Practice Patterns of Infectious Diseases Physicians in Transitioning From Intravenous to Oral Therapy in Patients With Bacteremia.

BACKGROUND: Bacteremia in adult patients has traditionally been treated with extended courses of intravenous antibiotics. Data on the use of (or rapid transition to) oral therapy are limited. METHODS: Adult infectious disease physicians participating in the Infectious Diseases Society of America Emerging Infections Network (EIN) were surveyed regarding their use of oral antibiotics in patients with bacteremia. Respondents were asked to assume that patients were hemodynamically stable, recovered bacteria were susceptible to potential antibiotics, adequate source control had been achieved, and patients had adequate gastrointestinal absorption. Variables of specific bacteria, oral agent, and associated infection were included. RESULTS: A total of 655 (50%) of 1321 EIN participants responded. Under certain conditions, 88% would transition patients with Gram-negative bacteremia to complete a course of therapy with oral antibiotics; 71% would transition patients with Gram-positive bacteremia to oral agents. Only 78 (12%) respondents would not treat any bacteremic patient with oral agents. Most respondents (≥75%) were comfortable treating infections secondary to Enterobacteriaceae, Salmonella, Pseudomonas, Stenotrophomonas, Streptococcus pneumoniae, and ß-hemolytic streptococci with oral agents. Fewer than 20% endorsed use of oral antibiotics for Staphylococcus aureus or in cases of endocarditis. Fluoroquinolones and trimethoprim-sulfamethoxazole were the preferred agents in Gram-negative bacteremia; linezolid and ß-lactams were the preferred agents in Gram-positive bacteremia. CONCLUSIONS: In select circumstances, the majority of respondents would transition patients to oral antibiotics, in both Gram-negative and Gram-positive bacteremia. Most agreed with the use of oral agents in Gram-negative bacteremia caused by Enterobacteriaceae, but they would not use oral agents for Gram-positive bacteremia caused by S aureus or in endocarditis.

Necrotizing Mucormycosis of Wounds Following Combat Injuries, Natural Disasters, Burns, and Other Trauma.

Necrotizing mucormycosis is a devastating complication of wounds incurred in the setting of military (combat) injuries, natural disasters, burns, or other civilian trauma. Apophysomyces species, Saksenaea species and Lichtheimia (formerly Absidia) species, although uncommon as causes of sinopulmonary mucormycosis, are relatively frequent agents of trauma-related mucormycosis. The pathogenesis of these infections likely involves a complex interaction among organism, impaired innate host defenses, and biofilms related to traumatically implanted foreign materials. Effective management depends upon timely diagnosis, thorough surgical debridement, and early initiation of antifungal therapy.

Safety and immunogenicity of a recombinant Staphylococcus aureus α-toxoid and a recombinant Panton-Valentine leukocidin subunit, in healthy adults.

We conducted a randomized, double-blind, placebo-controlled dose-escalation study in healthy adults to evaluate the safety and immunogenicity of recombinant Staphylococcus aureus candidate vaccine antigens, recombinant α-toxoid (rAT) and a sub-unit of Panton-Valentine leukocidin (rLukS-PV). 176 subjects were enrolled and randomized within 1 of 11 treatment cohorts: monovalent rAT or rLukS-PV dosages of 10, 25, 50, and 100 µg; bivalent rAT:rLukS dosages of 10:10, 25:25, and 50:50 µg; and alum or saline placebo. All subjects were assessed at Days 0, 7, 14, 28, and 84. Subjects in the 50:50 µg bivalent cohort received a second injection on Day 84 and were assessed on Days 98 and 112. Incidence and severity of reactogenicity and adverse events (AEs) were compared. Geometric mean serum concentrations (GMC) and neutralizing activity of anti-rAT and anti-rLukS-PV IgG were assessed. Reactogenicity incidence was significantly higher in vaccine than placebo recipients (77% versus 55%, respectively; p = 0.006). However, 77% of reactogenicity events were mild and 19% were moderate in severity. The AE incidence and severity were similar between the cohorts. All monovalent and bivalent rAT dosages resulted in a significant increase in the anti-rAT IgG and anti- rLukS-PV GMCs between day 0 and 28 compared with placebo, and persisted through Day 84. Exploratory subgroup analyses suggested a higher GMC and neutralizing antibody titers for the 50 µg monovalent or bivalent rAT and rLukS-PV dose as compared to the other doses. No booster effect was observed after administration of the second dose. We conclude that the rAT and rLukS-PV vaccine formulations were well-tolerated and had a favorable immunogenicity profile, producing antibody with neutralizing activity through day 84. There was no benefit observed with a booster dose of the vaccine.

Changing Susceptibility of Staphylococcus aureus in a US Pediatric Population.

BACKGROUND: Staphylococcus aureus is a major cause of infection in both adult and pediatric populations. After several decades of increasing prevalence, the proportion of S aureus infections due to methicillin-resistant S aureus has been reported to be in decline in adults. Data for similar changes in pediatric populations are limited. METHODS: Evaluation of S aureus susceptibility data for pediatric patients receiving care in the US Military Health System was performed. Microbiology and demographic data were collected for years 2005 through 2014. Trends in antibiotic susceptibility results were evaluated. Clinical and demographic characteristics were explored to assess for association with antibiotic susceptibilities. RESULTS: In this study, 41 745 S aureus isolates from 39 207 pediatric patients were included. An overall increase in susceptibility of isolates to oxacillin was noted over this 10-year period; with over 60% of isolates oxacillin-susceptible in 2014. S aureus susceptibility to clindamycin declined over the study period; notably methicillin-susceptible S aureus susceptibility to clindamycin declined from 90% to 83% (P < .0001). Differences in oxacillin susceptibility between US regions decreased over time. CONCLUSIONS: Similar to recent trends seen in adults, the proportion of pediatric S aureus infections secondary to methicillin-resistant S aureus appear to be decreasing, as is variability in US geographical resistance rates. Increasing clindamycin resistance among methicillin-susceptible S aureus should raise caution in the use of empirical clindamycin in presumed S aureus infection. Clinicians should be aware of regional susceptibility patterns when choosing empirical regimens.

Interlaboratory agreement of pulsed-field gel electrophoresis identification of Leptospira serovars.

Leptospirosis may be caused by > 250 Leptospira serovars. Serovar classification is a complex task that most laboratories cannot perform. We assessed the interlaboratory reproducibility of a pulsed-field gel electrophoresis (PFGE) identification technique developed by the Centers for Disease Control and Prevention (CDC). Blinded exchange of 93 Leptospiraceae strains occurred between San Antonio Military Medical Center (SAMMC) and the CDC. PFGE was performed and gel images were analyzed and compared with patterns present in each laboratory's database (CDC database: > 800 strain patterns; SAMMC database: > 300 strain patterns). Overall, 93.7% (74 of 79) of strains present in each receiving laboratory's database were correctly identified. Five isolates were misidentified, and two isolates did not match serovar PFGE patterns in the receiving laboratory's database. Patterns for these seven isolates were identical between laboratories; four serovars represented misidentified reference strains. The PFGE methodology studied showed excellent interlaboratory reproducibility, enabling standardization and data sharing between laboratories.

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.

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.

Chlorhexidine gluconate reduces transmission of methicillin-resistant Staphylococcus aureus USA300 among Marine recruits.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) pulsed-field type (PFT) USA300 causes skin and soft tissue infections in military recruits and invasive disease in hospitals. Chlorhexidine gluconate (CHG) is used to reduce MRSA colonization and infection. The impact of CHG on the molecular epidemiology of MRSA is not known. OBJECTIVE: To evaluate the impact of 2% CHG-impregnated cloths on the molecular epidemiology of MRSA colonization. DESIGN: Cluster-randomized, double-blind, controlled trial. SETTING: Marine Officer Candidate School, Quantico, Virginia, in 2007. PARTICIPANTS: Military recruits. INTERVENTION: Thrice-weekly application of CHG-impregnated or control (Comfort Bath; Sage) cloths over the entire body. MEASUREMENTS: Baseline and serial (every 2 weeks) nasal and/or axillary swab samples were assessed for MRSA colonization. Molecular analysis was performed with pulsed-field gel electrophoresis. RESULTS: During training, 77 subjects (4.9%) acquired MRSA, 26 (3.3%) in the CHG group and 51 (6.5%) in the control group (P=.004). When analyzed for PFT, 24 subjects (3.1%) in the control group but only 6 subjects (0.8%) in the CHG group (P=.001) had USA300. Of the 167 colonizing isolates recovered from 77 subjects, 99 were recovered from the control group, including USA300 (40.4%), USA800 (38.4%), USA1000 (12.1%), and USA100 (6.1%), and 68 were recovered from the CHG group, including USA800 (51.5%), USA100 (23.5%), and USA300 (13.2%). CONCLUSIONS: CHG decreased the transmission of MRSA--more specifically, USA300--among military recruits. In addition, USA300 and USA800 outcompeted other MRSA PFTs at incident colonization. Future studies should evaluate the broad-based use of CHG to decrease transmission of USA300 in hospital settings.

Invasive fungal infections following combat-related injury.

Invasive mold infections are a rare complication of traumatic wounds. We examined the incidence and outcomes of these infections in combat wounds. A retrospective chart review from March 2002 through July 2008 of U.S. soldiers returning from Iraq and Afghanistan with traumatic wounds was performed. A confirmed fungal wound infection was defined as growth of a known pathogenic mold and visualization of fungal elements on histopathology. Six cases were identified for an incidence of 0.4 cases/1,000 admissions. The incidence of invasive mold infections increased over time (p = 0.008) with a peak of 5.2 cases/1,000 admissions in 2007. Isolated molds included Aspergillus (n = 4), Bipolaris (n = 2), and 1 each Mucor and Absidia. All patients were male with a mean age of 22. Blast (n = 5) and gunshot wound (n = 1) were the sources of injury. All patients had fever (mean 39.4 degrees C) and leukocytosis (mean white blood cell count 25 x 10(3)/microL). The average acute physiology and chronic health evaluation II score was 22. All patients received antifungal agents, surgical debridement, and 3 required amputation revision. Average length of stay was 97 days. There were no deaths. Invasive mold infections are a rare complication of combat wounds but are associated with significant morbidity and may be increasing in frequency.

Invasive Apophysomyces variabilis infection in a burn patient.

Apophysomyces variabilis is an emerging fungal pathogen that can cause significant infections in immunocompetent patients. We report a case of A. variabilis invasive wound infection in a 21-year-old male after a self-inflicted burn injury.

Correlation of American Burn Association sepsis criteria with the presence of bacteremia in burned patients admitted to the intensive care unit.

Severe burn injury is accompanied by a systemic inflammatory response, making traditional indicators of sepsis both insensitive and nonspecific. To address this, the American Burn Association (ABA) published diagnostic criteria in 2007 to standardize the definition of sepsis in these patients. These criteria include temperature (>39°C or <36°C), progressive tachycardia (>110 beats per minute), progressive tachypnea (>25 breaths per minute not ventilated or minute ventilation >12 L/minute ventilated), thrombocytopenia (<100,000/µl; not applied until 3 days after initial resuscitation), hyperglycemia (untreated plasma glucose >200 mg/dl, >7 units of insulin/hr intravenous drip, or >25% increase in insulin requirements over 24 hours), and feed intolerance >24 hours (abdominal distension, residuals two times the feeding rate, or diarrhea >2500 ml/day). Meeting >3 of these criteria should "trigger" concern for infection. In this initial assessment of the ABA sepsis criteria correlation with infection, the authors evaluated the ABA sepsis criteria's correlation with bacteremia because bacteremia is not associated with inherent issues of diagnosis as occurs with pneumonia or soft tissue infections, and blood cultures are typically obtained due to concern for ongoing infections falling within the definition of "septic." A retrospective electronic records review was performed to evaluate episodes of bacteremia in the United States Army Institute of Research from 2006 through 2007. A total of 196 patients were admitted during the study period who met inclusion criteria. The first positive and negative cultures, if present, from each patient were evaluated. This totaled 101 positive and 181 negative cultures. Temperature, heart rate, insulin resistance, and feed intolerance criteria were significant on univariate analysis. Only heart rate and temperature were found to significantly correlate with bacteremia on multivariate analysis. The receiver operating characteristic curve area for meeting >3 ABA sepsis criteria is 0.638 (95% confidence interval 0.573-0.704; P < .001). Among severe burn patients, the ABA trigger for sepsis did not correlate strongly with bacteremia in this retrospective chart review.

Longitudinal characterization of Acinetobacter baumannii-calcoaceticus complex, Klebsiella pneumoniae, and methicillin-resistant Staphylococcus aureus colonizing and infecting combat casualties.

Drug-resistant Acinetobacter baumannii-calcoaceticus complex, Klebsiella pneumoniae, and methicillin-resistant Staphylococcus aureus colonize and infect combat casualties from Iraq and Afghanistan. We retrospectively evaluated relatedness, by pulsed-field gel electrophoresis and antibiotic susceptibility testing, of isolates colonizing and infecting casualties over 2 years. Colonizing organisms were unrelated to isolates producing later infection in up to 27% of cases; most isolates underwent change in antibiotic susceptibilities. The same is true for serial infecting isolates recovered during hospitalization.

In vitro and in vivo activity of first generation cephalosporins against Leptospira.

Third generation cephalosporins are commonly used in the treatment of leptospirosis. The efficacy of first generation cephalosporins has been less well-studied. Susceptibility testing of 13 Leptospira strains (11 serovars) to cefazolin and cephalexin was conducted using broth microdilution. Median minimal inhibitory concentration (MIC) for cefazolin and cephalexin ranged from < 0.016 to 2 µg/mL (MIC(90) = 0.5 µg/mL) and from 1 to 8 µg/mL (MIC(90) = 8 µg/mL), respectively. Efficacy of cefazolin and cephalexin in an acute lethal hamster model of leptospirosis was studied. Survival rates for cefazolin were 80%, 100%, and 100%, and survival rates for cephalexin were 50%, 80%, and 100% (treated with 5, 25, and 50 mg/kg per day for 5 days, respectively). Each treatment group showed improved survival compared with no treatment (P < 0.01), and none of the therapies, regardless of dose, was statistically significantly different than doxycycline. These results support a potential role for first generation cephalosporins as alternative therapies for leptospirosis.

Efficacy of minocycline and tigecycline in a hamster model of leptospirosis.

Leptospirosis is a widespread zoonotic infection characterized by acute febrile illness. Severely ill patients may require empiric treatment with broad-spectrum antibiotics prior to definitive diagnosis. We evaluated the efficacy of minocycline and tigecycline against leptospirosis in a hamster model. Hamsters were treated with either minocycline (5, 10, or 25 mg/kg per day) or tigecycline (5, 10, or 25 mg/kg per day) for 5 days. Controls included untreated animals and doxycycline-treated animals (5 mg/kg per day). Nine days after infection, all untreated animals were dead. All treated hamsters survived to the end of study (day 21). Study groups showed significantly improved survival compared to the untreated group (P < .01). Minocycline and tigecycline showed survival benefit comparable to the standard treatment, doxycycline. In the absence of doxycycline, minocycline may be considered as an alternative, while tigecycline may be useful in the management of severely ill patients prior to a definitive diagnosis.

Association of methicillin-resistant Staphylococcus aureus (MRSA) colonization with high-risk sexual behaviors in persons infected with human immunodeficiency virus (HIV).

Methicillin-resistant Staphylococcus aureus (MRSA) infections are an important cause of morbidity, especially among human immunodeficiency virus (HIV)-infected persons. Since an increasing number of MRSA skin and soft tissue infections involve the perigenital areas, some have suggested that these infections may be sexually transmitted. We performed a cross-sectional study among HIV-infected adults from 4 geographically diverse United States military HIV clinics to determine the prevalence of and the factors (including sexual practices) associated with MRSA colonization. Swabs were collected from the nares, throat, axillae, groin area, and perirectal area for S. aureus colonization. Data on sociodemographic characteristics, medical conditions, and sexual history were collected. Multivariate logistic regression models evaluated factors associated with carriage. We studied 550 HIV-infected adults with a median age of 42 years; 93% were male; and race/ethnicity was white for 46%, African American for 35%, and other for 19%. Median CD4 count was 529 cells/mm, 11% had a history of a MRSA infection, and 21% had a sexually transmitted infection within the last year, including 8% with syphilis. One hundred eighty (33%) were colonized with S. aureus and 22 (4%) with MRSA. The most common location for carriage was the nares, followed by the perigenital area (groin or perirectal area). Factors associated with MRSA carriage in the multivariate analyses included a sexually transmitted infection in the last year (odds ratio [OR], 4.2; p<0.01), history of MRSA infection (OR, 9.4; p<0.01), and African American compared with white race/ethnicity (OR, 3.5; p=0.01). In separate multivariate models, syphilis, nongonococcal urethritis, and public bath use were also associated with MRSA carriage (all p<0.01). In conclusion, a history of recent sexually transmitted infections, including syphilis and urethritis, was associated with MRSA carriage. These data suggest that high-risk sexual activities may play a role in MRSA transmission.

Saksenaea erythrospora infection following combat trauma.

Saksenaea erythrospora is a newly described species of the order Mucorales which has not previously been reported as a cause of human infection. We report a fatal case of S. erythrospora invasive burn wound infection in a 26-year-old male injured during combat operations in Iraq.

Pythium aphanidermatum infection following combat trauma.

Pythium aphanidermatum is a fungus-like plant pathogen which has never been reported as a cause of human infection. We report a case of P. aphanidermatum invasive wound infection in a 21-year-old male injured during combat operations in Afghanistan.

Carbapenem susceptibility testing errors using three automated systems, disk diffusion, Etest, and broth microdilution and carbapenem resistance genes in isolates of Acinetobacter baumannii-calcoaceticus complex.

The Acinetobacter baumannii-calcoaceticus complex (ABC) is associated with increasing carbapenem resistance, necessitating accurate resistance testing to maximize therapeutic options. We determined the accuracy of carbapenem antimicrobial susceptibility tests for ABC isolates and surveyed them for genetic determinants of carbapenem resistance. A total of 107 single-patient ABC isolates from blood and wound infections from 2006 to 2008 were evaluated. MICs of imipenem, meropenem, and doripenem determined by broth microdilution (BMD) were compared to results obtained by disk diffusion, Etest, and automated methods (the MicroScan, Phoenix, and Vitek 2 systems). Discordant results were categorized as very major errors (VME), major errors (ME), and minor errors (mE). DNA sequences encoding OXA beta-lactamase enzymes (bla(OXA-23-like), bla(OXA-24-like), bla(OXA-58-like), and bla(OXA-51-like)) and metallo-ß-lactamases (MBLs) (IMP, VIM, and SIM1) were identified by PCR, as was the KPC2 carbapenemase gene. Imipenem was more active than meropenem and doripenem. The percentage of susceptibility was 37.4% for imipenem, 35.5% for meropenem, and 3.7% for doripenem. Manual methods were more accurate than automated methods. bla(OXA-23-like) and bla(OXA-24-like) were the primary resistance genes found. bla(OXA-58-like), MBLs, and KPC2 were not present. Both automated testing and manual testing for susceptibility to doripenem were very inaccurate, with VME rates ranging between 2.8 and 30.8%. International variability in carbapenem breakpoints and the absence of CLSI breakpoints for doripenem present a challenge in susceptibility testing.