Hospital Acquired Infections in a Medical Intensive Care Unit

ORIGINAL ARTICLE Hospital Acquired Infections in a Medical Intensive Care Unit Naeem Akhtar ABSTRACT Objective: To determine the frequency of nosocomial infections and causative organisms in medical intensive care unit (ICU) patients and antimicrobial susceptibility pattern of the isolates. Study Design: A cross-sectional study. Place and Duration of Study: The Holy Family Hospital, Rawalpindi, during the period of May 2007 to April 2008. Methodology: Clinical samples from patients having any signs of site-specific infections or fever appearing anytime after 48 hours of admission into ICU were collected. The samples were cultured onto suitable culture media and bacterial isolates were identified using standard biochemical methods. Antimicrobial susceptibility testing to conventional and newer antibiotics was performed on Mueller Hinton agar using disc diffusion method. Frequency percentages were determined. Results: Bacteria or Candida spp. were isolated from 269/440 (60.1%) samples. The most frequent site of infection was respiratory tract (47.95%) followed by urinary tract (25.3%). Pseudomonas (P.) aeruginosa, Klebsiella (K.) pneumoniae, Escherichia (E.) coli and Candida spp. were the commonest organisms. The isolation rate of Gram-positive bacteria was relatively low. Majority (> 50%) of the Gram-negative isolates were resistant to many of the antibiotics tested. Relatively low resistance was only observed against amikacin (21.3%) and imipenem (26.1%). Majority (> 60%) of Gram-negative isolates were resistant to cefotaxime, ceftriaxone and ceftazidime. The isolates showed high resistance to ofloxacin (65.9%) and ciprofloxacin (73.9%). Conclusion: The high frequency of HAIs and antibiotic resistance rate, suggests that more strict infection control practices along with prescription of antibiotics after antibiotic susceptibility testing should be implemented to limit the emergence of antibiotic resistant organisms. Key words: Hospital acquired infections. Medical intensive care unit. Antibiotic susceptibility. Prevalent microorganisms. INTRODUCTION Patients in intensive care units (ICUs) have a higher risk of acquiring hospital acquired infections (HAIs) than those in non-critical care areas. 1 ICU-acquired infection rate is five to ten times higher than hospital-acquired infection rates in general ward patients. 2 Considerable increased mortality and major costs are associated with ICU-acquired infections. 3-5 This results from the acute severity of illness of ICU patients, prolonged hospital stay, immunosuppression, increased use of antimicrobials and frequent exposure to therapeutic procedures like endotracheal intubation with mechanical ventilation, nasotracheal intubation, intravenous lines, central venous lines and urinary catheterization. 6-9 The most common HAIs in ICU patients are respiratory tract infections (RTIs), urinary tract infections (UTIs) and bloodstream infections (BSIs) and are most often associated with the use of invasive devices. 7 Both Gram-positive and Gram-negative bacteria and Candida Department of Pathology, Rawalpindi Medical College, Correspondence: Dr. Naeem Akhtar, House No. A-6, Rawalpindi Medical College Staff Colony, Rawalpindi Road, E-mail: naeeakh@yahoo.com Received October 22, 2009; accepted April 14, 2010. spp. have been reported as cause of infection in these patients. 10-12 Recently, Gram-negative bacilli have been reported more frequently than Gram-positives in this setting. 10 The ICUs are an area of considerable antibiotic use in which antibiotic-resistant organisms are prevalent. 13,14 Their prevalence and rates of resistance can vary enormously depending on geographic location as well as location among ICU types. 15 For proper management of ICU-infections, it is important to have updated knowledge about prevalence of the causative agents and their antimicrobial susceptibility patterns in institution-specific ICUs. 16 There are very few published studies on the epidemiology of HAIs in ICU patients from Pakistan. Therefore, this study was carried out to determine the prevalent microorganisms in medical ICUpatients and antimicrobial susceptibility profile of the isolates to the commonly used older and newer antibiotics. METHODOLOGY The study was carried out at the eight-bed medical ICU (MICU) of The Holy Family Hospital in Rawalpindi, from May 2007 to April 2008. The patients were observed for any signs of site-specific infections or fever appearing anytime after 48 hours of admission into ICU. Patients admitted into ICU with any signs of infections were 386 Journal of the College of Physicians and Surgeons Pakistan 2010, Vol. 20 (6): 386-390

Hospital acquired infections in a medical intensive care unit excluded from the study. Clinical specimens including tracheal aspirates, sputum, urine, urine catheter tips, central venous line tips, blood, body fluids, pus and others were collected from the patients and were processed at microbiology laboratory of the hospital. The specimens were cultured onto suitable culture media like MacConkey agar, sheep blood agar, chocolate agar and Sabouraud s agar. Plates were incubated aerobically for 24-48 hours. The isolates were identified by colonial morphology, gram-staining, biochemical tests like catalase, coagulase, oxidase, bile solubility and API-10S (Biomeroux, France). Antimicrobial susceptibility testing was performed on Mueller Hinton agar using disc diffusion method in accordance with Clinical and Laboratory Standard Institute Guidelines. 17 Zone sizes of each antimicrobial agent were recorded and interpreted as resistant, intermediate or susceptible. Intermediately susceptible isolates were considered resistant. Susceptibility was tested against following antimicrobials according to their spectrum of activity against Gram-positive or Gramnegative bacteria. Antimicrobials tested against Grampositive bacteria were: ampicillin, co-amoxiclav, cephradine, cephalexin, cefaclor, cefotaxime, amikacin, gentamicin, tetracycline, chloramphenicol, co-trimoxazole, ofloxacin, ciprofloxacin, vancomycin and imipenem. Methicillin resistance in MRSA was tested using oxacillin discs. Antimicrobials tested against Gramnegative bacteria were co-amoxiclav, cefotaxime, ceftazidime, ceftriaxone, amikacin, gentamicin, tetracycline, chloramphenicol, co-trimoxazole, ofloxacin, ciprofloxacin, imipenem and aztreonam. Microsoft Excel spread sheet was used to analyze the data in the form of percentages. Approval for the study was obtained from Research and Ethics Committee, Rawalpindi Medical College and Allied Hospitals, RESULTS Out of total 440 specimens received, bacteria or Candida spp. were isolated from 269/440 (60.1%) samples. The most frequent site of infection was the respiratory tract (47.95%) followed by urinary tract (25.3%), wounds (8.2%) and blood stream (7.06% BSI). K. pneumoniae (30.2%), P. aeruginosa (28.7%), and E. coli (19.4%) were the commonest organisms isolated from respiratory tract samples. Similarly, K. pneumoniae (25%), E. coli (23.5%), P. aeruginosa (16.2%) and Candida spp. (14.7%), were isolated from urinary tract samples. Organisms causing BSIs were P. aeruginosa (31.6%), E. coli (31.6%), Streptococcus pneumoniae (21.1%), and K. pneumoniae (10.5%). These BSI organisms were isolated from cultures of blood and the central venous line tips. The isolation rate of other Gram-negative bacteria, Staphylococcus (S.) aureus and methicillin-resistant S. aureus (MRSA), was relatively low. Details of the antibiotic resistance pattern in Grampositive and Gram-negative isolates are shown in Table I and Table II respectively. None of the isolates, except vancomycin against Gram-positive isolates, were 100% sensitive to the antibiotics tested. Relatively low resistance was only observed against amikacin (21.3%) and imipenem (26.1%). Resistance in Gram-negative isolates was more marked than in Gram-positive isolates. Resistance to commonly used antibiotics was very high. Majority of the Gram-negative and to a lesser extent, Gram-positive isolates showed > 50% resistance to many of the antibiotics tested. Out of two fluoroquinolones tested, higher resistance was observed in ciprofloxacin (73.9% and 69.2%) than ofloxacin (65.9% and 61.5%) in Gram-negative and Gram-positive isolates respectively. Among third generation cephalosporins tested, >60% of the majority of Gram-negative isolates were resistant. Among the aminoglycosides tested, resistance was higher to gentamicin than amikacin. Table I: Antibiotic resistance pattern of Gram-positive bacterial clinical isolates from patients admitted in medical intensive care unit (MICU). Antibiotics Organisms isolated S. aureus MRSA S. pneumoniae Total (n=13) (n=19) (n=07) (n=39) No resistant No resistant No resistant No resistant (%) (%) (%) (%) Ampicillin 12 (92.3) ---- 04 (57.1) 16 (80)* Co amoxyclav 09 (69.2) 11 (57.9) 03 (42.9) 23 (59) Cephradine 03 (23.1) ---- 02 (28.6) 5 (25)* Cephalexin 06 (46.2) ---- 04 (57.1) 10 (50)* Cefaclor 08 (61.5) ---- 04 (57.1) 12 (60)* Cefotaxime 06 (46.2) ---- 03 (42.9) 9 (45)* Ofloxacin 05 (38.5) 17 (89.5) 02 (28.6) 24 (61.5) Ciprofloxacin 08 (61.5) 17 (89.5) 02 (28.6) 27 (69.2) Amikacin 01 (7.7) 01 (5.3) 01 (14.3) 03 (7.7) Gentamicin 10 (76.9) 16 (84.2) 04 (57.1) 30 (76.9) Tetracycline 08 (61.5) 15 (78.9) 05 (71.4) 28 (71.8) Chloramphenicol 02 (15.4) 10 (52.6) 05 (71.4) 17 (43.6) Co trimoxazole 09 (69.2) 18 (94.7) 02 (28.6) 29 (74.4) Imipenem 07 (53.8) 06 (31.6) 02 (28.6) 15 (38.5) Vancomycin 0 (0) 0 (0) 0 (0) 0 (0) *No (%) of isolates resistant to the tested antibiotic out of total of 20 (S. aureus=13 and S. pneumoniae=07). DISCUSSION HAIs are seen worldwide but are less studied and are given less emphasis in developing countries like Pakistan. This study reports a high rate of HAIs, as well as high antibiotic resistance, in ICU settings of a tertiary care hospital in RTIs (47.95%) and UTIs (25.3%) were the commonest infections from these Journal of the College of Physicians and Surgeons Pakistan 2010, Vol. 20 (6): 386-390 387

Naeem Akhtar Table II: Antibiotic resistance pattern of Gram-negative bacterial clinical isolates from patients admitted in medical intensive care unit (MICU). Antibiotics Organisms Isolated E. coli (n=53) K. pneumoniae (n=72) Citrobacter spp. (n=03) Proteus spp. (n=09) P. aeruginosa (n=74) Total (n =211) No resistant (%) No resistant (%) No resistant (%) No resistant (%) No resistant (%) No resistant (%) Co-amoxiclav 45 (84.9) 60 (83.3) 03 (100) 08 (88.9) 53 (71.6) 169 (80.1) Cefotaxime 33 (62.3) 43 (59.7) 02 (66.7) 05 (55.6) 49 (66.2) 132 (62.6) Ceftazidime 38 (71.7) 34 (47.2) 02 (66.7) 06 (66.7) 63 (85.1) 143 (67.8) Ceftriaxone 38 (71.7) 45 (62.5) 03 (100) 09 (100) 62 (83.8) 157 (74.4) Ofloxacin 40 (75.5) 38 (52.8) 02 (66.7) 04 (44.4) 55 (74.3) 139 (65.9) Ciprofloxacin 40 (75.5) 53 (73.6) 02 (66.7) 05 (55.6) 56 (75.7) 156 (73.9) Amikacin 13 (24.5) 21 (29.2) 02 (66.7) 02 (22.2) 07 (9.5) 45 (21.3) Gentamicin 26 (49.1) 33 (45.8) 01 (33.3) 05 (55.6) 40 (54.1) 105 (49.8) Tetracycline 38 (71.7) 44 (61.1) 02 (66.7) 09 (100) 53 (71.6) 146 (69.2) Chloramphenicol 34 (64.2) 42 (58.3) 02 (66.7) 05 (55.6) 44 (59.5) 125 (59.2) Co -trimoxazole 34 (64.2) 64 (88.9) 02 (66.7) 08 (88.9) 51 (68.9) 159 (75.4) Imipenem 08 (15.1) 15 (20.8) 01 (33.3) 01 (11.1) 30 (40.5) 55 (26.1) Aztreonam 17 (32.1) 05 (6.9) 02 (66.7) 05 (55.6) 45 (60.8) 74 (35.1) patients and this is in agreement with other studies from Pakistan 11,12,18 and other countries. 3,9 In a study conducted at Karachi, the frequency of RTIs and UTI was 21% and 44.6% respectively. 12 In another study carried out at Hyderabad, the frequency of RTIs and UTIs was 30.1% and 39.1% respectively. This difference could possibly be due to the difference in antibiotic prescribing practices and variations in sample collection, culture and susceptibility testing practices. Most RTIs were associated with mechanical ventilation (82.2%) as the later is a major factor for RTIs in ICUs. 1,19 Higher rate of UTIs (25.3%) in these patients is obvious due to chronic illnesses like stroke and diabetes. This was associated with urinary catheterization (67.6%) and prolonged urinary catheterization is a major risk factor for UTIs in ICU patients. 15 These findings are in close agreement with those reported by the U.S. National Nosocomial Infections Surveillance (NNIS) system and local studies. 7,12,18 Relatively lower rate of BSIs (7.06%) in this study as compared to other local studies 23.7% and 27%, 12,18 may partly be due to the reason, that blood cultures were manually processed or primary BSIs are less prevalent in our setting. The relatively high incidence of HAIs observed in this study may be a reflection of the higher severity of illness, poor nutritional status, more interventions, fewer staff, poor adherence to aseptic measures and high proportion of mechanical ventilation. 4,9 Gram-negative bacteria i.e. P. aeruginosa, K. pneumoniae and E. coli were the commonest organisms isolated from RTIs, UTIs and BSIs. This is in agreement with previous studies from Pakistan 12,20 and other countries. 9,10 Prevalence of other Gram-negative bacteria, S. aureus and MRSA is relatively low as in general Gram-negative bacterial infections are increasing in ICUs than Grampositive bacterial infections. 10,21 A markedly higher isolation rate of Candida spp. from UTIs is in agreement with other report from US NNIS, 22 but in present study this was not associated with urinary catheterization. In this study the most commonly used antibiotics belonging to penicillins, cephlosporins, fluoro-quinolones, aminoglycosides, co-trimoxazole and carbapenems were tested against the bacterial isolates to have an update current status of the resistance pattern. The higher resistance in these patients is probably due to different antibiotic prescribing practices as it varies enormously. 23 Very high resistance rate to the most commonly used antibiotics including; fluoroquinolones is most likely due to misuse, overuse and over-the-counter availability of these antibiotics. HAIs particularly in ICUs admitted patients who are at higher risk get primary infection with multi-resistant organisms. This makes the treatment of these infections progressively more complicated 16 and is also associated with increased patient charges or hospital costs and mortality. 5 Furthermore, a major contributing factor to this increased resistance is use of the antibiotics without culture and susceptibility testing as even basic facilities for culture and antibiotic susceptibility testing are not available at majority of healthcare settings in our set up. Relatively lower resistance rate to imipenem and amikacin is probably due to lesser use of these antibiotics and is in agreement with another local study. 12 Vancomycin remains the only option for MRSA as most of the other antibiotics tested appear ineffective; however, chances of development of vancomycinresistant S. aureus are there. In view of this present situation one approach is to opt for newer and more expensive antibiotics like linezolid, dalfopristin-quinopristin and tigecycline for Staphylococcal infections and cefoperazone-sulbactam for Gramnegative infections. Better and a more cost effective approach will be, use of the antibiotics after culture and antibiotic susceptibility testing particularly in ICU 388 Journal of the College of Physicians and Surgeons Pakistan 2010, Vol. 20 (6): 386-390

Hospital acquired infections in a medical intensive care unit patients. The best approach would be to improve and implement optimal infection prevention practices in ICUs of low resource countries and expertise 9 as it is believed that one third of these hospital-acquired infections can be prevented by optimal infection prevention practices. 25 CONCLUSION Bacteria or Candida spp. were isolated from 60.1% samples taken from supposedly infected patients admitted in medical ICU. The most frequent site of infection was the respiratory tract followed by urinary tract. P. aeruginosa, K. pneumoniae and E. coli were the commonest organisms followed by MRSA and S. aureus. The high frequency of HAIs and high bacterial resistance rate in ICU patients indicate the importance to study HAIs and suggest, that more strict measures regarding infection control practices along with prescription of antibiotics according to antibiotic susceptibility testing should be implemented to limit the emergence of antibiotic resistant organisms. Acknowledgement: This study is a part of research project funded by Higher Education Commission of Pakistan, Islamabad. Thanks to my colleagues Mr. Yusuf Rajput, Dr. Umair Mahmood, Dr. Amber Habib, Dr. Abubakr, Dr. Waqas, Mr. Tariq Baig, Mr. Arthur Manzoor, Mr. Muhammad Mushtaq and Mr. Sajjad for their facilitation in this study in their capacity. REFERENCES 1. Richards M, Thursky K, Buising K. Epidemiology, prevalence, and sites of infections in intensive care units. Semin Respir Crit Care Med 2003; 24:3-22. 2. Weinstein RA. Nosocomial infection update. Emerg Infect Dis 1998; 4:416-20. 3. Vincent JL, Bihari DJ, Suter PM, Bruining HA, White J, Nicolas- Chanoin, et al. The prevalence of nosocomial infections in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) Study. EPIC International Advisory Committee. JAMA 1995; 274:639-44. Comment in: JAMA 1996; 275:362. 4. Chen YC, Lin SF, Liu CJ, Jiang DD, Yang PC, Chang SC. Risk factors for ICU mortality in critically ill patients. J Formos Med Assoc 2001; 100:656-61. 5. Shorr AF. Review of studies of the impact on Gram-negative bacterial resistance on outcomes in the intensive care unit. Critical Care Med 2009; 37:1463-9. 6. Girou E, Stephan F, Novara A, Safar M, Fagon JY. Risk factors and outcome of nosocomial infections: results of a matched case-control study of ICU patients. Am J Respir Crit Care Med 1998; 157:1151-8. Comment in: Am J Respir Crit Care Med 1999; 159: 341-2. 7. Richards MJ, Edwards JR, Culver DH, Gaynes RP. Nosocomial infections in combined medical-surgical intensive care units in the United States. Infect Control Hosp Epidemiol 2000; 21:510-5. 8. Kollef MH, Fraser VJ. Antibiotic resistance in the intensive care unit. Ann Intern Med 2001; 134:298-314. Comment in: Ann Intern Med 2002; 136:173; author reply 173. 9. Habibi S, Wig N, Agarwal S, Sharma SK, Lodha R, Pandey RM, et al. Epidemiology of nosocomial infections in medicine intensive care unit at a tertiary care hospital in northern India. Trop Doct 2008; 38:233-5. 10. Gaynes R, Edwards JR. National Nosocomial Infections Surveillance System. Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis 2005; 41:848-54. Epub 2005 Aug 16. Comment in: Clin Infect Dis 2006; 42:577-8; author reply 578. 11. Wahid F, Masood N, Jafri A. Nosocomial pneumonia in mechanically ventilated patients. Pak Armed Forces Med J 2005; 3: 25-8. 12. Rizvi MF, Hasan Y, Memon AR, Abdullah M, Rizvi MF, Saleem S, et al. Pattern of nosocomial infection in two intensive care units of a tertiary care hospital in Karachi. J Coll Physicians Surg Pak 2007; 17:136-9. Comment in: J Coll Physicians Surg Pak 2008; 18:134-5. 13. Albrich WC, Angstwurm M, Bader L, Gartner R. Drug resistance in intensive care units. Infection 1999; 27:S19-23. 14. Fridkin SK, Gaynes RP. Antimicrobial resistance in intensive care units. Clin Chest Med 1999; 20:303-16. 15. Bagshaw SM, Laupland KB. Epidemiology of intensive care unitacquired urinary tract infections. Curr Opin Infect Dis 2006; 19: 67-71. 16. Doshi RK, Patel G, MacKay R, Wallach F. Healthcare-associated infections: epidemiology, prevention and therapy. Mt Sinai J Med 2009; 76:84-94. 17. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial disk susceptibility tests: approved standard. 9th ed. Wayne (PA): Clinical and Laboratory Standards Institute; 2006. 18. Shaikh JM, Devrajani BR, Shah SZ, Akhund T, Ishrat B. Frequency, pattern and aetiology of nosocomial infections in intensive care unit: an experience at a tertiary care hospital. J Ayub Med Coll Abbottabad 2008; 20:37-40. 19. Centers for Disease Control and Prevention. Guideline for prevention of nosocomial pneumonia. MMWR Recomm Rep 1994; 39:1191-236. 20. Izhar M, Khan S, Naqvi A. Anti-microbial resistance among Gram-negative bacteria prevalent in intensive care units. Pak J Surg 2001; 17:23-6. 21. Kohlenberg A, Schwab F, Geffers C, Behnke M, Rüden H, Gastmeier P. Time-trends for Gram-negative and multidrugresistant Gram-positive bacteria associated with nosocomial infections in German intensive care units between 2000 and 2005. Clin Microbiol Infect 2008; 14:93-6. Epub 2007 Nov 22. 22. Fridkin SK, Welbel SF, Weinstein RA. Magnitude and prevention of nosocomial infections in the intensive care unit. Infect Dis Clin North Am 1997; 11:479-96. 23. Monnet DL, Archibald LK, Phillips L, Tenover FC, McGowan JE Jr, Gaynes RP. Antimicrobial use and resistance in eight US hospitals: complexities of analysis and modeling. Intensive care Journal of the College of Physicians and Surgeons Pakistan 2010, Vol. 20 (6): 386-390 389

Naeem Akhtar antimicrobial resistance epidemiology project and national nosocomial infections surveillance system hospitals. Infect Control Hosp Epidemiol 1998; 19:388-94. 24. Lockhart SR, Abramson MA, Beekmann SE, Gallagher G, Riedel S, Diekema DJ, et al. Antimicrobial resistance among Gram-negative bacilli causing infections in intensive care unit patients in the United States between 1993 and 2004. J Clin Microbiol 2007, 45:3352-9. 25. Haley RW, Culver DH, White JW, Morgan WM, Emori TG, Munn VP, et al. The efficacy of infection surveillance and control programs in preventing nosocomial infections in US hospitals. Am J Epidemiol 1985; 121:182-205. 390 Journal of the College of Physicians and Surgeons Pakistan 2010, Vol. 20 (6): 386-390