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Technical Documents and References

Antimicrobial Resistance


Lesho, E., Chukwuma, U., Sparks, M., Neumann, C., Richesson, D., Clifford, R., Gierhart S. Waterman P. Hinkle, M. (2016, June). Anatomic, Geographic, and Taxon-Specific Relative Risks of Carbapenem Resistance in the Health Care System of the U.S. Department of Defense. Journal of Clinical Microbiology, 54(6), 1546-1551.

Anatomic, Geographic, and Taxon-Specific Relative Risks of Carbapenem Resistance in the Health Care System of the U.S. Department of Defense

Abstract: Carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter spp., and Enterobacteriaceae pose urgent public health threats. The differential burden, relative risks, associations with antimicrobial consumption, and temporal trends of those taxa in large, geographically diverse U.S. health systems remain under reported. Electronic records of all patients in a geographically dispersed 280-hospital managed-care system from 2005 to 2014 were reviewed. Carbapenem-resistant strains were identified based on Clinical and Laboratory Standards Institute guidelines and breakpoints. A total of 360,000 potentially carbapenem-resistant strains were identified from 14.7 million cultures (80% infecting and 20% surveillance). Isolation of bacteria overseas or isolation from the bloodstream was associated with a higher relative risks of carbapenem resistance (CR; P<0.0001). Enterobacteriaceae were isolated 11 times more frequently than P. aeruginosa and Acinetobacter spp. However, compared to Enterobacteriaceae, the CR levels were 73-fold and 210-fold higher in P. aeruginosa and Acinetobacter spp., respectively. Significant differences in the relative risk of CR between taxa, anatomic, and geographic locations persisted after adjustment for other variables, the biggest differences occurring between taxa. Overall, CR rates increased for Enterobacteriaceae (P_0.03) and decreased for Acinetobacter spp. and P. aeruginosa (P<0.0001). These data provide a useful baseline for resistance trending and have implications for surveillance. Infections acquired overseas and bloodstream infections are particularly important areas for continued monitoring.


Spencer, J. R., Milburn, E. K., & Chukwuma, U. (2016, March). Correlation Between Antimicrobial Resistance in Escherichia coli Infections in Hospitalized Patients and Rates of Inpatient Prescriptions for Selected Antimicrobial Agents, Department of Defense Hospitals, 2010–2014. Medical Surveillance Monthly Report, 23(3), 6-10.

Correlation Between Antimicrobial Resistance coli in Escherichia Infections in Hospitalized Patients and Rates of Inpatient Prescriptions for Selected Antimicrobial Agents

Abstract: During the past decade, increasing prevalence of antimicrobial resistance in Escherichia coli has complicated treatment of infections. Several studies have shown significant correlations between levels of susceptibility and levels of prescription use for preferred antimicrobials; however, most of these studies were conducted outside the U.S. and are outdated. This analysis aimed to identify inpatient E. coli infection trends and correlations between prescriptions and antimicrobial resistance observed among hospitalized Department of Defense beneficiaries during 2010–2014. A descending trend was observed for E. coli infection incidence during 2010–2013, with an upward trend noted during the last year of the study. Despite quarterly fluctuations, descending trends were noted among prescription rates and stable trends were observed for resistance rates throughout the study period. A statistically significant moderate and positive correlation (r=0.53; p=0.01) was noted between levels of ciprofloxacin prescriptions and ciprofloxacin resistance for E. coli isolates. Stewardship programs are encouraged to monitor this relationship.


Sutter, D. E., Milburn, E., Chukwuma, U., Dzialowy, N., Maranich, A. M., & Hospenthal, D. R. (2016). Changing Susceptibility of Staphylococcus aureus in a US Pediatric Population. Pediatrics, 137(3). e20153099

Changing Susceptibility of Staphylococcus aureus in a US Pediatric Population

Abstract: 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. 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. 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. 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.


Lesho, E. P., Waterman, P. E., Chukwuma, U., McAuliffe, K., Neumann, C., Julius, M. D., . . . Kester, K. E. (2014). The Antimicrobial Resistance Monitoring and Research (ARMoR) Program: the Department of Defense's Response to Escalating Antimicrobial Resistance. Oxford University Press on behalf of the Infectious Diseases Society of America 2014.

The Antimicrobial Resistance Monitoring and Research (ARMoR) Program: the Department of Defense's Response to Escalating Antimicrobial Resistance

Abstract: Responding to escalating antimicrobial resistance (AMR), the US Department of Defense implemented an enterprise-wide collaboration termed the Antimicrobial Resistance Monitoring and Research Program to aid in infection prevention and control. It consists of a network of epidemiologists, bioinformaticists, microbiology researchers, policy-makers, hospital-based infection preventionists, and healthcare providers who collaborate to collect relevant AMR data, conduct centralized molecular characterization, and use AMR characterization feedback to implement appropriate infection prevention and control measures and influence policy. A particularly concerning type of AMR, carbapenem-resistant Enterobacteriaceae, significantly declined after the program was launched. Similarly, there have been no further reports or outbreaks of another concerning type of AMR, colistin resistance in Acinetobacter, in the Department of Defense since the program was initiated. However, AMR-encoding genes appear to be increasing. To update program stakeholders and other healthcare systems facing such challenges, we describe the processes and impact of the program.


Meddaugh, P., & Chukwuma, U. (2015). Multidrug-Resistant Gram-Negative Bacterial and Carbapenem-Resistant Enterobacteriaceae Infections in the Department of the Navy: Annual Report 2013. Portmouth: Navy and Marine Corps Public Health Center.

http://www.dtic.mil/dtic/tr/fulltext/u2/a614086.pdf

Abstract: Gram-negative bacterial infections are a growing global public health and clinical concern. Additionally, epidemics of multidrug-resistant (MDR) gram-negative bacteria have occurred worldwide in the last couple decades, including regions where United States (US) military forces are regularly deployed. In 2013, the incidence of MDR Escherichia coli, Enterobacter, Klebsiella, and Pseudomonas aeruginosa in Department of Defense (DOD) beneficiaries seeking care in the Military Health System (MHS) increased from 2012. MDR E. coli was the organism most frequently identified with an incidence 37-40 times higher than the next most frequent organism. A pronounced gender disparity was noted for all organisms except MDR P. aeruginosa. Overall, DOD female beneficiaries were impacted much more than their male counterparts. Furthermore, MDR E. coli, MDR Enterobacter, and MDR Klebsiella cases commonly manifested as urinary tract infections (UTIs), which is consistent with historic observations. In 2013, cases of MDR P. aeruginosa more commonly manifested as respiratory infections, which is also consistent with historic observations. MDR P. aeruginosa did not display any consistent high susceptibilities at the population level.


Spencer, J., & Chukwuma, U. (2015). Methicillin-Resistant Staphylococcus aureus (MRSA) Infections in the Department of Defense (DOD): Annual Summary 2013. Portsmouth: Navy and Marine Corps Public Health Center.

http://www.dtic.mil/dtic/tr/fulltext/u2/a612614.pdf

Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) infections are a national concern for public health and hospital officials due to the opportunistic nature of the bacteria and the emergence of resistance to several antibiotics. In 2013, the MRSA incidence rates were 58.7 and 73.0 per 100,000 persons per year in the Department of Defense (DOD) and the Department of the Navy (DON) beneficiary populations, respectively; this is a 59% decrease for the DOD and DON since 2005. The majority of MRSA infections within the DOD and DON in 2013 were outpatient, community-associated (CA), and skin and soft tissue infections (SSTIs); similar patterns were observed since 2005. In the DOD from 2005-2013, MRSA isolates showed decreased susceptibility to cefazolin. However, MRSA showed increased susceptibility to erythromycin and cefotaxime in both the DOD and the DON, and to gentamicin in the DON only. The proportion of MRSA cases with inducible clindamycin resistance is increasing, with a 31.3% increase in the DOD and a 65.3% increase in the DON from 2005 to 2013. Military prescription practices in 2013 were consistent with treatments recommended by the Infectious Diseases Society of America (IDSA).


Emil Lesho, Philip Carling, Eve Hosford, Ana Ong, Erik Snesrud, Michael Sparks, Fatma Onmus-Leone, Nicole Dzialowy, Susan Fraser, Yoon Kwak, Sonia Miller, Uzo Chukwuma, Michael Julius, Patrick McGann, and Robert Clifford. Relationships Among Cleaning, Environmental DNA, and Healthcare-Associated Infections in a New Evidence-Based Design Hospital.
Infection Control & Hospital Epidemiology.
Available on CJO 2015 doi:10.1017/ice.2015.151.

Environmental DNA and HAI, ICHE Journal

Abstract: Hospital environments influence healthcare-associated infection (HAI) patterns, but the role of evidenced-based design (EBD) and residual bacterial DNA (previously thought to be clinically inert) remain incompletely understood. In a newly built EBD hospital, we used culture-based and culture-free (molecular) assays, pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing (WGS) to determine: (1) patterns of environmental contamination with target organisms (TOs) and multidrug-resistant (MDR) target organisms (MDR-TOs); (2) genetic relatedness between environmentally isolated MDR-TO and those from HAIs; and (3) correlation between surface contamination and HAIs. A total of 1,273 high-touch surfaces were swabbed before and after terminal cleaning during 77 room visits. Of the 2,546 paired swabs, 47% had cultivable biomaterial and 42% had PCR-amplifiable DNA. The ratios of TOs detected to surfaces assayed were 85 per 1,273 for the culture-based method and 106 per 1,273 for the PCR-based method. Sinks, toilet rails, and bedside tables most frequently harbored biomaterial. Although cleaned surfaces were less likely to have cultivable TOs than precleaned surfaces, they were not less likely to harbor bacterial DNA. The rate of MDR-TOs to surfaces swabbed was 0.1% (3/2546). Although environmental MDR-TOs and MDR-TOs from HAIs were genetically related by PFGE, WGS revealed that they were unrelated. Environmental levels of cultivable Enterococcus spp. and E. coli DNA were positively correlated with infection incidences (P< .04 and P<.005, respectively). MDR-TOs were rarely detected during surveillance and were not implicated in HAIs. The roles of environmental DNA and EBD, particularly with respect to water-associated fixtures or the potential suppression of cultivable environmental MDR-TOs, warrant multicenter investigations.


Chandrasekera, R. M., Lesho, E. P., Chukwuma, U., Cummings, J. F., & Waterman, P. E. The State of Antimicrobial Resistance Surveillance in the Military Health System: A Review of Improvements Made in theLast 10 Years and Remaining Surveillance Gaps.
AMSUS - Association of Military Surgeons of the U.S. doi:10.7205/MILMED-D-14-00297
Portsmouth: Navy and Marine Corps Public Health Center.

http://publications.amsus.org/doi/full/10.7205/MILMED-D-14-00297

Abstract: During a military public health laboratory symposium held in 1999, concerns were raised that the military health system lacked a standardized antimicrobial resistance (AMR) surveillance system that allowed comparison of data across sites, investigation of trends, and understanding of resistance mechanisms. The purpose of this review was to assess if current AMR activities in the military health system have addressed the aforementioned gaps. It was determined that much progress has already been made within the Department of Defense with respect to monitoring and understanding AMR through initiatives such as the Antimicrobial Resistance Monitoring and Research Program—a strong Department of Defense-wide surveillance program. These surveillance efforts can be made more robust through harmonization of testing and reporting structures across military treatment facilities, and by encouraging military treatment facility participation


Lesho Emil P., Clifford Robert J., Chukwuma Uzo, Kwak Yoon I., Maneval Mark, Neumann Charlotte, Xie Suji, Nielsen Lindsey E., Julius Michael D., McGann Patrick, Waterman Paige E.,Carbapenem-resistant Enterobacteriaceae and the Correlation between Carbapenem and Fluoroquinolone Usage and Resistance in the U.S. Military Health System, Health. Diagnostic Microbiology and Infectious Disease (2014), doi: 10.1016/j.diagmicrobio.2014.09.017

CRE DMID Journal

Abstract:Whether carbapenem or fluoroquinolone usage is correlated with carbapenem resistant Enterobacteriaceae has not been investigated at the level of an entire U.S. nationwide managed healthcare system. We analyzed 75 million person-years of surveillance and 1,969,315 cultures from all 266 hospitals in the geographically dispersed U.S. Military Health System. Incidences of CRE remained under 1 case per 100,000 person-years. Incidences of CRE increased relative to 2005 baseline levels in 3 of 7 subsequent years, then decreased in 2012 (P < 0.05). Incident proportions of carbapenem resistance differed significantly among years, geographical regions, and bacterial species. Although use and resistance strongly correlated (R >0.80) for several 'drug-bug' combinations, none were significant at the national or facility level. One exception was that inpatient consumption of fluoroquinolones was significantly correlated (P = .0007) with carbapenem resistance in E. coli when data from the major referral centers of the Southern and Northern regions were combined.


Dzialowy, N., Schaller, E., & Chukwuma, U. (2014). Vancomycin-Resistant Enterococci Infections in the Department of Defense: Annual Report 2013. Portsmouth: Navy and Marine Corps Public Health Center.

http://www.dtic.mil/dtic/tr/fulltext/u2/a609399.pdf

Abstract: Vancomycin-resistant Enterococci (VRE) are Gram-positive cocci that are resistant to vancomycin and most commonly infect seriously ill patients that have prolonged hospital stays or antibiotic use. Hospital acquired VRE infections are associated with high rates of morbidity and mortality and are a concern for hospitals around the world. The objective of this annual retrospective report is to summarize the VRE infection burden in the Department of Defense (DOD) and the Department of the Navy (DON) for calendar year (CY) 2013. This summary includes demographic and clinical characteristics, antibiotic susceptibility patterns, prescription practices, and healthcare-associated (HA) infection metrics for all DOD and DON beneficiaries. Overall, the incidence rates of VRE infections in the general United States (US), DOD, and DON populations are decreasing. VRE risk groups did not substantially change in 2013 as VRE continues to predominately affect elderly females and manifest as urinary tract infections (UTIs). In addition, antibiotic susceptibility patterns did not substantially change in 2013. Linezolid, gentamicin, and streptomycin remain viable treatments for VRE. Although current infection control practices seem to be decreasing the overall burden of VRE, HA infections are still a major problem for transmission of VRE in the DOD and the DON. Improved infection control practices would help to minimize the spread of these infections.


Meddaugh, P., & Chukwuma, U. (2014). Acinetobacter Species Infections among Navy and Marine Corps Beneficiaries: 2013 Annual Report. Portsmouth: Navy and Marine Corps Public Health Center.

http://www.dtic.mil/dtic/tr/fulltext/u2/a611595.pdf

Abstract: Since the early 2000s, health professionals increasingly are concerned about Acinetobacter species infections due to demonstrated ability to develop resistance to multiple antibiotics, limiting treatment options. In 2013, Acinetobacter incidence was 5.5 and 4.4 per 100,000 persons per year in the Department of the Navy (DON) and the Department of Defense (DOD), respectively, continuing previously observed descending trends. Active duty Marines had a higher prevalence rate than any other group of service members. A. baumannii was the most common etiologic agent in 2013 was, differing slightly from 2012. In the DON, a negligible increase in overall resistance was noted, though there was an increase in XDR cases. For non-MDR cases in the DON and DOD, providers often prescribed trimethoprim/sulfamethoxazole, consistent with 2012 observations. For MDR/XDR cases in 2013, DON providers most commonly prescribed colistin, minocycline, piperacillin/tazobactam, and trimethoprim/sulfamethoxazole. DOD providers most commonly prescribed ciprofloxacin for these cases. Although different from 2012, 2013 prescribing patterns were consistent with recommendations. Among DON and DOD beneficiaries respectively, organisms were most susceptible to cefepime and gentamicin while least susceptible to ampicillin and nitrofurantoin; consistent with observations for the DON and DOD from 2012.


Meddaugh, P., & Chukwuma, U. (2013). Acinetobacter Species Infections among Navy and Marine Corps Beneficiaries: 2012 Annual Report. Portsmouth: Navy and Marine Corps Public Health Center.

http://www.dtic.mil/dtic/tr/fulltext/u2/a591862.pdf

Abstract: Acinetobacter species are associated with a large number of infections, have the ability to easily acquire resistance determinants, and quickly develop resistance to multiple antibiotics, leaving few, if any, treatment options. In calendar year (CY) 2012, the overall Acinetobacter infection rate was 5.3 per 100,000 beneficiaries in the Department of the Navy (DON) and 4.8 per 100,000 beneficiaries in the Department of Defense (DOD); both rates decreased from previous years. Acinetobacter among DON beneficiaries was most frequently identified in the outpatient setting (76.7% ), from non-sterile body sites (61.3%), and among 18-24 year olds (36.0%). The most common species identified was A. baumannii (42.7%). Multidrug-resistant (MDR) organisms accounted for 9.3% of DON cases and extensively drug-resistant (XDR) organisms accounted for 1.3% of DON cases. For non-MDR cases in the DON, providers most commonly prescribed trimethoprim/sulfamethoxazole, followed by ofloxacin. For MDR/XDR cases, providers most commonly prescribed vancomycin, meropenem, or doxycycline. Cases with susceptibility testing results showed that, among DON beneficiaries, organisms were most susceptible to gentamicin (92.4%), followed by imipenem (91.2%), and levofloxacin (90.0%); organisms were least susceptible to ampicillin (7.0%). Surveillance of Acinetobacter cases will continue along with quarterly and annual reports to monitor trends and burden in the DON and DOD.


Lesho, E. P., Waterman, P. E., Chukwuma, U., McAuliffe, K., Neumann, C., Julius, M. D., . . . Kester, K. E. (2014). The Antimicrobial Resistance Monitoring and Research (ARMoR) Program: the Department of Defense's Response to Escalating Antimicrobial Resistance. Oxford University Press on behalf of the Infectious Diseases Society of America 2014.

http://cid.oxfordjournals.org/content/early/2014/05/01/cid.ciu319.full.pdf+html

Abstract: Responding to escalating antimicrobial resistance (AMR), the US Department of Defense implemented an enterprise-wide collaboration termed the Antimicrobial Resistance Monitoring and Research Program to aid in infection prevention and control. It consists of a network of epidemiologists, bioinformaticists, microbiology researchers, policy-makers, hospital-based infection preventionists, and healthcare providers who collaborate to collect relevant AMR data, conduct centralized molecular characterization, and use AMR characterization feedback to implement appropriate infection prevention and control measures and influence policy. A particularly concerning type of AMR, carbapenem-resistant Enterobacteriaceae, significantly declined after the program was launched. Similarly, there have been no further reports or outbreaks of another concerning type of AMR, colistin resistance in Acinetobacter, in the Department of Defense since the program was initiated. However, AMR-encoding genes appear to be increasing. To update program stakeholders and other healthcare systems facing such challenges, we describe the processes and impact of the program.


Stephanie M. Morrison, Carl R. Blaesing, Eugene V. Millar, Uzo Chukwuma, Carey D. Schlett, Kenneth J. Wilkins, David R. Tribble and Michael W. Ellis (2013). Evaluation of Methicillin-Resistant Staphylococcus aureus Skin and Soft-Tissue Infection Prevention Strategies at a Military Training Center. Infection Control, 34, pp 841-843 doi:10.1086/671278

MRSA SSTI Journal

Abstract: Military trainees are at high risk for skin and soft·tissue infections (SSTis), especially those caused by methicillin-resistant Staphylo­ coccus aureus (MRSA). A multicomponent hygiene-based SSTI prevention strategy was implemented at a military training center. After implementation, we observed 30o/o and 64o/o reductions in overall and MRSA-associated SSTI rates, respectively.