, we evaluated 812 US Army soldiers to determine the prevalence of and risk factors for CA-MRSA colonization and the changes in colonization rate over time, as well as to determine the clinical significance of CA-MRSA colonization. Demographic data and swab samples from the nares for S. aureus cultures were obtained from participants at the start of their training and 8-10 weeks later. Over this time period, participants were observed prospectively to monitor for soft-tissue infections. S. aureus isolates were characterized by in vitro examination of antibiotic susceptibilities, mecA confirmation, pulsed-field gel electrophoresis, and Panton-Valentine leukocidin (PVL) gene testing. RESULTS At the initial sampling, 24 of the participants (3%) were colonized with CA-MRSA, 9 of whom (38%) developed soft-tissue infections during the study period. In contrast, 229 participants (28%) were colonized with methicillin-susceptible S. aureus (MSSA), 8 (3%) of whom developed clinical infections during the same period (relative risk, 10.7; 95% confidence interval, 4.6-25.2; P<.001). At follow-up culture, the CA-MRSA colonization rate dropped to 1.6% without eradication efforts. Previous antibiotic use was a risk factor for CA-MRSA colonization at the initial sampling (P=.03). PVL genes were detected in 66% of 45 recovered CA-MRSA isolates, including all 9 clinical isolates available for analysis. Of subjects hospitalized, 5 of 6 had PVL-positive CA-MRSA infections. CONCLUSIONS CA-MRSA colonization with PVL-positive strains was associated with a significant risk of soft-tissue infection, suggesting that CA-MRSA may be more virulent than MSSA. Previous antibiotic use may play a role in CA-MRSA colonization.

Infectious Complications of Open Type III Tibial Fractures among Combat Casualties

BACKGROUND Combat is associated with high-energy explosive injuries, often resulting in open tibial fractures complicated by nonunion and infection. We characterize the infections seen in conjunction with combat-associated type III tibial fractures. METHODS We performed a retrospective medical records review to identify US military service members wounded in Iraq or Afghanistan with open diaphyseal tibial fractures who were admitted to our facility (Brooke Army Medical Center, Fort Sam Houston, Texas) between March 2003 and September 2006. RESULTS Of the 62 patients with open tibial fractures who were identified in our initial search, 40 had fractures that met our inclusion criteria as type III diaphyseal tibial fractures. Three patients were excluded because their fractures were managed with early limb amputation, and 2 were excluded because of incomplete follow-up records. Twenty-seven of these 35 patients had at least 1 organism present in initial deep-wound cultures that were performed at admission to the hospital. The pathogens that were identified most frequently were Acinetobacter, Enterobacter species, and Pseudomonas aeruginosa. Thirteen of the 35 patients had union times of >9 months that appeared to be associated with infection. None of the gram-negative bacteria identified in the initial wound cultures were recovered again at the time of a second operation; however, all patients had at least 1 staphylococcal organism. One patient had an organism present during initial culture and in the nonunion wound; this organism was a methicillin-resistant Staphylococcus aureus strain that was inadvertently not treated. Five of 35 patients ultimately required limb amputation, with infectious complications cited as the reason for amputation in 4 of these cases. CONCLUSIONS Combat-associated type III tibial fractures are predominantly associated with infections due to gram-negative organisms, and these infections are generally successfully treated. Recurrent infections are predominantly due to staphylococci.

Epidemiology of Staphylococcus aureus blood and skin and soft tissue infections in the US military health system, 2005-2010.

CONTEXT Rates of hospital-onset methicillin-resistant Staphylococcus aureus (MRSA) infections are reported as decreasing, but recent rates of community-onset S. aureus infections are less known. OBJECTIVES To characterize the overall and annual incidence rates of community-onset and hospital-onset S. aureus bacteremia and skin and soft tissue infections (SSTIs) in a national health care system and to evaluate trends in the incidence rates of S. aureus bacteremia and SSTIs and the proportion due to MRSA. DESIGN, SETTING, AND PARTICIPANTS Observational study of all Department of Defense TRICARE beneficiaries from January 2005 through December 2010. Medical record databases were used to identify and classify all annual first-positive S. aureus blood and wound or abscess cultures as methicillin-susceptible S. aureus or MRSA, and as community-onset or hospital-onset infections (isolates collected >3 days after hospital admission). MAIN OUTCOME MEASURES Unadjusted incidence rates per 100,000 person-years of observation, the proportion of infections that was due to MRSA, and annual trends for 2005 through 2010 (examined using the Spearman rank correlation test or the Mantel-Haenszel χ2 test for linear trend). RESULTS During 56 million person-years (nonactive duty: 47 million person-years; active duty: 9 million person-years), there were 2643 blood and 80,281 wound or abscess annual first-positive S. aureus cultures. Annual incidence rates varied from 3.6 to 6.0 per 100,000 person-years for S. aureus bacteremia and 122.7 to 168.9 per 100,000 person-years for S. aureus SSTIs. The annual incidence rates for community-onset MRSA bacteremia decreased from 1.7 per 100,000 person-years (95% CI, 1.5-2.0 per 100,000 person-years) in 2005 to 1.2 per 100,000 person-years (95% CI, 0.9-1.4 per 100,000 person-years) in 2010 (P = .005 for trend). The annual incidence rates for hospital-onset MRSA bacteremia also decreased from 0.7 per 100,000 person-years (95% CI, 0.6-0.9 per 100,000 person-years) in 2005 to 0.4 per 100,000 person-years (95% CI, 0.3-0.5 per 100,000 person-years) in 2010 (P = .005 for trend). Concurrently, the proportion of community-onset SSTI due to MRSA peaked at 62% in 2006 before decreasing annually to 52% in 2010 (P < .001 for trend). CONCLUSION In the Department of Defense population consisting of men and women of all ages from across the United States, the rates of both community-onset and hospital-onset MRSA bacteremia decreased in parallel, while the proportion of community-onset SSTIs due to MRSA has more recently declined.

Bacteriology of War Wounds at the Time of Injury

Bacterial contamination of war wounds occurs either at the time of injury or during the course of therapy. Characterization of the bacteria recovered at the time of initial trauma could influence the selection of empiric antimicrobial agents used to prevent infection. In the spring of 2004, U.S. military casualties who presented to the 31st Combat Support Hospital in Baghdad, Iraq, with acute traumatic injuries resulting in open wounds underwent aerobic culture of their wounds to identify the bacteria colonizing the wounds. Forty-nine casualties with 61 separate wounds were evaluated. Wounds were located predominantly in the upper and lower extremities and were primarily from improvised explosive devices or mortars. Thirty wounds (49%) had bacteria recovered on culture, with 40 bacteria identified. Eighteen casualties (20 wounds) had undergone field medical therapy (irrigation and/or antimicrobial treatment); six of these had nine bacterial isolates on culture. Of the 41 wounds from 31 patients who had received no previous therapy, 24 grew 31 bacteria. Gram-positive bacteria (93%), mostly skin-commensal bacteria, were the predominant organisms identified. Only three Gram-negative bacteria were detected, none of which were characterized as broadly resistant to antimicrobial agents. The only resistant bacteria recovered were two isolates of methicillin-resistant Staphylococcus aureus (MRSA). Our assessment of war wound bacterioly soon after injury reveals a predominance of Gram-positive organisms of low virulence and pathogenicity. The presence of MRSA in wounds likely reflects the increasing incidence of community-acquired MRSA bacteria. These data suggest that the use of broad-spectrum antibiotics with efficacy against more resistant, Gram-negative bacteria, such as Pseudomonas aeruginosa and Acinetobacter spp., is unnecessary in early wound management.

Prevalence of multidrug-resistant organisms recovered at a military burn center §

Infections caused by multidrug-resistant (MDR) pathogens are associated with significant morbidity and mortality in patients with burn injuries. We performed a 6-year antibiotic susceptibility records review from January 2003 to December 2008 to assess the prevalence of MDR isolates by pathogen at the US Army Institute of Surgical Research Burn Center. During the study period Acinetobacter baumannii (780 isolates [22%]) was the most prevalent organism recovered, followed by Pseudomonas aeruginosa (703 isolates [20%]), Klebsiella pneumoniae (695 isolates [20%]), and Staphylococcus aureus (469 isolates [13%]). MDR prevalence rates among these isolates were A. baumannii 53%, methicillin-resistant S. aureus (MRSA) 34%, K. pneumoniae 17% and P. aeruginosa 15%. Two isolates, 1 A. baumannii and 1 P. aeruginosa, were identified as resistant to all 4 classes of antibiotics tested plus colistin. A. baumannii isolates recovered from patients with burns greater than 30% of total body surface area (TBSA) were more likely to be MDR (61%) with no significant difference for P. aeruginosa and K. pneumoniae. A higher proportion of MDR P. aeruginosa isolates were recovered from respiratory specimens compared to blood specimens (24% vs. 9%) while the opposite was true for MRSA (35% vs. 54%). A comparison of A. baumannii recovered during hospitalization days 1-5 and 15-30 revealed higher MDR levels as length of stay increased (48% vs. 75%) while no significant trends were observed for P. aeruginosa and K. pneumoniae. A similar pattern was observed for MDR A. baumannii levels for the facility between 2003 and 2005 and 2006-2008 (39% vs. 70%), with no significant increase in MDR P. aeruginosa and MDR K. pneumoniae. Increasing antibiotic resistance patterns of the most prevalent isolates recovered during extended hospitalization, impact of % TBSA and other clinical parameters may affect empirical antimicrobial therapy and patient management decisions during treatment.

Targeted Intranasal Mupirocin To Prevent Colonization and Infection by Community-Associated Methicillin-Resistant Staphylococcus aureus Strains in Soldiers: a Cluster Randomized Controlled Trial

ABSTRACT Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging pathogen that primarily manifests as uncomplicated skin and soft tissue infections. We conducted a cluster randomized, double-blind, placebo-controlled trial to determine whether targeted intranasal mupirocin therapy in CA-MRSA-colonized soldiers could prevent infection in the treated individual and prevent new colonization and infection within their study groups. We screened 3,447 soldiers comprising 14 training classes for CA-MRSA colonization from January to December 2005. Each training class was randomized to either the mupirocin or placebo study group, and the participants identified as CA-MRSA colonized were treated with either mupirocin or placebo. All participants underwent repeat screening after 8 to 10 weeks and were monitored for 16 weeks for development of infection. Of 3,447 participants screened, 134 (3.9%) were initially colonized with CA-MRSA. Five of 65 (7.7%; 95% confidence interval [95% CI], 4.0% to 11.4%) placebo-treated participants and 7 of 66 (10.6%; 95% CI, 7.9% to 13.3%) mupirocin-treated participants developed infections; the difference in the infection rate of the placebo- and mupirocin-treated groups was −2.9% (95% CI, −7.5% to 1.7%). Of those not initially colonized with CA-MRSA, 63 of 1,459 (4.3%; 95% CI, 2.7% to 5.9%) of the placebo group and 56 of 1,607 (3.5%; 95% CI, 2.6% to 5.2%) of the mupirocin group developed infections; the difference in the infection rate of the placebo and mupirocin groups was 0.8% (95% CI, −1.0% to 2.7%). Of 3,447 participants, 3,066 (89%) were available for the second sampling and completed follow-up. New CA-MRSA colonization occurred in 24 of 1,459 (1.6%; 95% CI, 0.05% to 2.8%) of the placebo group participants and 23 of 1,607 (1.4%; 95% CI, 0.05% to 2.3%) of the mupirocin group participants; the difference in the infection rate of the placebo and mupirocin groups was 0.2% (95% CI, −1.3% to 1.7%). Despite CA-MRSA eradication in colonized participants, this study showed no decrease in infections in either the mupirocin-treated individuals or within their study group. Furthermore, CA-MRSA eradication did not prevent new colonization within the study group.

Direct Comparison of the BACTEC 9240 and BacT/ALERT 3D Automated Blood Culture Systems for Candida Growth Detection

ABSTRACT A direct comparison of two automated blood culture systems was conducted to compare their ability to detect Candida growth. The systems evaluated were the BACTEC 9240 (Bactec) and BacT/ALERT 3D (BacT). The aerobic, anaerobic, and mycology media for each system were evaluated: Bactec Plus Aerobic/F, Plus Anaerobic/F, and Myco/F Lytic bottles,, respectively, and BacT FA, SN, and MB bottles, respectively. Each blood culture bottle was inoculated with fresh blood from healthy donors. Fifty isolates of Candida spp. were used. The six different blood culture bottles were each inoculated with 1,000 yeasts per bottle and then incubated in the corresponding automated system. The BacT detected growth of 90% (135 of 150) of Candida pathogens, while Bactec detected 66% (100 of 150). Growth was detected in all BacT and Bactec mycology bottles, all BacT aerobic bottles, and by terminal subculture of all bottles. Sixty-five of 300 (22%) bottles had no growth detected; 50 from the Bactec (5 aerobic and 45 anaerobic) and 15 from the BacT (all anaerobic). Terminal subculture of “negative” bottles demonstrated viable yeast growth from all 65 bottles, representing 65 false-negatives. The mean time to growth detection in the BacT system was 25.62 h while the Bactec was 27.30 h (P < 0.01). Both automated blood culture systems detected all episodes of simulated candidemia when specialized mycology media were used. However, when only standard aerobic and anaerobic media were used, the BacT performed better than the Bactec in overall growth detection, time to growth detection, and number of false-negatives.

Invasive mold infections following combat-related injuries.

BACKGROUND Major advances in combat casualty care have led to increased survival of patients with complex extremity trauma. Invasive fungal wound infections (IFIs) are an uncommon, but increasingly recognized, complication following trauma that require greater understanding of risk factors and clinical findings to reduce morbidity. METHODS The patient population includes US military personnel injured during combat from June 2009 through December 2010. Case definition required wound necrosis on successive debridements with IFI evidence by histopathology and/or microbiology (Candida spp excluded). Case finding and data collected through the Trauma Infectious Disease Outcomes Study utilized trauma registry, hospital records or operative reports, and pathologist review of histopathology specimens. RESULTS A total of 37 cases were identified: proven (angioinvasion, n=20), probable (nonvascular tissue invasion, n=4), and possible (positive fungal culture without histopathological evidence, n=13). In the last quarter surveyed, rates reached 3.5% of trauma admissions. Common findings include blast injury (100%) during foot patrol (92%) occurring in southern Afghanistan (94%) with lower extremity amputation (80%) and large volume blood transfusion (97.2%). Mold isolates were recovered in 83% of cases (order Mucorales, n=16; Aspergillus spp, n=16; Fusarium spp, n=9), commonly with multiple mold species among infected wounds (28%). Clinical outcomes included 3 related deaths (8.1%), frequent debridements (median, 11 cases), and amputation revisions (58%). CONCLUSIONS IFIs are an emerging trauma-related infection leading to significant morbidity. Early identification, using common characteristics of patient injury profile and tissue-based diagnosis, should be accompanied by aggressive surgical and antifungal therapy (liposomal amphotericin B and a broad-spectrum triazole pending mycology results) among patients with suspicious wounds.

Presumptive identification of Candida species other than C. albicans, C. krusei, and C. tropicalis with the chromogenic medium CHROMagar Candida.

BackgroundCHROMagar Candida (CaC) is increasingly being reported as a medium used to differentiate Candida albicans from non-albicans Candida (NAC) species. Rapid identification of NAC can assist the clinician in selecting appropriate antifungal therapy. CaC is a differential chromogenic medium designed to identify C. albicans, C. krusei, and C. tropicalis based on colony color and morphology. Some reports have proposed that CaC can also reliably identify C. dubliniensis and C. glabrata.MethodsWe evaluated the usefulness of CaC in the identification of C. dubliniensis, C. famata, C. firmetaria, C. glabrata, C. guilliermondii, C. inconspicua, C. kefyr, C. lipolytica, C. lusitaniae, C. norvegensis, C. parapsilosis, and C. rugosa.ResultsMost NAC produced colonies that were shades of pink, lavender, or ivory. Several isolates of C. firmetaria and all C. inconspicua produced colonies difficult to differentiate from C. krusei. Most C. rugosa isolates produced unique colonies with morphology like C. krusei except in a light blue-green color. C. glabrata isolates produced small dark violet colonies that could be differentiated from the pink and lavender colors produced by other species. All seventeen isolates of C. dubliniensis produced green colonies similar to those produced by C. albicans.ConclusionC. glabrata and C. rugosa appear distinguishable from other species using CaC. Some NAC, including C. firmetaria and C. inconspicua, could be confused with C. krusei using this medium.