Antimicrobial Resistance Pattern and Spectrum of Multiple-drug-resistant Enterobacteriaceae in Iranian Hospitalized Patients with Cancer
Hossein Fazeli, Sharareh Moghim, Donya Zare
Department of Microbiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
|Date of Web Publication||24-Apr-2018|
Ms. Donya Zare
Department of Microbiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan
Source of Support: None, Conflict of Interest: None
Background: Nosocomial infections are one of the most leading causes of morbidity and mortality in patients with cancer. The emergence of multiple-drug-resistant (MDR) strains of Gram-negative bacteria causing nosocomial infection has become a serious concern in cancer patients. Therefore, the present study aimed to determine the spectrum and antibiotic resistance pattern of Gram-negative bacteria related nosocomial infections among Iranian cancer patients. Materials and Methods: This descriptive cross-sectional study was conducted during the 6 months from December 2015 to May 2016 in two tertiary care centers located in Isfahan and Arak Province. Gram-negative bacteria obtained from different clinical specimens from hospitalized patients with cancer and were identified using standard microbiological methods. Antibiotic susceptibility pattern was determined by the disk diffusion method according to the Clinical and Laboratory Standards Institute (CLSI) recommendation. Results: Of totally 259 culture positive cases, Escherichia coli showed the highest isolation rate (60.6%) followed by Klebsiella pneumoniae (26.6%) and Proteus spp (11.2%). The rate of MDR isolates were 91.5% (237/259). Overall, the most frequent source of bacterial isolation was urinary tract infection (65.6%) followed by skin and soft-tissue infection (23.6%). The antibiotic susceptibility results showed meropenem (MEN) and ceftazidime as the most effective antibiotics for E. coli, K. pneumoniae, and Proteus spp. isolates. Moreover, MEN was the most effective antibiotic against MDR isolates. Conclusion: The study findings showed a significant distribution of MDR Gram-negative bacteria which may increase the burden of healthcare-associated infections in cancer patients. Although, carbapenem can be considered as effective agents toward MDR strains for empirical antibiotic therapy in our region.
Keywords: Antibiotic resistance, cancer, enterobacteriaceae, nosocomial infection
|How to cite this article:|
Fazeli H, Moghim S, Zare D. Antimicrobial Resistance Pattern and Spectrum of Multiple-drug-resistant Enterobacteriaceae in Iranian Hospitalized Patients with Cancer. Adv Biomed Res 2018;7:69
|How to cite this URL:|
Fazeli H, Moghim S, Zare D. Antimicrobial Resistance Pattern and Spectrum of Multiple-drug-resistant Enterobacteriaceae in Iranian Hospitalized Patients with Cancer. Adv Biomed Res [serial online] 2018 [cited 2019 Feb 21];7:69. Available from: http://www.advbiores.net/text.asp?2018/7/1/69/230870
| Introduction|| |
Cancer is a significant cause of death worldwide, and more than half of them occur in developing countries. The most common causes of cancer death are lung, liver, colorectal, stomach, breast cancer, and leukemia. The new advances in treatment options increased survival rates of cancer patients in the past decades. However, severe immunosuppression as an adverse consequence of these treatment strategies increases the risk of opportunistic infections.
Nosocomial infections are one of the most serious complications and the leading cause of morbidity and mortality in patients with cancer. There are several risk factors for acquisition of nosocomial infections such as neutropenia, stem cell transplantation, long-term catheterization, and the extensive use of medical devices such as stents, shunts, and central venous catheters., The most common sites of infections are bloodstream infections (BSIs), respiratory tract infections, urinary tract infections (UTIs), and surgical site infections., A wide range of bacteria has been reported as a cause of nosocomial infections that among them, Gram-negative bacteria, particularly Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae are the most prevalent. The reported prevalence of these organisms estimated more than 30% of hospital-acquired infections and 70% of infections in the intensive care unit.
The emergence of multiple-drug-resistant (MDR) strains of Gram-negative bacteria causing nosocomial infection has become a serious concern, especially in cancer patients. In recent years, the majority of conducted studies in cancer patients have only focused on BSIs, and there is no study looking at the overall prevalence of Gram-negative bacteria related infections among Iranian cancer patients. Therefore, the present study aimed to determine the spectrum and antibiotic resistance pattern of Gram-negative bacteria related nosocomial infections among Iranian cancer patients. This information can help clinicians to choose effective empirical therapies and provide good epidemiological profiles to compare our situation with others.
| Materials and Methods|| |
This descriptive cross-sectional study was conducted during the 6 months from December 2015 to May 2016 in two tertiary care centers located in Isfahan and Arak Province (located in the central part of Iran). These centers providing treatment for cancer patients with radiotherapy, chemotherapy, and hormonal therapy. All hospitalized cancer patients undergoing anti-cancer therapy. Demographic characteristics consisted of demographic data including age, sex, admission date, hospitalization duration, ward, type of cancer, and sites of infections were collected from the patients. This study was in accordance with the declaration of Helsinki and approved by the regional Ethics Committee. We only used medical records, and the details were kept strictly confidential.
Sampling and isolation
Nonduplicate clinical specimens were collected from urine, wound, blood, sputum, and stool samples from cancer patients. All clinical specimens were cultured on blood agar and MacConkey agar and incubated aerobically at 37°C for 24 h. Standard microbiological methods consist of reaction with Triple Sugar Iron agar, Simmons' citrate agar, Christensen's urea agar, Indole test, Methyl red, and Voges–Proskauer tests were followed for the isolation and identification of Gram-negative bacteria.
Antimicrobial susceptibility testing
Antibiotic susceptibility pattern was determined by the disk diffusion method on Mueller– Hinton agar (Himedia, India) according to the CLSI recommendation. The used antibiotic disks were imipenem (10 μg), meropenem (MEN) (10 μg), cefepime (FEP) (30 μg), ceftazidime (CAZ) (30 μg), cefotaxime (CTX) (30 μg), co-trimoxazole (SXT) (75 μg), gentamicin (GM) (10 μg), amikacin (AN) (30 μg), ciprofloxacin (CIP) (5 μg) ofloxacin (OFX) (5 μg), and nitrofurantoin (FM) (300 μg) disks (Padtan Teb, Iran). Antimicrobial susceptibility of Salmonella More Details and Shigella isolates was determined toward ampicillin (10 μg), CTX (30 μg), FEP (30 μg), SXT (75 μ), CIP (5 μg), and nalidixic acid (30 μg). Escherichia More Details coli ATCC 25922 was used as a control strain for susceptibility testing. MDR was defined by nonsusceptible to ≥1 agent in ≥3 antimicrobial categories as previously described.
Analyses were performed using SPSS ™ software, version 21.0 (IBM Corp., New York, USA). The results are presented as descriptive statistics in terms of relative frequency. Values were expressed as the mean ± standard deviation (SD) (continuous variables) or percentages of the group (categorical variables).
| Results|| |
Totally 259 nonduplicates Gram-negative bacteria collected from clinical specimens at two studied hospitals in Isfahan and Arak, Iran. Out of the 259 positive cultures, 142 (54.8%) belonged to females and 117 (45.2%) were from males. The mean age of the patients was 48.5 ± 18.9 (mean ± SD) years, and the age range was from 8 to 89 years. The most prevalent cancer type among patient was blood cancer (35.1%) followed by prostate cancer (11.6%). Of culture-positive cases, E. coli showed the highest isolation rate (60.6%) followed by Klebsiella pneumoniae (26.6%) and Proteus spp.(11.2%). Overall, the rate of MDR isolates were 91.5% (237/259). The full results of bacterial isolation and MDR rates according to the type of cancer are presented in [Table 1]. Overall, the most frequent source of bacterial isolation was from UTIs (65.6%) followed by skin and soft tissue infections (SSTIs) (23.6%) [Table 2]. The majority of patients were hospitalized in ICUs (64.5%) followed by internal wards (33.6%), and surgery wards (1.9%).
|Table 1: Distribution of isolated bacteria in according to type of cancera|
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|Table 2: Distribution of Gram-negative isolates in according to sources of infectionsa|
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The antibiotic susceptibility results showed MEN and CAZ as the most effective antibiotics toward E. coli, K. pneumoniae and Proteus spp. isolates. The results of antibiotic susceptibility pattern of pathogens obtained from cancer patients are shown in [Table 3]. All the recovered Salmonella isolates were susceptible to ampicillin, CTX, FEP, CIP, and trimethoprim/sulfamethoxazole and only resistant to nalidixic acid. Moreover, Shigella isolates were susceptible to FEP, CIP, and nalidixic acid. For 237 MDR isolates in this study, the highest antibiotic sensitivity was toward MEN and CAZ with 67.9% and 59.5%, respectively.
|Table 3: The antibiotic susceptibility pattern of pathogens isolated from cancer patients|
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| Discussion|| |
The management of nosocomial infections in patients with cancer is a priority of public health due to its rapid onset and high level of morbidity and mortality. Due to diverse nature of nosocomial infections etiology and antibiotic resistance patterns in periodic intervals, routine surveillance is needed to prevent the occurrence and transmission of nosocomial pathogens., In the present study, we have analyzed the distribution and antibiotic resistance of nosocomial pathogens isolated from Iranian cancer patients.
In the present study, 65.6% of cancer patients developed UTIs and 23.6% SSTIs. This is consistent with other studies which reported UTIs and SSTIs as the common sites of infections in cancer patients.,, We found that E. coli and K. pneumoniae were the most frequent Gram-negative bacteria isolated from cancer patients. Despite some reports inconsistent with our findings,,,, still, there is controversy about the prevalence of common etiology of nosocomial infections in patients with cancer. However, some reasons may explain the observed discrepancies in etiology of nosocomial infections. The variation in the prevalence of Gram-negative bacteria may arise from the differences in sample size, the source of infections, type of cancer, and geographical distribution.
Regarding antimicrobial susceptibility among Gram-negative bacteria, with some variation closest to our findings Eslami Nejad et al. from Kerman and Abdollahi et al. from Tehran introduced carbapenem and third-generation cephalosporins as the most effective antibiotics against pathogens recovered from Iranian cancer patients., Moreover, despite the comparable antibiotic resistance results of our study with other foreign studies, antibiotic susceptibility patterns have a variable nature according to the geographical area.,,,
In our results, the estimated rate of MDR isolates was remarkable (91.5%). Our estimated MDR rates were significantly higher compared to those that were previously reported for E. coli (37%), and K. pneumoniae (33%) by Eslami Nejad et al. from Kerman (Southeast Iran, 2010) among cancer patients who developed BSIs. Besides the study of Eslami Nejad et al. as the only specific report on MDR rate among Iranian cancer patients, there are several recent studies that showed high rates of MDR pathogens in Iranian hospitals.,, In recent years, the emergence of MDR strains is growing problem in Iranian health-care centers, especially extended-spectrum beta-lactamases and carbapenem producing strains of enterobacteriaceae., The study findings showed the promising effect of carbapenem for MDR isolates and can be recommended for treatment of related infections in patients with cancer. Despite reports that are indicating to increasing trend of carbapenem resistance among enterobacteriaceae our findings emphasize the effectiveness of these agents.
As the main limitation of the present study, we did not explore the microbial spectrum of Gram-positive bacteria as one of the main causes of nosocomial infections in cancer patients.,
The continuous evolution of pathogens in hospital environments necessitates continuous updating of local data on bacterial etiology and antimicrobial susceptibility to improve the outcome of nosocomial infections.
| Conclusion|| |
The study findings showed a significant distribution of MDR Gram-negative bacteria which may increase the burden of healthcare-associated infections in cancer patients. Although, carbapenem can be considered as effective agents toward MDR strains for empirical antibiotic therapy in our region. Moreover, mechanisms of resistance should also be investigated for better characterization of antibiotic-resistant Gram-negative isolates.
| Acknowledgment|| |
We are thankful to all Members of Department of Microbiology, School of Medicine, Isfahan University of Medical Sciences. This was an original research paper from master's thesis. This study was funded in part by a grant from the Isfahan University of Medical Sciences, (grant no; 395176).
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D, et al.
Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, et al.
Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin 2016;66:271-89.
O'Connor A, Qasim A, O'Moráin CA. The long-term risk of continuous immunosuppression using thioguanides in inflammatory bowel disease. Ther Adv Chronic Dis 2010;1:7-16.
Kamboj M, Sepkowitz KA. Nosocomial infections in patients with cancer. Lancet Oncol 2009;10:589-97.
Custovic A, Smajlovic J, Hadzic S, Ahmetagic S, Tihic N, Hadzagic H, et al.
Epidemiological surveillance of bacterial nosocomial infections in the surgical Intensive Care Unit. Mater Sociomed 2014;26:7-11.
Cornejo-Juárez P, Vilar-Compte D, Pérez-Jiménez C, Ñamendys-Silva SA, Sandoval-Hernández S, Volkow-Fernández P, et al.
The impact of hospital-acquired infections with multidrug-resistant bacteria in an oncology Intensive Care Unit. Int J Infect Dis 2015;31:31-4.
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing. 26th
Informational Supplement. Wayne, Pennsylvania: Clinical and Laboratory Standards Institute; 2016.
Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al.
Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012;18:268-81.
Struelens MJ. The epidemiology of antimicrobial resistance in hospital acquired infections: Problems and possible solutions. BMJ 1998;317:652-4.
Abdollahi A, Hakimi F, Doomanlou M, Azadegan A. Microbial and antibiotic susceptibility profile among clinical samples of patients with acute leukemia. Int J Hematol Oncol Stem Cell Res 2016;10:61-9.
Ashour HM, El-Sharif A. Species distribution and antimicrobial susceptibility of gram-negative aerobic bacteria in hospitalized cancer patients. J Transl Med 2009;7:14.
Nurain AM, Bilal NE, Ibrahim ME. The frequency and antimicrobial resistance patterns of nosocomial pathogens recovered from cancer patients and hospital environments. Asian Pac J Trop Biomed 2015;5:1055-9.
Nesher L, Rolston KV. The current spectrum of infection in cancer patients with chemotherapy related neutropenia. Infection 2014;42:5-13.
Bhat V, Gupta S, Kelkar R, Biswas S, Khattry N, Moiyadi A, et al.
Bacteriological profile and antibiotic susceptibility patterns of clinical isolates in a tertiary care cancer center. Indian J Med Paediatr Oncol 2016;37:20-4.
] [Full text]
Lanoix JP, Pluquet E, Lescure FX, Bentayeb H, Lecuyer E, Boutemy M, et al.
Bacterial infection profiles in lung cancer patients with febrile neutropenia. BMC Infect Dis 2011;11:183.
Eslami Nejad Z, Ghafouri E, Farahmandi-Nia Z, Kalantari B, Saffari F. Isolation, identification, and profile of antibiotic resistance of bacteria in patients with cancer. Iran J Med Sci 2015; 35: 109-15.
Trecarichi EM, Pagano L, Candoni A, Pastore D, Cattaneo C, Fanci R, et al.
Current epidemiology and antimicrobial resistance data for bacterial bloodstream infections in patients with hematologic malignancies: An Italian multicentre prospective survey. Clin Microbiol Infect 2015;21:337-43.
Prabhash K, Medhekar A, Ghadyalpatil N, Noronha V, Biswas S, Kurkure P, et al.
Blood stream infections in cancer patients: A single center experience of isolates and sensitivity pattern. Indian J Cancer 2010;47:184-8.
] [Full text]
Moini AS, Soltani B, Taghavi Ardakani A, Moravveji A, Erami M, Haji Rezaei M, et al.
Multidrug-resistant Escherichia coli
and Klebsiella pneumoniae
isolated from patients in Kashan, Iran. Jundishapur J Microbiol 2015;8:e27517.
Dehbanipour R, Rastaghi S, Sedighi M, Maleki N, Faghri J. High prevalence of multidrug-resistance uropathogenic Escherichia coli
strains, Isfahan, Iran. J Nat Sci Biol Med 2016;7:22-6.
Malekzadegan Y, Hadadi M, Ebrahim-Saraie HS, Heidari H, Motamedifar M. Antimicrobial resistance pattern and frequency of multiple-drug resistant Enterobacter
spp. At a tertiary care hospital in Southwest of Iran. J Krishna Inst Med Sci Univ 2017;6:33-9.
Leylabadlo HE, Pourlak T, Bialvaei AZ, Aghazadeh M, Asgharzadeh M, Kafil HS, et al.
Extended-spectrum beta-lactamase producing gram negative bacteria In Iran: A review. Afr J Infect Dis 2017;11:39-53.
Zahedi Bialvaei A, Samadi Kafil H, Ebrahimzadeh Leylabadlo H, Asgharzadeh M, Aghazadeh M. Dissemination of carbapenemases producing gram negative bacteria in the Middle East. Iran J Microbiol 2015;7:226-46.
Ashour HM, el-Sharif A. Microbial spectrum and antibiotic susceptibility profile of gram-positive aerobic bacteria isolated from cancer patients. J Clin Oncol 2007;25:5763-9.
[Table 1], [Table 2], [Table 3]