|Year : 2014 | Volume
| Issue : 4 | Page : 560-562
Efficacy of anti-pseudomonal antibiotics: Need to reconsider the empirical use of cefepime
A Kotwal, D Biswas, B Kakati, B Thakuria, N Bhardwaj
Department of Microbiology, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Jolly Grant, Dehradun 248 140, India
|Date of Web Publication||5-Dec-2014|
Department of Microbiology, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Jolly Grant, Dehradun 248 140
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Kotwal A, Biswas D, Kakati B, Thakuria B, Bhardwaj N. Efficacy of anti-pseudomonal antibiotics: Need to reconsider the empirical use of cefepime. Indian J Med Res 2014;140:560-2
|How to cite this URL:|
Kotwal A, Biswas D, Kakati B, Thakuria B, Bhardwaj N. Efficacy of anti-pseudomonal antibiotics: Need to reconsider the empirical use of cefepime. Indian J Med Res [serial online] 2014 [cited 2021 May 6];140:560-2. Available from: https://www.ijmr.org.in/text.asp?2014/140/4/560/146272
Pseudomonas aeruginosa accounts for approximately 10 per cent of all nosocomial infections and is associated with widespread antibiotic resistance ,, . Inappropriate selection of antibiotics leads to increased mortality and, hence, management of this infection needs to be tailored according to local antibiogram patterns , . Cefepime is one of the few antibiotics reported to have consistent anti-pseudomonal activity, though reports on cefepime resistance are rising ,, . We, therefore, analyzed the susceptibility pattern of P. aeruginosa to cefepime and compared the same with other anti-pseudomonal antibiotics.
This prospective study was performed in the department of Microbiology, Himalayan Institute of Medical Sciences, Dehradun, Uttrakhand, India during March 2010 to February 2012. The study protocol was approved by the institutional ethics committee. All consecutive patients with positive P. aeruginosa culture were included in the study. The calculation of sample size was based on presumptive prevalence of 40-50 per cent resistance among the recovered P. aeruginosa isolates to third-generation cephalosporins ,, . The optimum sample size calculated was between 600 and 617. Antimicrobial sensitivity, with commercial discs Himedia, India was tested against piperacilin, piperacillin-tazobactam, ceftazidime, cefepime, ciprofloxacin, gentamicin, amikacin and imepenem by Kirby-Bauer method, following the recommendations of Clinical and Laboratory Standards Institute (CLSI)  . ATCC 25873 strain of P. aeruginosa was used as control and interpretation of antimicrobial sensitivity was done according to interpretive criteria published in CLSI guidelines.
Proportions of sensitive isolates recovered from out-patients and in-patients were compared using Chi-square test. Sensitivity to cefepime vis-a-vis other antibiotics was compared using Chi-square test and Fisher's exact test, wherever appropriate. SPSS version 17.0 (Chicago: SPSS Inc. USA) was used and p <0.05 was considered significant.
A total of 618 consecutive isolates of P. aeruginosa, recovered from as many patients, were included. The median (5 th - 95 th percentile) age of the patients was 68 (range 45-88) years. The isolates were recovered from a variety of specimens, including pus (n= 249), urine (n=123), endotracheal secretions (n=84), throat swab (n=12), sputum (n=31), trans-tracheal secretions (n=49), bronchoalveolar lavage fluid (n=27), double lumen jugular catheter (n=24) and eye discharge (n=19). Approximately two-thirds of the isolates were recovered from in-patients (n= 408; 66%).
We observed sensitivity to piperacillin-tazobactam in >90 per cent isolates (n= 574, 92.9%), followed by piperacillin (n=551, 89.1%) and imipenem (n=446, 72.1%). Moderate sensitivity, ranging from 40.7 to 60 per cent, was observed for amikacin and the third-generation cephalosporins. However, cefepime demonstrated poorer anti-pseudomonal activity compared to each of the third-generation cephalosporins ([Table 1]). Considering the isolates from out-patients and in-patients to be representatives of community-acquired and nosocomial isolates respectively, we observed that a significantly higher proportion of nosocomial isolates were resistant to ceftriaxone (48.93%) and cefoperazone (43.4%). Resistance was significantly higher (P<0.001) among community-acquired isolates for majority of the antibiotics ([Table 1]).
|Table 1: Susceptibility pattern of P. aeruginosa isolates to anti-pseudomonal antibiotics from OPD (Out patient department) and IPD (Inpatient department) |
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A significantly higher proportion of isolates was resistant to cefepime and sensitive to other antibiotics. Piperacillin-tazobactam, piperacillin and imipenem were most effective against cefepime-resistant isolates ([Table 2]). Resistance to all cephalosporins was seen in 74 (11.9%) isolates, of which 44 (59.5%), 61 (82.4%) and 58 (78.3%) were sensitive to piperacillin, piperacillin-tazobactam and imipenem, respectively, thereby further validating the anti-pseudomonal efficacy of piperacillin-tazobactam.
|Table 2: Comparison of the anti-pseudomonal activity of cefepime vis-à-vis other antibiotics |
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An alarming level of resistance was observed to almost all anti-pseudomonal antibiotics with the community-acquired P. aeruginosa isolates demonstrating higher resistance compared to hospital isolates. We had earlier reported antibiotic resistance in a relatively higher proportion of P. aeruginosa isolates recovered from this region , . In this study a higher percentage of antibiotic resistance was seen among community-acquired isolates, though the mechanism underlying this phenomenon is unclear. The reason could be an indiscriminate use of antibiotics in the local community.
The considerably higher resistance to cefepime, compared than to the older third-generation cephalosporins was also unexpected. Compared to third-generation cephalosporins, the fourth-generation cephalosporins are poor inducers of, and relatively resistant to type I chromosomally-encoded and some plasmid-mediated β-lactamases and extended-spectrum β-lactamases  . Consequently these are traditionally described to have an extended antibacterial spectrum and have been recommended for empirical treatment of serious infections in hospitalized patients, in whom Gram-positive microorganisms, Enterobacteriaceae, and Pseudomonas are potential pathogens , . Furthermore, cefepime has been reported to have comparable activity to ceftazidime for P. aeruginosa . Cefepime is also recommended as the drug of choice in febrile neutropenic patients in whom Pseudomonas is a predominant pathogen  . Similar studies need to be done in other parts of the country to assess the actual situation. Further studies should be conducted to elucidate the predominant mechanisms of resistance to β-lactam antibiotics among such isolates. These mechanisms might hint at novel therapeutic targets for the better management of infections due to multi-drug resistant strains of Pseudomonas.
| Acknowledgment|| |
This study was supported by partial funding from Indian Council of Medical Research (ICMR), New Delhi.
| References|| |
Gaynes R, Edwards JR. Overview of nosocomial infections caused by g0 ram-negative bacilli. Clin Infect Dis
Fluit AC, Jones ME, Schmitz FJ, Acar J, Gupta R, Verhoef J. Antimicrobial susceptibility and frequency of occurrence of clinical blood isolates in Europe from the SENTRY antimicrobial surveillance program, 1997 and 1998. Clin Infect Dis
Streit JM, Jones RN, Sader HS, Fritsche TR. Assessment of pathogen occurrences and resistance profiles among infected patients in the intensive care unit: report from the SENTRY Antimicrobial Surveillance Program (North America, 2001). Int J Antimicrob Agents
Micek ST, Lloyd AE, Ritchie DJ, Reichley RM, Fraser VJ, Kollef MH. Pseudomonas aeruginosa
bloodstream infection: importance of appropriate initial antimicrobial treatment. Antimicrob Agents Chemother
Vidal F, Mensa J, Almela M, Martínez JA, Marco F, Casals C, et al
. Epidemiology and outcome of Pseudomonas aeruginosa
bacteremia, with special emphasis on the influence of antibiotic treatment. Analysis of 189 episodes. Arch Intern Med
Sader HS, Fritsche TR, Jones RN. Potency and spectrum trends for cefepime tested against 65,746 clinical bacterial isolates collected in North American medical centers: results from the SENTRY Antimicrobial Surveillance Program (1998-2003). Diagn Microbiol Infect Dis
Croughs PD, Li B, Hoogkamp-Korstanje JA, Stobberingh E. Thirteen years of antibiotic susceptibility surveillance of Pseudomonas aeruginosa
from intensive care units and urology services in the Netherlands. Eur J Clin Microbiol Infect Dis
Robinson CA, Kuhn RJ, Craigmyle J, Anstead MI, Kanga JE. Susceptibility of p0 seudomonas aeruginosa
to cefepime versus ceftazidime in patients with cystic fibrosis. Pharmacotherapy
Sarkar B, Biswas D, Prasad R, Sharma JP. A clinic-microbiological study on the importance of p0 seudomonas
in nosocomially infected ICU patients, with special reference to metallo beta1-lactamase production. Indian J Pathol Microbiol
Sivanmaliappan TS, Sevanan M. Antimicrobial susceptibility patterns of Pseudomonas aeruginosa
from diabetes patients with foot ulcers. Int J Microbiol
Goswami NN, Trivedi HR, Goswami AP, Patel TK, Tripathi CB. Antibiotic sensitivity profile of bacterial pathogens in postoperative wound infections at a tertiary care hospital in Gujarat, India. J Pharmacol Pharmacother
CLSI. Performance standards for antimicrobial susceptibility testing
; Seventeenth informational supplement. CLSI Document M100- S17. Wayne, PA: Clinical and Laboratory Standards Institute; 2007.
Arya M, Prasad R, Arya PK, Gupta P, Biswas D. Antibiotic susceptibility of Pseudomonas aeruginosa isolates in Uttaranchal- a Hospital based study. Indian Med Gazette
Petri WA. Antimicrobial agents: Penicillins, cephalosporins, and other β-lactam antibiotics. In: Hardman JG, Limbird LE, Goodman Gilman A, editors. Goodman & Gilman's the pharmacological basis of therapeutics
, 10 th
ed. New York: McGraw-Hill; 2001. p. 1189-218.
Tamar F, Kasper DL. Approach to the acutely Ill infected febrile patient. In: Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J, editors. Harrison's principles of internal medicine
, vol. I, 18 th
ed. New York: McGraw-Hill; 2008. p. 1023-30.
[Table 1], [Table 2]