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Volume 23 |
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Number 1 |
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Published by : PROFESSIONAL MEDICAL PUBLICATIONS |
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ORIGINAL ARTICLE |
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Volume 23 |
January - March 2007 |
Number 1 |
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Resistant gram-negative bacilli and antibiotic
consumption in Zarqa, JordanHussein A Bataineh1, Khalid M Alrashed2
ABSTRACT
Objective: To investigate the prevalence of antibiotic resistance among gram-negative bacteria in relation to antibiotic use in Prince Hashem Hospital (PHH), Jordan.
Materials and Methods: One hundred consecutive gram-negative bacterial isolates from different sites were collected from patients admitted to the ICU at PHH. The susceptibilities of the strains to 12 antibiotics were performed and interpreted. The quantities and the numbers of the patients discharged on antibiotics and the quantities consumed were obtained from the hospital pharmacy records.
Results: The most common isolate was P. aeruginosa (n=21) The most common site of isolation was the respiratory tract (65%), The highest susceptibility was to piperacillin/ tazobactam(78%), and the lowest was to cefuroxime(34%). The aminoglycosides gentamicin and amikacin were active against 71% and 73% of the isolates respectively, Ciprofloxacin was active against 75% of the isolates. The most frequently used antibiotics were the third-generation cephalosporins ceftriaxone and ceftazidime, followed by imipenem and amikacin.
Conclusion: Antibiotic resistance surveillance programs associated with registration of antibiotic consumption are necessary to promote optimal use of antibiotics. Rational prescribing of antibiotics should be encouraged through educational programs, surveillance and audit. Proper infection control measures should be practiced to prevent horizontal transfer of drug-resistant organisms.
Key words: Antibiotic, Resistance, Gram-Negative Bacilli.
Pak J Med Sci January - March 2007 Vol. 23 No.1 59-63
1. Dr. Hussein A Bataineh
2. Dr. Khalid M Alrashed1-2: Prince Hashem Hospital,
P.O. Box: 206,
Aidoun – 2116,
Jordan.Correspondence:
Dr. Hussein A Bataineh,
E-Mail: hussein_azzam@yahoo.com* Received for Publication: March 15, 2006
* Accepted: September 14, 2006
INTRODUCTION
Since the discovery of antimicrobial agents, micro-organisms have developed virtually unlimited resistance to them.
1 Hospitals and particularly intensive care units are an important breeding ground for the development of antibiotic-resistant bacteria. This is the consequence of heavy antibiotic use.In addition, a high-density patient population in frequent contact with health care staff and the attendant risk of cross-infection contributes to the spread of antibiotic-resistant micro-organisms. This in turn increases the morbidity and mortality associated with infections and contributes to rising costs of health care.
2,3MATERIALS AND METHODS
Specimen Collection and Identification of Isolates:
One hundred consecutive gram-negative bacterial isolates from different sites were collected from patients admitted to the ICU at Prince Hashem Hospital Jordan. The clinical significance of the isolates was confirmed by analysis of patients’ records and discussion with the treating clinician. All bacterial strains were identified by their colonial morphology, gram reaction, the oxidized and other biochemical reactions as performed by either API 20E, or API 20NE (bioMerieux, France).
Susceptibility Testing:
The susceptibilities of the strains to 12 antibiotics (co- amoxiclav, cefuroxime, cefotaxime, ceftriaxone, cefta-zidime, aztreonam, piperacillin, piperacillin/tazobactam, imipenem, gentamicin, amikacin, and ciprofloxacin) were performed by determining the minimum inhibitory concentration (MIC), using the E-test (AB BIODISK, Sweden), with E. coli NCTC 10418 and P. aeruginosa NCTC 10662 as controls. The interpretation standards for MICs of the NCCLS were used to determine antibiotic susceptibilities.
4 To detect extended spectrum β-lactamases (ESBL), ceftazidime-resistant strains of E. coli and Klebsiella spp. were further tested against ceftazidime/clavulanic acid. Isolates with a reduction of ceftazidime MIC by >3 two-fold dilutions in the presence of clavulanic acid were considered ESBL producers, and thus resistant to other cephalosporins.Antibiotic Consumption:
The quantities of antibiotics consumed in the ICU during the period of the study were obtained from the hospital pharmacy records and the numbers of the patients discharged were obtained from the hospital records. The estimated days of antibiotic treatment were calculated from the antibiotic daily dose, the total amount consumed and the number of patients who left ICU during the period of study. The antibiotic consumption is expressed as days of treatment per 100 patient discharges.
RESULTS
Bacterial Isolates:
The frequency of the bacterial isolates and their sites of isolation are shown in Table-I. The most common isolates were P. aeruginosa (n=21), Klebsiella spp. (n=20), E. coli (n=13), Enterobacter spp. (n=12), and Stenotrophomonas maltophilia (n=9). The most common sites of isolation were the respiratory tract (65%), urine (14%), wounds (11%) and blood (7%). P. aeruginosa was the most frequent isolate from the respiratory specimens, E. coli was the most from urine and P. mirabilis from wounds.
Susceptibility Patterns:
Antibiotic susceptibilities of the bacterial strains are shown in Table-II. The highest in vitro susceptibility was to piperacillin/tazobactam and ciprofloxacin (78% and 75%), and the lowest was to cefuroxime and coamoxiclav (34%, 20%). The susceptibility of the isolates to cephalosporins ranged from 71% for ceftazidime to 34% for cefuroxime. Only 55% of strains were susceptible to ceftriaxone and 52% to cefotaxime. Ceftazidime showed good activity against P. aeruginosa, and P. mirabilis, inhibiting 81% and 100%, respectively. Resistance to cephalosporins was encountered with Enterobacter spp. and Acinetobacter spp. Aztreonam showed similar activity to ceftazidime against all strains. The aminoglycosides gentamicin and amikacin were active against 71% and 73% of the isolates, respectively. Four strains, two Klebsiella spp., one P. aeruginosa, and one S. maltophilia were resistant to amikacin but sensitive to gentamicin. Imipenem inhibited 69% of the isolates, but only 11% of S. maltophilia. Two of the six P. mirabilis isolates were resistant to imipenem but sensitive to cefuroxime and co-amoxiclav. Ciprofloxacin was active against 75% of the isolates but only 50% of Enterobacter spp.
Rates of Antibiotic Consumption:
The consumption of antibiotics in the ICU is shown in Table-III. The total amount of antibiotics consumed was equivalent to 916 estimated days of treatment/100 hospital discharges. The most frequently used antibiotics were the third-generation cephalosporins ceftriaxone and ceftazidime, followed by imipenem and amikacin. Among the least consumed were co-amoxiclav and piperacillin.
DISCUSSION
During the study period, every 100 patients treated in the ICU received an average of 916 days of antibiotic treatment, mostly third- generation cephalosporins, imipenem, ciprofloxacin and amikacin which was 50% higher than the consumption in Oman in 1996.
5As for the individual antibiotics, there was a four-fold rise in the consumption of ciprofloxacin and three-fold rise in the consumption of imipenem and ceftazidime. Given this substantial use of antibiotics, it is not surprising to note the change in the microbial ecology, with predominance of multiresistant strains of P. aeruginosa, Klebsiella spp., Enterobacter spp. and S. maltophilia. It is well documented that the indiscriminate use of antibiotics has led to the selection and dissemination of antibiotic-resistant organisms.
6Several authors have reported the association of resistance to b -lactam antibiotics with prior use of third-generation cephalosporins.
7,8 A common mechanism of cephalosporin resistance among Klebsiella spp. and E. coli is the production of ESBL.9 In this study, three Klebsiella spp. (15%) and two E. coli (15%) were resistant to third-generation cephalosporins and aztreonam, suggesting production of Extended Spectrum b -Lactamases (ESBL) by these strains. This was confirmed by their susceptibility to ceftazclav. However, with this test alone inhibitor-resistant TEM (IRT) mutants may not be detected. Nevertheless, we believe that IRT mutants are probably prevalent in our hospitals, since 62% of E. coli in this study were resistant to co-amoxiclav, suggesting the possibility of IRT production. IRT-producing mutants have been reported in both general practice and hospitals.10,11Nosocomial outbreaks of Klebsiella spp. resistant to the third-generation cephalosporins due to the production of ESBL have been reported worldwide.
9 Although there was an increase in the consumption of cephalosporins in 1998 when this study was conducted, the incidence of probable ESBL producers was much lower than that in 1996,5 a fact which we are unable to explain. Carbapenems, being strong inducers of class C b -lactamases, could also have contributed to the resistance to b -lactams, including third-generation cephalosporins. Furthermore, it has been shown that treatment with imipenem, but not with other b -lactam drugs, is a major risk factor for the development of imipenem-resistant P. aeruginosa in hospitalized patients.12 Imipenem resistance in this study was high, particularly among P. aeruginosa and Enterobacter spp., compared to the study done in 1996, when fewer carbapenems were used.5 Furthermore, patients receiving carbapenems, particularly those on mechanical ventilation, are at an increased risk of colonization or infection with class B metallo-enzyme producers such as S. maltophilia.13,14 Indeed, with the increased use of carbapenems, more strains of S. maltophilia were isolated compared to the earlier study. About 70% of these strains were resistant to imipenem, and most were isolated from the respiratory tract of mechanically ventilated patients.Overuse of carbapenems in our ICUs has also provoked a unique type of resistance among P. mirabilis. Two strains (33%) of P. mirabilis were resistant to imipenem but sensitive to cefuroxime and co-amoxiclav. Medeiros (1997) attributed this resistance to an altered penicillin-binding protein to which imipenem cannot bind, but other b-lactams can.
15Resistance to gentamicin and amikacin in our study was relatively high. Four isolates were resistant to amikacin but sensitive to gentamicin. This is probably due to selective pressure associated with the high consumption of amikacin in our ICU. This phenomenon has been reported in similar situations, due to aminoglycoside-modifying enzyme N-acetyl transferase (ACC6’-[I]) that hydrolyses amikacin, tobramycin, and netilmicin, but not gentamicin.
16 There was an alarming increase in the level of resistance to ciprofloxacin in our hospital, as only 75% of the isolates were inhibited, compared to 94% in 1996.5 This is probably a result of the increased consumption of ciprofloxacin in 1998, leading to the selection of resistant mutants. The emergence of resistance to fluoroquinolones in virtually all species of bacteria was recognized after the introduction of these compounds for clinical use.17 Now increase in the levels of resistance to the fluoroquinolones among nosocomial isolates, like P. aeruginosa, Serratia spp. and Klebsiella spp., has been reported worldwide.17The gravity of the problem of antimicrobial resistance continues to receive global attention, as evidenced by the pan-European meeting in Copenhagen.
18 Given this escalation in resistance and the overwhelming evidence of overuse of antibiotics, the pragmatic and essential approach to control antibiotic resistance is control of antibiotic use. Apparently, there are reasons for optimism, as studies in various centers showed rapid reversal of resistance.19-21 National guidelines on this topic and good diagnostic and therapeutic protocols are important. Continued surveillance of prevalent strains and their resistance patterns is fundamental as a means of establishing the significance of resistance in clinical infection, and in the determination of hospital-prescribing policies. Antibiotic resistance surveillance programs associated with registration of antibiotic consumption are necessary to promote optimal use of antibiotics. Rational prescribing of antibiotics should be encouraged through educational programs, surveillance and audit. Proper infection control measures must also be practiced to prevent horizontal transfer of drug-resistant organisms.REFERENCES
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3. Hanberger H, Lennat E. High frequency of antibiotic resistance among gram-negative isolates in ICUs at 10 Swedish hospitals. Clin Microb Infect 1997;3:209-15.
4. National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial disk susceptibility tests (M7-A4). Vol. 17, No. 1997.
5. ElHag KM, Reed M, Allwaty HM. The prevalence of antibiotic resistance among gram-negative bacilli from ICU in Oman. Saudi Med J 1999;20:373-7.
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8. Rello R, Ausina V, Rilant M, Castella J, Prats G. Impact of previous antimicrobial therapy on the aetiology and outcome of ventilation associated pneumonia. Chest 1993;104:1230-5.
9. Sirot D. Extended spectrum plasmid mediated b -lactamases. J antimicrob Chemother 1995;36(Suppl A):S19-34.
10. Chaibi EB, Sirot D, Paul G, Labia R. Inhibitor resistant TEM b-lactamase: phenotypic, genetic and biochemical characteristics. J antimicrob Chemother 1999;43:447-58.
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16. Miller GH, Stabatelli RS, Hars RS. The most frequent aminoglycoside resistance mechanisms. Changes with time and geographic area, a reflection of aminoglycoside usage patterns. Clin Infect Dis 1997;24 (suppl 1):S46-S62.
17. Acar JF, Goldstein FW. Trends in bacterial resistance to fluoroquinolones. Clin Infects Dis 1997;24:S67-S73.
18. The Copenhagen recommendations. Report from the invitational European Union Conference on the microbial threat. Copenhagen, Denmark, September 1998.
19. Ridley M, Lynn R, Barrie D, Stead KC. Antibiotic resistant Staphylococcus aureus and hospital antibiotic policies. Lancet 1970; 230-1.
20. Ballow CH, Schentag JJ. Trends in antibiotic utilization and bacterial resistance. Diagn Microb Infect Dis 1992; 15(Suppl):27S-42S.
21. Meyer KS, Urban C, Eagan JA, Berger BJ, Rahal JJ. Nosocomial outbreak of Klebsiella: infection resistant to late generation cephalosporins. Ann Intern Med 1993;119:353-8.
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