Original Article Vol. 28 No. 1 Surveillance of Antimicrobial Resistance:- Chaiwarith R, et al. 3 Surveillance of Antimicrobial Resistance among Bacterial Pathogens Isolated from Hospitalized Patients at Chiang Mai University Hospital, 6-9 Romanee Chaiwarith, M.D., MHS, Nontakan Nuntachit, M.D., Kaweesak Chittawatanarat, M.D., Manasanant Bunchoo, M.Sc., Khuanchai Supparatpinyo, M.D., Peninnah Oberdorfer, M.D., Ph.D., for the Infection Control Team, Faculty of Medicine, Chiang Mai University. ABSTRACT Background: Conducting surveillance of multidrug-resistant organisms leads to identifying changes in the pathogens causing healthcare-associated infections (HAIs) of specific sites, and the antimicrobial susceptibility patterns. This surveillance study aimed to characterize the pattern of nosocomial multidrug-resistant pathogens. Methods: Clinical laboratory reports from Chiang Mai University hospital were reviewed from 6 to 9. Results: During the 4-year period, gram-negative bacteria were the majority of clinical isolates. A. baumannii was the most common pathogen isolated from sputum. E. coli was the most common pathogen isolated from blood and urine. Carbapenem resistance among A. baumanii isolates was 67.1%, 74.2%, 68.9%, and 74.2% in 6, 7, 8, and 9, respectively. Carbapenem resistance among P. aeruginosa was 3.%, 33.8%, 27.%, and 26.8% in 6, 7, 8, and 9, respectively. Extended-spectrum β- lactamase producing strains accounted for 3.2% and 49.2% among E. coli and K. pneumoniae, respectively in 6 and 3.2% and 6.% in 9. Gram-positive bacteria accounted for 2% of all isolates for all 4 years. S. aureus and Enterococci were the most common gram-positive pathogens. Among S. aureus, 3% and 44% were methicillin-resistant strains in 6 and 9, respectively. Conclusions: The surveillance data showed that gram-negative bacteria are the major problems in our hospital. Multidrug-resistant Acinetobacter baumannii is a particularly important problem. Continued surveillance is essential to monitor the trend of these multidrug-resistant bacteria. (J Infect Dis Antimicrob Agents 11;28:3-44.) Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. Received for publication: January 4, 1. Reprint request: Romanee Chaiwarith, Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. E-mail: rchaiwar@gmail.com Keywords: Surveillance, Nosocomial pathogens, Antimicrobial resistance, Multidrug-resistant A. baumannii, Vancomycin-resistant enterococci, Thailand 3
36 J INFECT DIS ANTIMICROB AGENTS Jan.-April 11 INTRODUCTION Nosocomial infections caused by antimicrobialresistant pathogens have an impact on clinical outcomes including morbidity, mortality, length of hospital stays and costs. 1 The Centers for Disease Control and Prevention (CDC) announced 4 strategies which include 12 steps to prevent antimicrobial resistance. 2 These strategies are as follows: prevent infection, diagnose and treat infection effectively, use antimicrobials wisely, and prevent transmission. Understanding antimicrobial susceptibility patterns at our own institution leads to appropriate empirical antimicrobial therapy. Conducting surveillance for antimicrobial resistance among nosocomial pathogens has multiple purposes: to detect clustering in time and space of infections i.e. outbreaks, to convince clinicians and administrators that there is a potential problem (that may require additional resources), to guide treatment (e.g. the choice of antimicrobial agents) and/ or prevention strategies, to reduce the incidence of healthcare-associated infections (HAIs), and to make comparisons within and between hospitals or healthcare systems. 3 There are networks and organizations conducting surveillance in many regions e.g. the National Health Safety Network (NHSN) in the United States, 4 the International Nosocomial Infection Control Consortium (INICC) among limited resources countries, the Study for Monitoring Antimicrobial Resistance Trends (SMART) in Europe and Asia-Pacific, 6-7 and the National Antimicrobial Resistance Center, Thailand (NARST) in Thailand. 8 We, therefore, conduct the surveillance of antimicrobial resistance among nosocomial pathogens at our hospital to identify changes in pathogens causing HAIs at specific sites, and the antimicrobial susceptibility patterns over time. MATERIALS AND METHODS We analyzed data reported from the central diagnostic laboratory (CDL), Chiang Mai University Hospital. Chiang Mai University Hospital is an 1,8- bed, teaching hospital in Northern Thailand which serves over 4, out-patients and over, in-patients each year. There are 7 intensive care units: medical (3), surgical (1), neurosurgical (1), cardiothoracic (1), pediatric (1); 7 intermediate care units: medical (3), surgical (3), pediatric (1), obstetrics and gynecology (1). All clinical specimens either from infected or colonized hospitalized patients submitted to the CDL for bacterial cultures between January 1, 6 and December 31, 9 were included. The methods used for pathogen identification and antimicrobial susceptibility testing were those put out by the Clinical and Laboratory Standards Institute (CLSI). 9 The susceptibility results were categorized into three groups: sensitive (S), intermediate resistant (I), and resistant (R). For fluoroquinolone susceptibility testing, CDL sometimes tested different antimicrobial agents within the class according to availability at the time of testing; resistance was defined using data from at least one of several agents within the class. We defined resistance to fluoroquinolone among Pseudomonas aeruginosa and Escherichia coli as resistant to either ciprofloxacin, levofloxacin, or ofloxacin. Statistical analysis Data were presented in number (%). All statistical analyses were performed using Stata statistical software version. (Stata Statistical Software: Release., Stata Corporation, College Station, TX, 7). RESULTS Distribution of clinical specimens There were 13, 64, 14, 314, 14, 976, and 16, 97
Vol. 28 No. 1 Surveillance of Antimicrobial Resistance:- Chaiwarith R, et al. 37 clinical specimens submitted to CDL for bacterial cultures during the 4-year period. The majority of specimens were sputum or respiratory specimens including bronchoalveolar lavage (BAL) (31.6%), followed by urine (29.3%), pus (22.8%), blood (7.8%), and cerebrospinal fluid (.7%). Majority of clinical specimens were sent from medical units (39.7%) and surgical units (27.4%). (Table 1) Pathogen distribution Gram-negative bacilli were the majority pathogens isolated from clinical specimens (7%). The three most common pathogens were E. coli, P. aeruginosa, and Acinetobacter baumannii. The most common pathogen isolated from sputum, urine, pus, and blood were A. baumannii, E. coli, Staphylococcus aureus, and E. coli, respectively. (Figure 1) The distribution of pathogens from particular units is shown in Table 1. Antimicrobial Resistance Ceftazidime-resistant P. aeruginosa was found in 41.8%, 36.%, 33.3%, and 34.9% in 6, 7, 8, and 9, respectively (Figure 2). Carbapenemresistant A. baumannii was found in 67.1%, 74.2%, 68.9%, and 74.3% in 6, 7, 8, and 9, respectively (Figure 2). Among carbapenem-resistant A. baumannii, the isolates were susceptible to cefoperazone/sulbactam in 66.% and 93.4% in 6 and 7, and then declined to 37.4% and.% in 8 and 9 (Figure 3). Extended-spectrum β- lactamase (ESBL)-producing Enterobacteriaceae was more prevalent in E. coli than in K. pneumoniae (Figure 4). Carbapenem-resistant E. coli was found in.1,.7,., and % in 6, 7, 8, and 9, respectively. Carbapenem-resistant K. pneumoniae was found in 2.3%, 2.%,.7%, and.9% in 6, 7, 8, and 9, respectively. Methicillin-resistant Staphylococcus aureus was found in 34.8%, 34.8%, 39.%, and 44.3% in 6, Table 1. Percentages of pathogens sent from various departments. Departments A.baumannii P. aeruginosa E. coli K. pneumoniae Medicine* 47. 2 36. 7 3. 4 39. 4 11. 1 7. 3 1. 4 3. 4 Surgery* 27. 2 28. 7 24. 29. 4 8. 9 7. 2. 6 6. 4 Pediatric 13. 1. 4. 3 6. 4 Orthopedics 4. 7. 8 7. 6 4. EENT 1.. 2 1.. 6 OB/GYN. 6. 8 6. 6 2. 6 Total isolates (N) 7,19 8,173 6, 3,293 *Includes general units, intermediate care units, and ;, intensive care unit; EENT, eye ear nose throat; OB, obstetric; GYN, gynecology 37
38 J INFECT DIS ANTIMICROB AGENTS Jan.-April 11 2 1 2 P. aeruginosa A. baumannii K. pneumoniae S. aureus H. influenzae S. maltophilia (a) 1 6 7 8 9 4 3 2 1 E. coli Enterococci K. pneumoniae P. aeruginosa A. baumannii (b) 6 7 8 9 18 16 14 12 8 6 4 2 6 7 8 9 E. coli K. pneumoniae S. aureus A. baumannii P. aeruginosa Coagulase-negative staphylococci (c) Figure 1. Percentages of most common pathogens isolated from sputum (a), urine (b), and blood (c).
Vol. 28 No. 1 Surveillance of Antimicrobial Resistance:- Chaiwarith R, et al. 39 9 8 7 6 4 6 7 8 9 Meropenem Imipenem Piperacillin/tazobactam Cefoperazone/sulbactam Ceftazidime Ciprofloxacin Amikacin (a) 4 4 3 2 1 6 7 8 9 Meropenem Imipenem Piperacillin/tazobactam Cefoperazone/sulbactam Ceftazidime Ciprofloxacin Amikacin (b) Figure 2. Percentages of various antimicrobial resistances for A. baumannii (a), and P. aeruginosa (b). 7, 8, and 9, respectively. Vancomycinresistant enterococci were isolated in 1, 2, and clinical specimens in 6, 7, and 9, respectively. Clinical isolates from the intensive care units (s) and intermediate care units had higher rates of resistance to various antimicrobial agents than clinical isolates from general units (Table 2). Among medical units, susceptibility to various antimicrobial agents for A. baumannii and P. aeruginosa differed by units and years as shown in Figure. DISCUSSION These surveillance data revealed that the most 39 common pathogen from respiratory specimens were A. baumannii. This finding corresponded to the national report from the NARST. 8 Approximately 67-7% of A. baumannii isolates were resistant to carbapenems, which is a broad-spectrum antibiotic covering most of gram-negative and gram-positive bacteria, including anaerobes. This rate was much higher than that reported to the NHSN, the Centers for Disease Control and Prevention, which was 29.2-36.8%. Sulbactam has an intrinsic activity against A. baumannii. 11 However, we do not have sulbactam alone, but in combination with cefoperazone or ampicillin. Cefoperazone/sulbactam had less activity
4 J INFECT DIS ANTIMICROB AGENTS Jan.-April 11 9 8 7 6 4 6 7 8 9 Piperacillin/tazobactam Cefoperazone/sulbactam Ciprofloxacin Amikacin Figure 3. Percentages of various antimicrobial susceptibility among carbapenem-resistant A. baumannii. E. coli K. pneumoniae Figure 4. Percentages of ESBL-producing Enterobacteriaceae. against A. baumanii in the recent years as shown in Figure 2. Carbapenem-resistant A. baumannii were susceptible to cefoperazone/sulbactam in only % in the year 9. Susceptibility to colistin was preserved in almost % for A. baumannii. While waiting for respiratory culture results of hospitalized patients who developed lower respiratory infections in our hospital and whose Gram stain showed gram-negative coccobacilli, coverage of A. baumannii is needed. P. aeruginosa was the second most common pathogen isolated from respiratory specimens. Antimicrobial susceptibility for P. aeruginosa was not as bad as A. baumannii. Carbapenem-resistant was found in around % of clinical isolates, which was higher than the national report of % 8, and was similar to the NHSN and the International Nosocomial Infection Control Consortium (INICC) report.,12 However, the activity of ceftazidime, which had an excellent activity against P. aeruginosa in the past, was diminished. Piperacillin/ tazobactam remained to have good activity against P.aeruginosa. E. coli was the most common pathogen isolated from urine. Over half of them were ESBL-producing
Vol. 28 No. 1 Surveillance of Antimicrobial Resistance:- Chaiwarith R, et al. 41 Table 2. Percentages of antimicrobial susceptibility by departments. Pathoge ns CTZ SUL TZ IMP MER AMK CPO CO A.baumannii Medicine General 22 2 2 29 31 31 22 99 7 7 14 7 99 Intermediate care 38 9 12 11 18 7 99 Sugery General 28 9 39 41 33 26 16 42 17 19 21 26 17 Total* 21 48 23 27 28 28 22 99 P.aeruginosa Medicine General 6 9 83 71 69 69 61 41 44 74 4 42 47 43 98 Intermediate care 41 44 73 49 49 6 44 Surgery General 68 66 82 76 73 78 7 9 6 83 6 61 69 64 99 Total* 62 6 81 67 66 69 6 99 *Total isolates from all departments;, intensive care units; CTZ, ceftazidime, SUL, cefoperazone/sulbactam, TZ, piperacillin/tazobactam, IMP, imipenem; MER, meropenem; AMK, amikacin; CPO, ciprofloxacin; CO, colistin strains. Fortunately, we had only sporadic isolates of carbapenem-resistant E. coli. However, CDL could not perform test to identify whether these isolates expressed carbapenemase enzyme. E. coli was also the most common pathogens isolated from blood. This is different from the national report where coagulase-negative staphylococci were the most common pathogens isolated from blood. 8 The surveillance data from the NHSN also reviewed that coagulase-negative staphylococci was the most common pathogen responsible for central-line 41 associated bloodstream infection (CLABSI). Due to the fact that these were surveillance data, we did not explore whether they were primary or secondary bloodstream infections, and whether or not they were catheter-related bloodstream infection. Gram-positive bacteria were not a major problem in our hospital. However, over % of S. aureus isolates were methicillin-resistant. This rate is slightly higher than the national report which was 23-28% between the years 6-8. 8 However, this rate is much lower than that reported from the
42 J INFECT DIS ANTIMICROB AGENTS Jan.-April 11 9 8 7 6 4 (1) (2) 9 (a) 8 7 6 7 8 9 6 4 6 7 8 9 9 9 8 7 (b) 8 7 6 4 6 7 8 9 6 4 6 7 8 9 9 9 8 8 7 7 6 4 6 7 8 9 6 4 6 7 8 9 Figure. Percentages of various antimicrobial susceptibility for A. baumannii (1a-3a), and P. aeruginosa (1b-3b) in the Department of Medicine, (a) represent general units,(b) represent intensive care units, (c) represent intermediate-care units. CTZ, ceftazidime; SUL, cefoperazone/ sulbactam; TZ, piperacillin/tazobactam; IMP, imipenem; MER, meropenem; AMK, amikacin.
Vol. 28 No. 1 Surveillance of Antimicrobial Resistance:- Chaiwarith R, et al. 43 INICC, which was as high as 8%. 12 Vancomycinresistant S. aureus has never been reported in our hospital. Vancomycin-resistant enterococci (VRE) were reported in sporadic cases, although the number of isolates increased over 4 years. VRE were much more common in the USA. Clinical isolates from the medical and surgical units appeared to be the main source of Gramnegative bacilli. This might be explained by the large number of patients admitted to these units and the fact that these patients were more likely to be in severe conditions than patients admitted to other units. Clinical isolates from the s and intermediate care units were more resistant to various antimicrobial agents than isolates from the general units in both medical and surgical units. This may reflect the selective pressure from higher rate of antimicrobial prescription in these units. 13 Knowing the susceptibility patterns for particular units where patients are hospitalized e.g. s, intermediate care units, or general units is helpful in antimicrobial selection for empirical therapy while waiting for the culture results. The differences in multidrug-resistant pathogens among various reports depends on the study population, the data source reviewed, the study methods, and patterns of antimicrobial use in each setting. These surveillance data identified changes in the pathogens causing HAIs of specific sites, and the antimicrobial susceptibility patterns over time. These data need to be reported to healthcare personnel and also the hospital administrators to convince them to support the strategies to decrease the occurrence and to prevent the transmission of these multidrugresistant bacteria. This is the first step for a further management plan including 1) to establish the infection prevention and control measures for multidrugresistant bacteria, 2) to develop antimicrobial 43 treatment guideline for specific units, 3) to implement intervention to reduce the incidence of HAIs, and 4) to conduct research to fulfill the knowledge gap that may arise. This study does have some limitations. Firstly, these surveillance data were retrieved from the CDL with no clinical information incorporated. Therefore, we did not differentiate between infected and colonized patients. However, this study was focused on the trend of antimicrobial resistance among clinical isolates in the same fashion as NARST, which also do not differentiate between infected and colonized patients. Secondly, some specimens sent from hospitalized patients might represent communityacquired pathogens. However, majority of the pathogens i.e. P. aeruginosa, A. baumannii, ESBLproducing enterobacteriaceae are more likely to represent nosocomial pathogens. CONCLUSIONS The surveillance data showed that gram-negative bacteria are the major problems in our hospital. Multidrug-resistant A. baumannii is an important problem. Carbapenem-resistant Enterobacteriaceae and vancomycin-resistant enterococci were reported sporadically. Continued surveillance is essential to monitor the trend of these multidrug-resistant bacteria, and guide physicians to appropriately prescribe empirical therapy. ACKNOWLEDGEMENT We would like to thank Ms.Kanungnit Nuket for the data management. References 1. Shorr AF. Review of studies of the impact on Gramnegative bacterial resistance on outcomes in the intensive care unit. Crit Care Med 9;37:1463-9.
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