Prevalence of Methicillin-Resistant Staphylococcus aureus in a Combat Support Hospital in Iraq

Transcription

1 MILITARY MEDICINE, 176, 1:89, 2011 Prevalence of Methicillin-Resistant Staphylococcus aureus in a Combat Support Hospital in Iraq CPT Edgie-Mark Co, MS USA * ; CPT Edward F. Keen III, MS USA ; LTC Wade K. Aldous, MS USA ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) in health-care settings results in life-threatening infections. We examined the incidence of MRSA at the combat support hospital located at the Ibn Sina Hospital in Baghdad, Iraq. We compiled isolate data from 2005 to 2009 characterizing antibiotic susceptibilities, annual trends, patient populations, infection sites, and hospital locations. Approximately 46.1% of S. aureus were MRSA, with increase in numbers of yearly isolates. MRSA was isolated in higher numbers from U.S. military personnel. Non-U.S. patient isolates displayed higher antibiotic susceptibility compared to U.S. military personnel isolates. Outpatient clinic, forward operating bases, and intermediate care ward 1 isolated the most MRSA. Common isolation sites were wound and skin cultures. Community-acquired MRSA was likely present in 291 out of 303 isolates based on antibiotic susceptibility. Our data suggests that most MRSA were community-acquired with limited nosocomial spread. We recommend increases in combat support hospital molecular lab capability to rapidly identify both MRSA categories. INTRODUCTION Methicillin-resistant Staphylococcus aureus (MRSA) is a growing problem because of its propensity to cause medical complications and more alarmingly its resistance to all penicillin-class antibiotics. 1 Two sources of MRSA infections have been identified: community acquired MRSA (CA-MRSA) and hospital acquired MRSA (HA-MRSA) infections. CA-MRSA is categorized as being resistant to methicillin and oxacillin, but susceptible to many nonβ-lactam antibiotics including clindamycin, tetracyclines, and trimethoprim-sulfamethoxazole.2 This category of MRSA has been implicated in many community outbreaks, particularly in training settings such as schools and initial entry military facilities. 3 6 CA-MRSA has also been implicated in 60% of all skin infections seen in U.S. emergency departments. 7 Furthermore, CA-MRSA also includes isolates from individuals who have no predisposing factors to isolation of HA-MRSA. 2 Many studies have addressed the prevalence, risk factors, and complications of MRSA in the military setting, 8 12 specifically in military recruits. 5,6,13 Some have also reported on long-term epidemiology in military personnel, 8 with studies by Crum et al examining a large sample size over an extended period of time (15 years). 13 They found the incidence of CA-MRSAs dramatically increase since 2002, as well as the corresponding hospitalization rate at 16%. Close contact between individuals and unsanitary conditions were speculated to contribute to transmission of the organism. 6,13 *Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD Laboratory Services, 28th Combat Support Hospital, Sather Air Base, APO, AE Department of Pathology and Area Laboratory Services, Brooke Army Medical Center, 3851 Roger Brooke Drive, Fort Sam Houston, TX The opinions or assertions contained herein are our private views and are not to be construed as official or as reflecting views of the Department of the Army or the Department of Defense. More recent investigations focused on incidence in personnel deployed to and returned from Operations Iraqi Freedom and Operations Enduring Freedom. Murray et al studied the recovery of multidrug-resistant bacteria from combat personnel evacuated to Brooke Army Medical Center and found MRSA to be one of the commonly isolated organisms. 14 In addition, Roberts et al examined MRSA incidence from skin and softtissue infections, finding that 70% of S. aureus isolates were MRSA. 15 These studies emphasize the importance of MRSA in the military environment. The 10th Combat Support Hospital (CSH) in Baghdad, Iraq, provides care to U.S. military and coalition personnel, Department of Defense civilians, foreign national contract employees, and Iraqi nationals. Previous studies indicated that S. aureus strains isolated from this facility had elevated resistance patterns to penicillins, but remain susceptible to non-β-lactam antibiotics, 16,17 suggesting higher occurrence of CA-MRSA. However, both studies were conducted for a year and 48 months, with a limited number of strains. More importantly, no analysis was made describing the MRSA incidence rate in the host nation population. This information is of vital importance as U.S. military medical personnel continue to engage with and treat non-u.s. patients. Knowledge of MRSA incidence in our facility will contribute to establishing improved infection control policies and procedures. Furthermore, a more immediate benefit of this study is to inform incoming medical personnel of the antibiotic susceptibility baseline of S. aureus in the facility, which will in turn guide empiric therapy. We describe our facilities MRSA prevalence rate, providing our healthcare providers a survey of multidrug-resistant S. aureu s. We performed retrospective and descriptive analyses of all S. aureus strains isolated in our facility between August 2005 and December 2009, analyzing susceptibility profiles, sources of infection, requesting locations in the hospital, and relative incidence of CA- and HA-MRSA strains. We also tracked yearly trends of MRSA incidence. MILITARY MEDICINE, Vol. 176, January

2 METHODS Facilities and Patient Population Facilities and populations were previously described by Yun et al. 16 Patients were seen at the Ibn Sina hospital tertiary care facility in Baghdad, Iraq, which treated a wide variety of patient populations including U.S. military personnel, U.S. civilians, coalition forces, foreign national contract employees, Iraqi local nationals, and detainees. Furthermore, the hospital provided a spectrum of surgical, intensive, emergent, and outpatient care. The co-located outpatient clinic provided specialty services such as dermatology and physical therapy. Length of hospitalization depended on the needs of the patient, whether they could be rapidly treated or evacuated to a facility with a higher level of care. U.S. service members requiring long-term care were evacuated once they were stabilized, usually within hours. In contrast, many local national patients remained longer until they could be transferred to a local facility. Some of these patients remained in the hospital for up to 2 months. Data Analysis of Recovered MRSA Culture and susceptibility data were acquired via the hospital s laboratory information system from August 2005 to December Positive S. aureus cultures were organized by year, sample source, hospital location, and antibiotic susceptibility. Sample sources listed as other were excluded from statistical analysis, but were included in the overall MRSA rate determination. Yearly rates were normalized for the year 2005 where the laboratory information system had only partial isolate records. CA-MRSA was defined as displaying susceptibility to any of the following three drugs: clindamycin, tetracycline, and trimethoprim-sulfamethoxazole. 2 This criterion was used because testing was limited in this facility (i.e., the CSH lacks capability to perform Pulse Field Gel Electrophoresis [PFGE] or Panton-Valentine leukocidin testing). HA-MRSA was defined as isolates that are resistant to all three drugs. Furthermore, MRSA fitting the hospitalacquired resistance criteria were examined for patient s length of stay at the facility, which was a risk factor as previously described.18 MRSA isolation and identification were performed by normal bacterial identification procedures from blood, body fluid, genital, respiratory, skin, and wound cultures as described previously. Gram staining, Staphaurex (Remel) latex aggluti- 16 nation, and MicroScan PBPC20 (Siemens Healthcare) panels were used for definitive identification and susceptibility testing of staphylococci. Statistical Analyses Data were compared using Fisher s exact test and Wilcoxon rank-sum analyses. A p value of <0.05 was used to indicate statistical significance between groups; all reported p values were two-tailed. RESULTS Antimicrobial Susceptibilities Drug susceptibilities of U.S. and non-u.s. patients to S. aureus isolates are listed in Table I. Strains from U.S. military were less susceptible to antibiotics compared to the non- U.S. patients. Isolates from U.S. military personnel were more resistant to β-lactam antibiotics and erythromycin (40%). The overall hospital MRSA rate was 46%. Most of the S. aureus isolates were susceptible to the non-β-lactam agents. Eightyfour percent of isolates were susceptible to clindamycin. All isolates were susceptible to vancomycin. Table II lists the susceptibility profiles of the MRSA isolates only. As expected, a vast majority of the strains are resistant to β-lactam antibiotics. TABLE I. Susceptibility Profile of Staphylococcus aureus Isolates Number of Susceptible Strains a (%) U.S. Military ( n = 505) Non-U.S. ( n = 152) Cefazolin 247 (49) 98 (64) Ceftriaxone 256 (51) 100 (66) Cephalothin 244 (48) 95 (63) Chloramphenicol 493 (98) 139 (91) Ciprofloxacin 349 (69) 111 (91) Clindamycin 419 (83) 122 (80) Erythromycin 198 (39) 90 (59) Gentamicin 477 (94) 199 (78) Ofloxacin 341 (68) 108 (71) Oxacillin 254 (50) 99 (65) Rifampin 480 (95) 137 (90) Tetracycline 412 (82) 96 (63) Trimeth/Sulfate 490 (97) 120 (79) Vancomycin 505 (100) 152 (100) Amx/K Clavulanate 233 (44) 87 (57) a n = 657 TABLE II. Susceptibility Profile of MRSA Isolates Number of Susceptible Strains (%) a Cefazolin 2 (0.66) Ceftriaxone 4 (1.3) Cephalothin 4 (1.3) Chloramphenicol 287 (95) Ciprofloxacin 147 (48.8) Clindamycin 226 (75.1) Erythromycin 46 (15.4) Gentamicin 265 (88.6) Ofloxacin 146 (48.7) Oxacillin 0 (0) Rifampin 275 (91.4) Tetracycline 236 (80.3) Trimeth/Sulfate 273 (91) Vancomycin 303 (100) Amx/K Clavulanate 3 (1) a n = MILITARY MEDICINE, Vol. 176, January 2011

3 Yearly Trend of MRSA Detection The MRSA isolation rate at the CSH increased annually ( Fig 1 ). Annual numbers of isolated S. aureus did not vary substantially from 2006 to 2008 ( n = 161 ± 5.9). The incidence rate for 2009 data demonstrated a decrease in S. aureus isolation because of a lower patient workload. However, there was still a modest increase in the MRSA isolation rate. Requesting Hospital Locations The identification of MRSA from individual locations in the hospital was mainly from the out-patient clinic, followed by intermediate care ward (ICW) 1 and forward operating bases (FOBs; Fig 2 ). Specimens from the operating room/ central material services (OR/CMS) and ICW2 isolated the least amount of MRSA. The majority of outpatient isolates came from U.S. service members compared to the fewer inpatient isolates mainly from non-u.s. (local national) patients. FIGURE 1. Percentage of total MRSAs isolated by year: August 2005 to December Percentage was calculated by dividing the number of all MRSAs isolated by the number of total S. aureus isolated in the CSH that year. N represents number of MRSA isolates for that year. FIGURE 2. Numbers of MRSA isolated by Hospital Location. EMT: Emergency Medical Treatment, FOB: Forward Operating Base, ICU: Intensive Care Unit, ICW1/2: Intermediate Care Ward 1/2, OPC: Out-Patient Clinic, OR/CMS: Operating Room/Central Material Services. Sources of Infection A total of 505 and 152 S. aureus were isolated from U.S. military personnel and non-u.s. patients, respectively. Table II shows MRSA isolated by body site and by patient population. A total of 303 MRSA were isolated and characterized from 2006 to Two hundred fifty one MRSA strains were isolated from U.S. patients compared to 52 isolates from non-u.s. patients, with a prevalence of 49.7% and 34.2%, respectively. Our statistical analysis shows that U.S. military were twice as likely to be colonized by MRSA compared to non-u.s. patients ( Table II ). Most of the isolates came from surface wounds and skin samples. The overall differences observed between the two populations with regards to specimen sites were statistically significant as shown in Table III. CA- and HA-MRSA Relative Incidence We determined that 291 of 303 isolates were communityacquired based on their susceptibility profiles. The remaining 12 isolates were concurrently resistant to clindamycin, tetracycline, and trimethoprim-sulfamethoxazole, which we concluded to be hospital-acquired strains. All of the HA-MRSA strains were isolated from patients hospitalized from 7 to 82 days, with all isolates coming from non-u.s. patients. DISCUSSION In this study, we describe the incidence of MRSA isolation in a CSH. We determined the MRSA incidence in our facility while generating our hospital antibiogram in support of our healthcare providers to more effectively treat their patients. Most of our providers initially suspected MRSA at first presentation because of nonavailability of prevalence data in our facility, which led to substantial empiric therapy. Thus, we determined the baseline of MRSA prevalence to better inform incoming healthcare providers. This study represents the longest survey of MRSA incidence performed in an Army CSH in Iraq. Drug susceptibility analysis of the S. aureus isolates from our facility indicates a higher resistance pattern to β-lactam and fluoroquinolone class of antibiotics from U.S. military service members ( Table I ). Additionally, U.S. military isolates TABLE III. Total Numbers of MRSA isolated by body site U.S. Patients Non-U.S. Patients Odds Ratio (95% CI) MRSA ( ) Blood 13 3 (50) 10 (52.6) Not Significant Body Fluid 5 4 (21.1) 1 (16.7) 1.33 ( ) Respiratory 16 5 (23.8) 11 (40.7) Not Significant Skin (54.5) 7 (24.1) 3.76 ( ) Wound (49.5) 21 (22.2) 1.9 (1.1 4) Number in parentheses indicates percentage of MRSAs isolated from the particular body site and population. Odds ratio was deemed significant if it was greater than 1 and if the lower bound of the confidence interval was equal or greater than 1. MILITARY MEDICINE, Vol. 176, January

4 were more resistant to erythromycin (60% resistant), a finding similar to Beilman s, indicating a high likelihood of inducible clindamycin resistance in these isolates. 8 Before 2007, the common microbiology assay (D test 19 ) to identify this resistance pattern was not available in theater. Fortunately, very few of those isolates tested after this period presented with this inducible pattern (data not shown). We noted increased susceptibility among our S. aureus isolates to trimethoprim/ sulfamethoxazole and rifampin (100% of MRSA susceptible), which is similar to previous findings. 15 We observed a rising trend of MRSA incidence in our facility ( Fig 1 ) compared to previously reported studies in the US and Iraq. MRSA prevalence rates in the US gradually increased from 1% in the early 1990s 20 to as high as 60% in the mid 1990s. 18 This indicates an upward trend in colonization and infection especially in soft tissue and skin infections, which was also noted in by Moran et al. 21 With continuing resistance rates nationally and throughout the world, this is one of the reasons that MRSA screening in U.S.-run healthcare facilities is now a National Patient Safety Goal. 22 When we analyzed MRSA rates by location, most strains were from the out-patient clinic, FOBs, and ICW1, revealing that these MRSA strains were mostly community-acquired. In fact, several of the wound and skin cultures originated from dermatological consults. Patient presentation ranged from skin infections (cellulitis) to penetrating trauma and burn-related injury wounds. Cultures submitted from the FOBs consisted all wound and skin specimens, also suggesting a communityacquired origin. 6,13,15 Our hospital segregated patients by U.S. military (ICW1) and non-u.s. personnel (ICW2) for both infection control and security reasons. The ICWs were transient in nature, especially in the ICW1, which discharged as many as patients in a day. In comparison, ICW2, which housed the non-u.s. patients, had a slower rate of patient transfer. This likely resulted in a reduced nosocomial transmission and a consequently lower incidence rate of MRSA. Although recent literature indicates that prolonged hospitalization may lead to hospital acquisition of resistant organisms, 5,22 24 the lower MRSA rate in our ICW2 suggests minimal nosocomial transmission between the 2 wards, demonstrating that outstanding infection control procedures were in place. We categorized the isolates by CA-MRSA and HA-MRSA according to commonly accepted susceptibility profiles to the non-β-lactam antibiotics clindamycin, tetracycline, and trimethoprim-sulfamethoxazole.2 We note that HA-MRSA occurred at very low levels (4% of MRSA) in our facility. In a similar study involving a level 2 military treatment facility that treated an outpatient population, all the cases identified were community-acquired infections. 15 Ideally, molecular techniques such as PFGE and detection of the Panton-Valentine leukocidin exotoxin are preferred, 25 but not readily available in a deployed setting. Furthermore, these particular techniques are often time-consuming, highly technical, and susceptible to operator error. Even with the rapid agglutination kit and routine bacterial identification procedures, the minimum turn-around time for MRSA identification is 24 hours. We use the MicroScan PBPC20 panels (Siemens; Deerfield, IL) to measure oxacillin resistance, but are exploring other viable rapid options. One method is detection using real-time polymerase chain reaction (RT-PCR), which can confirm carriage or infection in a few hours and has higher sensitivity compared to culture methods. 26 We therefore recommend augmentation of level III facilities with an RT-PCR instrument that can withstand fielding in austere conditions. For instance, our lab is currently equipped with a Smartcycler RT-PCR (Cepheid; Sunnyvale, CA) and Joint Biological Agent Identification and Diagnostic System (Idaho Technology; Salt Lake City, UT) instruments capable of avian and novel swine-like H1N1 influenza diagnosis, respectively. The H1N1 influenza assay specifically was a nonstandard assay that was granted emergency use authorization in light of the influenza pandemic threat. 27 A similar assay for CA-MRSA could be fielded and validated to allow for shorter turn-around times. These molecular assays are capable of rapidly identifying pathogens and resistance genes within turnaround time as low as 4 hours. 25,28,29 Alternatively, laboratory personnel can examine drug susceptibility profiles and determine MRSA categories. This examination allows the laboratory to advise healthcare providers on categories of MRSA seen in the facility. There was a perception among our healthcare providers that a high prevalence of multidrug-resistant organisms existed in the local host nation population because of the perceived availability of antibiotics in the black market and the consequent emergence of highly drug-resistant organisms. However, our statistical analysis shows that U.S. military personnel are twice as likely to present with MRSA compared to non-u.s. individuals. In contrast, the non-u.s. patient population (mostly Iraqi host nationals) is not initially predisposed to MRSA. Although this patient population is perceived as using unprescribed antibiotics (personal communications), a majority of them do not initially present with MRSA infections. However, these patients typically remain hospitalized longer than the U.S. military personnel, predisposing them to acquisition of other multidrug-resistant organisms because of nosocomial spread. 22 This finding is significant because no previous MRSA incidence data were available for the local population. This lack of epidemiological data is detrimental to the ongoing military mission in medical facilities that treat local patients. To our knowledge, this study is the first description of MRSA incidence and susceptibility data in the Iraqi local population. Efforts are underway to characterize collected strains using PFGE. Future studies will address endemicity of HA-MRSA in host nation personnel because it is unclear if these highly resistant MRSA arise from initial colonization, nosocomial transfer, or development from de novo mutations. 30 Genetic analyses can determine the evolution of these strains. For the laboratory s part, because of the requirement of additional equipment and personnel to perform PFGE, this procedure is 92 MILITARY MEDICINE, Vol. 176, January 2011

5 not conducive to being performed in the CSH. Fortunately, we are collaborating with the U.S. Army Institute for Surgical Research to determine the interrelatedness of these strains. Nevertheless, we recommend continued laboratory surveillance to ensure documentation of changes in susceptibility trends and promotion of appropriate empiric antibiotic treatment responses. ACKNOWLEDGMENTS The authors would like to thank COL Joseph Pina, COL Peter Weina, and MAJ Devon Reed for their invaluable insights and conversations on this topic. REFERENCES 1. Applebaum PC : MRSA the tip of the iceberg. Clin Microbiol Infect 2006 ; 12 Suppl: Miller G, Kaplan SL: Staphylococcus aureus : a community pathogen. Infect Dis Clin N Am 2009 ; 23: Rihn JA, Michaels MG, Harner CD : Community-acquired methicillinresistant Staphylococcus aureus : an emerging problem in the athletic population. 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