The Impact of Standardized Infectious Diseases Consultation on Postsplenectomy Care and Outcomes.

Background: Patients who receive splenectomy are at risk for overwhelming postsplenectomy infection (OPSI). Guidelines recommend that adult asplenic patients receive a complement of vaccinations, education on the risks of OPSI, and on-demand antibiotics. However, prior literature suggests that a majority of patients who have had a splenectomy receive incomplete asplenic patient care and thus remain at increased risk. This study assessed the impact of standardized involvement of infectious diseases (ID) providers on asplenic patient care outcomes in patients undergoing splenectomy. Methods: A quasi-experimental study design compared a prospective cohort of patients undergoing splenectomy from August 2017 to June 2021 who received standardized ID involvement in care of the asplenic patient with a historic control cohort of patients undergoing splenectomy at the same institution from January 2010 through July 2017 who did not. There were 11 components of asplenic patient care defined as primary outcomes. Secondary outcomes included the occurrence of OPSI, death, and death from OPSI. Results: Fifty patients were included in the prospective intervention cohort and 128 in the historic control cohort. There were significant improvements in 9 of the 11 primary outcomes in the intervention arm as compared with the historic controls. Survival analysis showed no statistically significant difference in the incidence of OPSI-free survival between the groups (P = .056), though there was a trend toward improvement in the prospective intervention arm. Conclusions: Standardized involvement of an ID provider in the care of patients undergoing splenectomy improves asplenic patient care outcomes. Routine involvement of ID in this setting may be warranted.

Resistance patterns and clinical outcomes of Klebsiella pneumoniae and invasive Klebsiella variicola in trauma patients.

Recent reclassification of the Klebsiella genus to include Klebsiella variicola, and its association with bacteremia and mortality, has raised concerns. We examined Klebsiella spp. infections among battlefield trauma patients, including occurrence of invasive K. variicola disease. Klebsiella isolates collected from 51 wounded military personnel (2009-2014) through the Trauma Infectious Disease Outcomes Study were examined using polymerase chain reaction (PCR) and pulsed-field gel electrophoresis. K. variicola isolates were evaluated for hypermucoviscosity phenotype by the string test. Patients were severely injured, largely from blast injuries, and all received antibiotics prior to Klebsiella isolation. Multidrug-resistant Klebsiella isolates were identified in 23 (45%) patients; however, there were no significant differences when patients with and without multidrug-resistant Klebsiella were compared. A total of 237 isolates initially identified as K. pneumoniae were analyzed, with 141 clinical isolates associated with infections (remaining were colonizing isolates collected through surveillance groin swabs). Using PCR sequencing, 221 (93%) isolates were confirmed as K. pneumoniae, 10 (4%) were K. variicola, and 6 (3%) were K. quasipneumoniae. Five K. variicola isolates were associated with infections. Compared to K. pneumoniae, infecting K. variicola isolates were more likely to be from blood (4/5 versus 24/134, p = 0.04), and less likely to be multidrug-resistant (0/5 versus 99/134, p<0.01). No K. variicola isolates demonstrated the hypermucoviscosity phenotype. Although K. variicola isolates were frequently isolated from bloodstream infections, they were less likely to be multidrug-resistant. Further work is needed to facilitate diagnosis of K. variicola and clarify its clinical significance in larger prospective studies.

Case Report: Miltefosine Failure and Spontaneous Resolution of Cutaneous Leishmaniasis braziliensis.

Cutaneous leishmaniasis (CL) is often caused by Leishmania braziliensis (L. braziliensis) in South America. Because of the risk for mucocutaneous leishmaniasis, L. braziliensis is frequently treated with parenteral or oral medications. Here, we present a case of a young woman with L. braziliensis (CL) that did not respond to miltefosine but eventually experienced spontaneous resolution. This case highlights the potential for treatment failure and the importance of clinical monitoring in the setting of cutaneous leishmaniasis caused by L. braziliensis.

Opportunities and Obstacles in the Prevention of Skin and Soft-Tissue Infections Among Military Personnel.

INTRODUCTION: Skin and soft-tissue infections (SSTIs) are an important cause of infectious disease morbidity among military populations. Due to the high direct and indirect costs associated with SSTIs, particularly with methicillin-resistant Staphylococcus aureus (MRSA) infections, there remains a critical need for the development and evaluation of SSTI prevention strategies among high-risk military personnel. Herein, we review efforts of the Infectious Disease Clinical Research Program (IDCRP) related to the prevention of SSTIs in the military. METHODS: The IDCRP of the Uniformed Services University has conducted clinical research protocols on SSTI epidemiology and prevention among military personnel since 2009. Observational studies have examined the epidemiology of Staphylococcus aureus colonization and SSTI in training and deployment settings. Two randomized controlled trials of personal hygiene strategies for SSTI prevention at Marine Corps Base Quantico (Virginia) and Fort Benning (Georgia) were performed. Lastly, two vaccine trials have been conducted by the IDCRP, including a Phase 2 S. aureus vaccine trial (currently ongoing) among military trainees. RESULTS: Military recruits and deployed personnel experience an intense and prolonged exposure to S. aureus, the major causative agent of SSTI. The burden of S. aureus colonization and SSTI is particularly high in military trainees. Hygiene-based trials for S. aureus decolonization among military trainees were not effective in reducing rates of SSTI. In January 2018, the IDCRP initiated a Phase 2 S. aureus vaccine trial among the US Army Infantry training population at Fort Benning. CONCLUSIONS: In the military, a disproportionate burden of SSTIs is borne by the recruit population. Strategies relying upon routine application of agents for S. aureus decolonization have not been effective in preventing SSTIs. A novel S. aureus vaccine candidate is being currently evaluated in a military training population and may represent a new opportunity to prevent SSTIs for the military.

The US Military HIV Natural History Study: Informing Military HIV Care and Policy for Over 30 Years.

INTRODUCTION: In October 1985, 4 years after the initial descriptions of the acquired immunodeficiency syndrome (AIDS), the U.S. Department of Defense (DoD) began routine screening for human immunodeficiency virus (HIV) infection to prevent infected recruits from exposure to live virus vaccines, implemented routine active-duty force screening to ensure timely care and help protect the walking blood bank, and initiated the U.S. Military HIV Natural History Study (NHS) to develop epidemiologic, clinical, and basic science evidence to inform military HIV policy and establish a repository of data and specimens for future research. Here, we have reviewed accomplishments of the NHS over the past 30 years and sought to describe relevant trends among NHS subjects over this time, with emphasis on combination antiretroviral therapy (cART) use and non-AIDS comorbidities. METHODS: Subjects who were prospectively enrolled in the NHS from 1986 through 2015 were included in this analysis. Time periods were classified by decade of study conduct, 1986-1995, 1996-2005, and 2006-2015, which also correlate approximately with pre-, early-, and late-combination ART (cART) eras. Analyses included descriptive statistics and comparisons among decades. We also evaluated mean community log10 HIV viral load (CVL) and CD4 counts for each year. RESULTS: A total of 5,758 subjects were enrolled between 1986 and 2015, of whom 92% were male with a median age of 28 years, and 45% were African-American, 42% Caucasian, and 13% Hispanic/other. The proportion of African-Americans remained stable over the decades (45%, 47%, and 42%, respectively), while the proportion of Hispanic/other increased (10%, 13%, and 24%, respectively). The CD4 count at HIV diagnosis has remained high (median 496 cells/uL), while the occurrence of AIDS-defining conditions (excluding low CD4 count) has decreased by decade (36.7%, 5.4%, and 2.9%, respectively). Following the introduction of effective cART in 1996, CVL declined through 2000 as use increased and then plateaued until guidelines changed. After 2004, cART use again increased and CVL declined further until 2012-15 when the vast majority of subjects achieved viral suppression. Non-AIDS comorbidities have remained common, with approximately half of subjects experiencing one or more new diagnoses overall and nearly half of subjects diagnosed between 2006 and 2015, in spite of their relatively young age, shorter median follow-up, and wide use of cART. CONCLUSIONS: The US Military HIV NHS has been critical to understanding the impact of HIV infection among active-duty service members and military beneficiaries, as well as producing insights that are broadly relevant. In addition, the rich repository of NHS data and specimens serves as a resource to investigators in the DoD, NIH, and academic community, markedly increasing scientific yield and identifying novel associations. Looking forward, the NHS remains relevant to understanding host factor correlates of virologic and immunologic control, biologic pathways of HIV pathogenesis, causes and consequences of residual inflammation in spite of effective cART, identifying predictors of and potential approaches to mitigation of excess non-AIDS comorbidities, and helping to understand the latent reservoir.

Urinary Tract Infections after Combat-Related Genitourinary Trauma.

Background: We examined clinical outcomes among combat casualties with genitourinary injuries after blast trauma. Methods: Characteristics, clinical care, urologic complications, and infections for subjects enrolled in the Trauma Infectious Disease Outcomes Study (TIDOS) were collected from Department of Defense (DOD) and Department of Veterans Affairs (VA) sources. Logistic regression identified predictors for urinary tract infections (UTIs) after genitourinary trauma. Results: Among 530 TIDOS enrollees who entered VA care, 89 (17%) sustained genitourinary trauma. The majority of subjects (93%) were injured via a blast and 27% had a dismounted complex blast injury (DCBI). Sexual dysfunction was reported with 36% of subjects, whereas 14% had urinary retention/incontinence and 8% had urethral stricture. Urologic complications were comparable between patients with and without DCBIs. Nineteen (21%) subjects had one or more UTI with a total of 40 unique UTI events (25% during initial hospitalization and 75% during subsequent DOD or VA care). The UTI incidence rate was 0.89 per patient-year during initial hospitalization, 0.05 per patient-year during DOD follow-up, and 0.07 per patient-year during VA healthcare. Subjects with UTIs had a higher proportion of bladder injury (53% vs. 13%; p < 0.001), posterior urethral injury (26% vs. 1%; p = 0.001), pelvic fracture (47% vs. 4%; p < 0.001), soft-tissue infection of the pelvis/hip (37% vs. 4%; p = 0.001), urinary catheterization (47% vs. 11%; p < 0.001), urinary retention or incontinence (42% vs. 6%; p < 0.001), and stricture (26% vs. 3%; p = 0.004) compared with patients with genitourinary trauma and no UTI. Independent UTI risk factors were occurrence of a soft-tissue infection at the pelvis/hip, trauma to the urinary tract, and transtibial amputation. Conclusions: Among combat casualties with genitourinary trauma, UTIs are a common complication, particularly with severe blast injury and urologic sequelae. Episodes of UTIs typically occur early after the initial injury while in DOD care, however, recurrent infections may continue into long-term VA care.

Combat-Related Extremity Wounds: Injury Factors Predicting Early Onset Infections.

We examined risk factors for combat-related extremity wound infections (CEWI) among U.S. military patients injured in Iraq and Afghanistan (2009-2012). Patients with ≥1 combat-related, open extremity wound admitted to a participating U.S. hospital (≤7 days postinjury) were retrospectively assessed. The population was classified based upon most severe injury (amputation, open fracture without amputation, or open soft-tissue injury defined as non-fracture/non-amputation wounds). Among 1271 eligible patients, 395 (31%) patients had ≥1 amputation, 457 (36%) had open fractures, and 419 (33%) had open soft-tissue wounds as their most severe injury, respectively. Among patients with traumatic amputations, 100 (47%) developed a CEWI compared to 66 (14%) and 12 (3%) patients with open fractures and open soft-tissue wounds, respectively. In a Cox proportional hazard analysis restricted to CEWIs ≤30 days postinjury among the traumatic amputation and open fracture groups, sustaining an amputation (hazard ratio: 1.79; 95% confidence interval: 1.25-2.56), blood transfusion ≤24 hours postinjury, improvised explosive device blast, first documented shock index ≥0.80, and >4 injury sites were independently associated with CEWI risk. The presence of a non-extremity infection at least 4 days prior to a CEWI diagnosis was associated with lower CEWI risk, suggesting impact of recent exposure to directed antimicrobial therapy. Further assessment of early clinical management will help to elucidate risk factor contribution. The wound classification system provides a comprehensive approach in assessment of injury and clinical factors for the risk and outcomes of an extremity wound infection.

Microbiology of combat-related extremity wounds: Trauma Infectious Disease Outcomes Study.

We present extremity wound microbiology data from 250 combat casualties (2009-2012). Confirmed extremity wound infections (EWIs) were based on clinical and laboratory findings. Suspected EWIs had isolation of organisms from wound cultures with associated signs/symptoms not meeting clinical diagnostic criteria. Colonized wounds had organisms isolated without any infection suspicion. A total of 335 confirmed EWIs (131 monomicrobial and 204 polymicrobial) were assessed. Gram-negative bacteria were predominant (57% and 86% of monomicrobial and polymicrobial infections, respectively). In polymicrobial infections, 61% grew only bacteria, while 30% isolated bacteria and mold. Multidrug resistance was observed in 32% of isolates from first monomicrobial EWIs ±3 days of diagnosis, while it was 44% of isolates from polymicrobial EWIs. Approximately 96% and 52% of the suspected and colonized wounds, respectively, shared ≥1 organism in common with the confirmed EWI on the same patient. Understanding of combat-related EWIs can lead to improvements in combat casualty care.

Nosocomial outbreak of influenza A H3N2 in an inpatient oncology unit related to health care workers presenting to work while ill.

OBJECTIVE: To describe an outbreak of influenza A in an oncology unit, highlighting infection control methods implemented, and examining reasons health care workers (HCWs) present to work with influenza-like illness (ILI). METHODS: Confirmed cases were defined by the presence of ILI and a positive nasopharyngeal polymerase chain reaction swab for influenza A H3. Probable cases were defined as exposed HCWs with ILI who were unavailable for polymerase chain reaction testing. Infection prevention measures included closing the ward for new admissions, oseltamivir prophylaxis for all exposed groups, and dismissal from work of HCWs with ILI until resolution of symptoms. An anonymous survey of the cases in our HCWs was conducted to better elucidate reasons behind presenteeism. RESULTS: Over the course of 8 days (November 16, 2017, to November 22, 2017), influenza was diagnosed in 7 of 10 inpatients on the oncology ward, 16 HCWs (14 confirmed, 2 probable), and 2 visitors. The suspected index case was an HCW. Of the surveyed HCWs, 64% presented to work despite feeling ill (ie, presenteeism). The most common reason was "sense of duty as a health care worker." CONCLUSIONS: This nosocomial outbreak of influenza highlights the challenges of protecting inpatients from viral respiratory tract infections. HCWs and patient visitors with ILI should avoid work or visiting until resolution of peak respiratory symptoms and adhere to strict respiratory etiquette.

Factors Influencing Selection of Infectious Diseases Training for Military Internal Medicine Residents.

Background: Applications to infectious diseases fellowships have declined nationally; however, the military has not experienced this trend. In the past 6 years, 3 US military programs had 58 applicants for 52 positions. This study examines military resident perceptions to identify potential differences in factors influencing career choice, compared with published data from a nationwide cohort. Methods: An existing survey tool was adapted to include questions unique to the training and practice of military medicine. Program directors from 11 military internal medicine residencies were asked to distribute survey links to their graduating residents from December 2016 to January 2017. Data were categorized by ID interest. Result: The response rate was 51% (n = 68). Of respondents, 7% were ID applicants, 40% considered ID but reconsidered, and 53% were uninterested. Of those who considered ID, 73% changed their mind in their second and third postgraduate years and cited salary (22%), lack of procedures (18%), and training length (18%) as primary deterrents to choosing ID. Active learning styles were used more frequently by ID applicants to learn ID concepts than by those who considered or were uninterested in ID (P = .02). Conclusions: Despite differences in the context of training and practice among military trainees compared with civilian colleagues, residents cited similar factors affecting career choice. Interest in global health was higher in this cohort. Salary continues to be identified as a deterrent to choosing ID. Differences between military and civilian residents' desire to pursue ID fellowship are likely explained by additional unmeasured factors deserving further study.

Antimicrobial Prophylaxis with Combat-Related Open Soft-Tissue Injuries.

INTRODUCTION: All Department of Defense (DoD) guidance documents recommend cefazolin or clindamycin as post-trauma antibiotic prophylaxis for open soft-tissue injuries. Although not advocated, some patients with open soft-tissue injuries also received expanded Gram-negative coverage (EGN) prophylaxis based on the judgment of front-line trauma providers. During the study period, revised guidelines in 2011/2012 re-emphasized recommendations for using cefazolin or clindamycin, and stewardship efforts in the DoD trauma community aimed to reduce the practice of adding EGN to guideline-recommended antibiotic prophylaxis. Our objective was to examine antibiotic utilization among wounded military personnel with open extremity soft-tissue injuries over a 5-yr period and assess the impact on infectious outcomes in patients who received EGN prophylaxis versus guideline-directed prophylaxis. METHODS: The study population included military personnel with open extremity soft-tissue injuries sustained in Iraq and Afghanistan (2009-2014) who transferred to participating hospitals in the USA following medical evacuation. The analysis was restricted to patients who were hospitalized for at least seven days at a U.S. facility and excluded those who sustained open fractures. Post-trauma antibiotic prophylactic regimens were defined as narrow if they followed recommended guidance (e.g., IV cefazolin or clindamycin) or EGN coverage when the narrow regimen also included fluoroquinolones and/or aminoglycosides. Intravenous amoxicillin-clavulanate, which is commonly used at non-U.S. coalition theater hospitals, was also classified as narrow because it conformed to coalition antibiotic prophylaxis guidelines. This study was approved by the Infectious Disease Institutional Review Board of the Uniformed Services University of the Health Sciences. RESULTS: A total of 287 wounded personnel with open soft-tissue injuries were assessed, of which 212 (74%) received narrow prophylaxis and 75 (26%) received EGN coverage (p < 0.001). Among patients in the narrow prophylaxis group, 81% were given cefazolin and/or clindamycin, while 19% received amoxicillin-clavulanate. In the EGN group, 88% and 12% received a fluoroquinolone and aminoglycoside, respectively. Use of EGN coverage significantly declined during the study period from 39% in 2009-2010 to 11% in 2013-2014 (p < 0.001). Approximately 3% of patients who received a narrow regimen developed an extremity skin and soft-tissue infection, while there were no skin and soft-tissue infections among patients in the EGN coverage group. Nonetheless, this was not a significant difference (p = 0.345). In addition, the proportion of non-extremity infections was not significantly different between narrow and EGN regimen groups (11% and 15%, respectively). There were also no significant differences between the narrow and EGN regimen groups related to duration of hospitalization (median of 19 versus 20 d). CONCLUSION: Use of non-guideline directed EGN-based post-trauma antibiotic prophylaxis does not improve infectious outcomes nor does it shorten hospital stay.

Military Internal Medicine Resident Decision to Apply to Fellowship and Extend Military Commitment.

Introduction: Nationally, the number of internal medicine physicians practicing in primary care has decreased amidst increasing interest in hospitalist medicine. Current priorities in the Military Health System include access to primary care and retention of trained personnel. Recently, we have conducted a study of military internal medicine residents' decision to enter infectious disease. As part of our larger effort, we saw an opportunity to characterize factors impacting decision making of internal medicine residents' desire to apply for subspecialty training and to extend active duty service obligations. Materials and Methods: Questions were developed after discussion with various military graduate medical education and internal medicine leaders, underwent external review, and were added to a larger question set. The survey link was distributed electronically to all U.S. military affiliated residencies' graduating internal medicine residents in December 2016-January 2017. Data were analyzed by decision to apply to fellowship and decision to extend military obligation using Fisher's exact test or Pearon's chi-square test. Results: Sixty-eight residents from 10 of 11 military residency programs responded, for a response rate of 51%. The majority (62%) applied to fellowship to start after residency completion. Reasons cited for applying to fellowship included wanting to become a specialist as soon as possible (74%), wishing to avoid being a general internist (57%), and because they are unable to practice as a hospitalist in the military (52%). Fellowship applicants were more likely to plan to extend their military obligation than non-applicants, as did those with longer duration of military commitments. No other factors, including Uniformed Services University attendance or participation in undergraduate military experiences, were found to impact plan to extend active duty service commitment. Conclusion: The majority of graduating internal medicine residents apply for fellowship and report a desire to avoid being a general internist. Prospective fellows anticipate extending their active duty commitment, as do those with longer commitments.

Multi-Drug-Resistant Gram-Negative Infections in Deployment-Related Trauma Patients.

BACKGROUND: The contribution of multi-drug-resistant gram-negative bacilli infections (MDRGN-I) in patients with trauma is not well described. We present characteristics of MDRGN-Is among military personnel with deployment-related trauma (2009-2014). PATIENTS AND METHODS: Data from the Trauma Infectious Disease Outcomes Study were assessed for infectious outcomes and microbial recovery. Infections were classified using standardized definitions. Gram-negative bacilli were defined as multi-drug-resistant if they showed resistance to ≥3 antibiotic classes or were producers of extended-spectrum ß-lactamase or carbapenemases. RESULTS: Among 2,699 patients admitted to participating U.S. hospitals, 913 (33.8%) experienced ≥1 infection event, of which 245 (26.8%) had a MDRGN-I. There were 543 MDRGN-I events (24.6% of unique 2,210 infections) with Escherichia coli (48.3%), Acinetobacter spp. (38.6%), and Klebsiella pneumoniae (8.4%) as the most common MDRGN isolates. Incidence of MDRGN-I was 9.1% (95% confidence interval [CI]: 8.0-10.2). Median time to MDRGN-I event was seven days with 75% occurring within 13 days post-trauma. Patients with MDRGN-Is had a greater proportion of blast injuries (84.1% vs. 62.5%; p < 0.0001), traumatic amputations (57.5% vs. 16.3%; p < 0.0001), and higher injury severity (82.0% had injury severity score ≥25 vs. 33.7%; p < 0.0001) compared with patients with either no infections or non-MDRGN-Is. Furthermore, MDRGN-I patients were more frequently admitted to the intensive care unit (90.5% vs. 48.5%; p < 0.0001), colonized with a MDRGN before infection (58.0% vs. 14.7%; p < 0.0001), and required mechanical ventilation (78.0% vs. 28.8% p < 0.0001). Antibiotic exposure before the MDRGN-I event was significantly higher across antibiotic classes except first generation cephalosporins and tetracyclines, which were very commonly used with all patients. Regarding outcomes, patients with MDRGN-Is had a longer length of hospitalization than the comparator group (53 vs. 18 days; p < 0.0001). CONCLUSIONS: We found a high rate of MDRGN-I in our population characterized by longer hospitalization and greater injury severity. These findings inform treatment and infection control decisions in the trauma patient population.

Guidelines for the prevention of travel-associated illness in older adults.

International travel to the developing world is becoming more common in elderly patients (defined here as individuals greater than 65 years old). When providing pre-travel counseling, providers must appreciate the changing physiology, comorbidities, immunity and pharmacokinetics associated with the aging process to prepare elderly patients for the stressors of international travel. These guidelines present an evidence-based approach to pre-travel counseling, immunization, and pharmacology concerns unique to elderly patients seeking care in a travel clinic setting.

Early infectious outcomes after addition of fluoroquinolone or aminoglycoside to posttrauma antibiotic prophylaxis in combat-related open fracture injuries.

BACKGROUND: We examined combat-related open extremity fracture infections as a function of whether posttrauma antimicrobial prophylaxis included expanded Gram-negative (EGN) coverage. METHODS: Military personnel with open extremity fractures sustained in Iraq and Afghanistan (2009-2014) who transferred to participating hospitals in the United States were assessed. The analysis was restricted to patients with a U.S. hospitalization period of ≥7 days. Prophylaxis was classified as narrow (e.g., IV cefazolin, clindamycin, and/or amoxicillin-clavulanate) or EGN, if the prophylactic regimen included fluoroquinolones and/or aminoglycosides. RESULTS: The study population included 1,044 patients, of which 585 (56%) and 459 (44%) received narrow and EGN coverage, respectively (p < 0.001). Skin and soft-tissue infections (SSTIs) were more common among patients who received narrow prophylaxis compared to EGN coverage (28% vs. 22%; p = 0.029), whereas osteomyelitis rates were comparable between regimens (8%). Similar findings were noted when endpoints were measured at 2 and 4 weeks postinjury. There was no significant difference related to length of hospitalization between narrow and EGN regimens (median: 34 and 32 days, respectively) or operating room visits (median: 5 and 4). A higher proportion of EGN coverage patients had Gram-negative organisms isolated that were not susceptible to fluoroquinolones and/or aminoglycosides (49% vs. 40%; p < 0.001). In a Cox proportional model, narrow prophylaxis was independently associated with an increased risk of extremity SSTIs (hazard ratio: 1.41; 95% confidence interval: 1.09-1.83). DISCUSSION: Despite seeing a small benefit with EGN coverage related to a reduction of SSTIs, it does not decrease the risk of osteomyelitis, and there seems to be a cost of increased antibiotic resistance associated with use. Overall, our findings support the current post-combat trauma antibiotic prophylaxis guidelines, which recommend the use of cefazolin or clindamycin with open fractures. LEVEL OF EVIDENCE: Prognostic/Epidemiological, Level II; Therapy, level IV.

Brief Report: Prevalence of Posttreatment Controller Phenotype Is Rare in HIV-Infected Persons After Stopping Antiretroviral Therapy.

BACKGROUND: Posttreatment control of HIV infection is a rare phenomenon primarily described among those initiating treatment with antiretroviral therapy (ART) during early/acute HIV infection. METHODS: We examined a large, well-characterized cohort of HIV-infected Department of Defense beneficiaries for the presence of posttreatment controllers (PTCs) whom we defined as individuals with sustained viral suppression for ≥6 months after discontinuation of ART. We defined those who became viremic within 6 months of discontinuing ART as rapid viremics (RVs) and compared demographic and clinical characteristics, CD4 counts, and viral loads prior, during, and after ART discontinuation between the 2 groups. RESULTS: From a cohort of 6070 patients, we identified 95 who had been treated with ART for 2 years or more who subsequently discontinued ART and had viral load assessments available after discontinuation. Four (4.2%) of these 95 met our definition of PTC. The duration of viral suppression off of ART ranged from 267 to 1058 days with 1 of the 4 restarting ART without having redeveloped a significant viremia. All 4 patients initiated ART during chronic HIV infection. Demographic and clinical characteristics of PTCs were similar to RVs. CONCLUSIONS: While posttreatment control has predominantly been described among individuals who initiated ART in early/acute HIV infection, we identified 4 PTCs who started ART during chronic infection suggesting that posttreatment control also occurs among such patients. The rarity of PTCs identified in our cohort is consistent with reports from previous studies.

Analysis of Serial Isolates of mcr-1-Positive Escherichia coli Reveals a Highly Active ISApl1 Transposon.

The emergence of a transferable colistin resistance gene (mcr-1) is of global concern. The insertion sequence ISApl1 is a key component in the mobilization of this gene, but its role remains poorly understood. Six Escherichia coli isolates were cultured from the same patient over the course of 1 month in Germany and the United States after a brief hospitalization in Bahrain for an unconnected illness. Four carried mcr-1 as determined by real-time PCR, but two were negative. Two additional mcr-1-negative E. coli isolates were collected during follow-up surveillance 9 months later. All isolates were analyzed by whole-genome sequencing (WGS). WGS revealed that the six initial isolates were composed of two distinct strains: an initial ST-617 E. coli strain harboring mcr-1 and a second, unrelated, mcr-1-negative ST-32 E. coli strain that emerged 2 weeks after hospitalization. Follow-up swabs taken 9 months later were negative for the ST-617 strain, but the mcr-1-negative ST-32 strain was still present. mcr-1 was associated with a single copy of ISApl1, located on a 64.5-kb IncI2 plasmid that shared >95% homology with other mcr-1 IncI2 plasmids. ISApl1 copy numbers ranged from 2 for the first isolate to 6 for the final isolate, but ISApl1 movement was independent of mcr-1 Some movement was accompanied by gene disruption, including the loss of genes encoding proteins involved in stress responses, arginine catabolism, and l-arabinose utilization. These data represent the first comprehensive analysis of ISApl1 movement in serial clinical isolates and reveal that, under certain conditions, ISApl1 is a highly active IS element whose movement may be detrimental to the host cell.