|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 25, No 36 (December 20), 2007: pp. 5763-5769 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.14.0947 Microbial Spectrum and Antibiotic Susceptibility Profile of Gram-Positive Aerobic Bacteria Isolated From Cancer Patients
From the Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo; and the Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Al-Azhar Egypt Address reprint requests to Hossam M. Ashour, PhD, Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Kasr El-Aini St, Cairo, Egypt 11562; e-mail: hossamking{at}mailcity.com
Purpose Cancer patients are particularly susceptible to nosocomial infections because of their compromised immune system, and because of the nature of treatment practices they experience. Recently, a shift of the microbial spectrum of cancer patients from Gram-negative to Gram-positive has been demonstrated. This study analyzed the distribution and the antimicrobial resistance of Gram-positive bacteria isolated from cancer patients in Egypt. Patients and Methods We examined the microbial spectrum of Gram-positive bacteria in patients with hematologic malignancies and solid tumors. In addition, we also studied the antimicrobial resistance of pathogens accounting for the majority of Gram-positive infections in these cancer patients.
Results Most of Gram-positive isolates from urinary tract (100%), respiratory tract (89.7%), and bloodstream infections (BSIs; 65.5%) were obtained from leukemic patients. All Gram-positive isolates from skin infections were isolated from solid-tumor patients. In both leukemic and solid-tumor patients, Gram-positive bacteria causing nosocomial BSI were mainly Coagulase-negative staphylococcus (CNS) and S aureus, whereas Gram-positive bacteria causing nosocomial RTI were mainly Conclusion This is the first study to report the emergence of vancomycin- and linezolid-resistant S aureus in Egypt. Newer generation quinolones (moxifloxacin and gatifloxacin) were more active than older quinolones (ciprofloxacin and ofloxacin) against S aureus and CNS, suggesting the use of newer generation quinolones in the prophylaxis of cancer patients.
Nosocomial infections are infections acquired at the hospital, as evidenced by an incubation period of the infection that is less than the interval between admission and onset of symptoms. Severe nosocomial infections contribute significantly to the morbidity and mortality rates in hospitals.1 Because of the large number of patients who acquire nosocomial infections annually, significant financial costs result.1,2 Cancer patients are more susceptible to infections associated with health care because of their compromised immune system, use of invasive technologies, and their being subjected to surgical operations and chemotherapy.3 New tools, aggressive practices, and technologies for the treatment of cancer patients can facilitate the onset of infections by microorganisms that were once considered as nonpathogenic or saprophytic.4 Institutions that provide care for cancer patients are expected to have higher rates of nosocomial infections than general care hospitals.5 In most hospitals nowadays, there is a shift of the microbial spectrum of cancer patients from Gram-negative to Gram-positive, compared with the predominance of Gram-negative species in the 1960s and 1970s.6-9 There are factors that account for this surge in Gram-positive infections. For example, intensive chemotherapy leads to damage of the mucosal barriers, which increases the risk of infection with Gram-positive oral (and GI) flora.6,10 In addition, the use of implantable intravenous catheters with cancer patients can facilitate the entry of organisms colonizing the skin into the bloodstream, and thus increase the rate of staphylococcal infections.6 Moreover, prophylactic antibiotics, which are active against Gram-negative enteric bacilli, exert a selective pressure that contributes to this increase in the rate of Gram-positive infections.6,11,12
This study explored the microbial spectrum of Gram-positive bacteria in cancer patients. We examined the spectrum of Gram-positive pathogens in various infection sites in patients with hematologic malignancies (mainly leukemia) and in patients with solid tumors. We devoted particular attention to infections caused by Coagulase-negative staphylococcus (CNS), Staphylococcus aureus, and Streptococcus species. This is because Staphylococcus species (such as CNS and S aureus) and Streptococcus species (such as
There are documented increasing rates of drug resistance among Gram-positive pathogens in cancer treatment centers.8,17,18 However, there is a shortage of literature covering antimicrobial resistance of bacterial isolates from cancer patients in hospitals and treatment centers in Egypt. Thus, the resistance patterns of hospital-acquired S aureus, CNS, and
Patient Samples Nonduplicate clinical specimens from urine, sputum, chest tube, bronchoalveolar lavage (BAL), pus, blood, throat swabs, and skin infection (SI) swabs were collected from patients at the National Cancer Institute (Cairo, Egypt). The SI swabs were obtained from cellulitis, wound infections, and perirectal infections. For each specimen type, only nonduplicate isolates were included (the first isolate per species per patient). Specimens were cultured on different media at 37°C. Data collected on each patient consisted of demographic data including age, admission date, ward, hospitalization duration, and sites of positive culture. Patients who had no evidence of infection on admission but developed signs of infection after at least 2 days of hospitalization were selected. Ethical approval to perform the study was obtained from the Egyptian Ministry of Health and Population. Patient consent was obtained before collection of specimens.
Microbial Identification
Biochemical Tests
Reagents
Antimicrobial Susceptibility Testing
Gram-positive bacteria isolated from different clinical specimens of cancer patients were mainly of streptococcal or staphylococcal species (Table 1). The main isolated Gram-positive bacteria from sputum were  -hemolytic streptococci (46.8%) and CNS (37.4%). As shown in Tables 1 and 2, the main isolated Gram-positive bacteria from blood were CNS (66.9%; 93 CNS isolates out of 139 total Gram-positive blood isolates), followed by S aureus (26.6%; 37 CNS isolates out of 139 total Gram-positive blood isolates). The main isolated Gram-positive bacteria from all specimens were CNS (46.5%; 350 out of 752 total Gram-positive isolates) followed by -hemolytic streptococci (29.4%) and S aureus (18.6%; Table 1).
The main CNS species isolated from clinical specimens were S hominis (12.7% of staphylococcal isolates from all clinical specimens) followed by S epidermidis (11.8%) and S haemolyticus (6.9%). The most predominant staphylococcal species isolated from the blood was S hominis (32.3%; 42 isolates out of 130 total staphylococcal blood isolates) followed by S aureus (28.5%; 37 isolates out of 130 total staphylococcal blood isolates). The most predominant Staphylococcal species from throat swabs was S epidermidis (24.1%; 23 isolates out of 96 total staphylococcal throat isolates) followed by S aureus (20.8%; 20 isolates out of 96 total staphylococcal throat isolates; Table 3).
Table 2 shows that, of 752 total Gram-positive isolates, 485 isolates (64.5%) were isolated from respiratory tract infections (RTIs). It is noteworthy that Gram-positive bacteria were not isolated from GI tract infections (GITIs). Of 485 Gram-positive isolates from RTI, 435 isolates were obtained from leukemic patients (89.7%), whereas only 50 isolates were obtained from solid-tumor patients (10.3%). Of 139 Gram-positive isolates from bloodstream infections (BSIs), 91 isolates were obtained from leukemic patients (65.5%), whereas only 48 isolates were obtained from solid-tumor patients (34.5%). Whereas all the 104 Gram-positive isolates from SIs were isolated from solid-tumor patients, all the 24 Gram-positive isolates from urinary tract infections (UTIs) were isolated from leukemic patients (Table 2).
In both leukemic patients and solid-tumor cancer patients, Gram-positive bacteria causing nosocomial BSI were mainly CNS (69.23% in leukemic patients, 62.5% in solid-tumor cancer patients) and S aureus (23.08% in case of leukemic patients, 33.34% in case of solid-tumor cancer patients; Table 4). In both cancer patient groups, the main etiologic CNS isolates were of S hominis species (27.47% in leukemic patients, 35.42% in solid-tumor cancer patients). In both leukemic patients and solid-tumor cancer patients, Gram-positive bacteria causing nosocomial RTIs were mainly
We examined the antimicrobial resistance patterns of different staphylococcal and streptococcal isolates from cancer patients (Tables 5 and 6). S aureus isolates were highly susceptible to linezolid (15.4% resistance), and vancomycin (15.5% resistance). They were still susceptible to few other antimicrobial agents such as cefoperazone (26.7% resistance), quinupristin/dalfopristin (28.6%), moxifloxacin (30.8%), rifampin (30.9%), chloramphenicol (32.3%), gatifloxacin (33.3%), cefotetan (45.8%), and levofloxacin (45.9%). However, they expected higher resistance to most other antimicrobial agents tested (Table 5). Similarly, CNS isolates exhibited 0% resistance to linezolid, and 11% resistance to vancomycin. They were still susceptible to few other antimicrobial agents such as Moxifloxacin (21.9% resistance), quinupristin/dalfopristin (22.6%), rifampin (24.2%), gatifloxacin (27.3%), chloramphenicol (36.4%), and levofloxacin (43.8%). However, they exhibited higher resistance to most other antimicrobial agents tested (Table 5). Isolates of -hemolytic streptococci were susceptible to cefoperazone (23.1% resistance), vancomycin (25%), ofloxacin (30.8%), rifampin (35.7%), and cefotetan (36.7%). We also examined resistance of Streptococcus species to other antimicrobial agents (Table 6). All of the staphylococcal and streptococcal isolates tested were resistant to oxacillin (Tables 5 and 6).
In accordance with reports indicating the evolving predominance of Gram-positive bacteria in cancer patients,6-8 we focused our study on characterizing the microbial spectrum of Gram-positive bacteria in cancer patients. As shown in Table 2, Gram-positive bacteria were the most common blood isolates from cancer patients (68.8%). This result was consistent with results from Lyytikainen et al,21 who reported that 65% of nosocomial BSI were caused by Gram-positive bacteria. In addition, Madani et al22 reported that Gram-positive bacteria represented 75% of total blood isolates in cancer patients. Moreover, the predominance of Gram-positive bacteria in isolates from cancer patients was shown in several other studies.6,9,23,24 For BSI, the main etiologic pathogens were CNS. Other studies have also reported CNS to be the most commonly isolated pathogen from blood.21,22 The overall spectrum of infections in cancer patients may be significantly different from that associated with BSI alone. Thus, this study not only examined BSIs but also RTIs, SIs, UTIs, and GITIs to get a complete picture of the microbial spectrum of Gram-positive bacteria in cancer patients. All of these infections can develop in cancer patients. The most prevalent Gram-positive bacteria in RTIs in cancer patients were from Streptococcus and Staphylococcus species, as was shown in other similar studies.25 The rate of SI (18%) was relatively higher than that reported in other studies.26 However, the study by Barber et al27 showed that the rate of SI in cancer patients could be highly variable over a wide range (3.9% up to 48.9%). The authors attributed this result to the variability of the type and duration of the surgical procedure involved.27 In this report, we showed that the most frequently isolated Gram-positive bacteria from SIs in cancer patients were S aureus and CNS. This finding was similar to the observation made by Vilar-Compte et al28 in their study of surgical site infections of cancer patients in Mexico.28 It is noteworthy that, in the present study, Streptococcus species infections caused the highest mortality rate (19.6%) in cancer patients, followed by S aureus and CNS infections (6.5% and 5.1%, respectively). Despite high mortality rates associated with nosocomial infections, data regarding endemic antimicrobial resistance are not available in countries where over-the-counter antibiotic use is common, as in Egypt.29 Our results indicated the presence of significant antimicrobial resistance to Gram-positive cocci (Staphylococcus and Streptococcus) in Cairo. This was consistent with what was reported by El-Kholy et al.29 In the present study, 81.5% of the isolated S aureus and 92.3% of the isolated CNS were methicillin resistant (Table 5). The contributions of methicillin-resistant S aureus (MRSA) and CNS to hospital-acquired infection were demonstrated previously.29-32 Cases of resistance to vancomycin, which was the drug of choice for treatment of patients with MRSA until recently, had been reported.33,34 Our study indicated the emergence of vancomycin resistance (15.5% resistance) in S aureus isolates (all of them were also methicillin resistant). To the best of our knowledge, this is the first report indicating the emergence of vancomycin-resistant S aureus (VRSA) in Egypt. A previous multi-center study in Egypt demonstrated that VRSA strains were absent from 1999 through 2000.29 The misuse of antibiotics in Egypt might have contributed to this rapid evolution of VRSA strains. Several studies suggested that linezolid was one of the few active drugs against vancomycin-resistant MRSA.35,36 Surprisingly, S aureus isolates from cancer patients in the present study were 15.1% resistant to linezolid. This further emphasized the important of sparing new effective antimicrobial agents and not using them routinely for the treatment of vancomycin-susceptible MRSA. Several reports suggested that newer generation quinolones (such as moxifloxacin and gatifloxacin) are more active against most Gram-positive pathogens than are older generation quinolones (such as ciprofloxacin and ofloxacin).37,38 Results in this study indicated that newer generation quinolones were more active than older generation quinolones against all examined staphylococcal species (S aureus and CNS). In the case of S aureus, percentages of resistance to moxifloxacin, gatifloxacin, levofloxacin, ciprofloxacin, and ofloxacin were 30.8%, 33.3%, 45.9%, 52.8%, and 60.9%, respectively. Similarly, percentages of resistance of CNS to moxifloxacin, gatifloxacin, levofloxacin, ciprofloxacin, and ofloxacin were 21.9%, 27.3%, 43.8%, 52.8%, and 53.1%, respectively. Studies by Rolston et al16 also showed that moxifloxacin and gatifloxacin had higher potency than second-generation quinolones (ciprofloxacin and ofloxacin) against Gram-positive bacteria isolated from cancer patients. This study suggests the importance of using newer generation quinolones, instead of older generation quinolones, in the prophylaxis of cancer patients. This is because of the mild effect of older generation quinolones on Gram-positive bacteria, which can contribute to the predominance of Gram-positive infections in cancer patients, as shown in this study and elsewhere.16,17,39 The continuous evolution of antimicrobial resistance patterns in bacteria necessitates continuous updating of data on antimicrobial susceptibility profiles to ensure the safety and efficacy of pathogen-specific antimicrobial therapies. To improve the outcome of treatment of nosocomial infections, antimicrobial restriction policies might help in limiting the emergence of resistant organisms. In addition, a comprehensive policy for infection control in hospitals must be designed and implemented to decrease the risk of nosocomial infections in cancer patients. When initiating empirical antibiotic therapy, clinicians should also take into consideration the entire microbial spectrum, and not just microbes associated with BSIs.
The author(s) indicated no potential conflicts of interest.
Conception and design: Hossam M. Ashour, Amany El-Sharif Provision of study materials or patients: Hossam M. Ashour, Amany El-Sharif Collection and assembly of data: Hossam M. Ashour, Amany El-Sharif Data analysis and interpretation: Hossam M. Ashour, Amany El-Sharif Manuscript writing: Hossam M. Ashour, Amany El-Sharif Final approval of manuscript: Hossam M. Ashour, Amany El-Sharif
We thank the medical staff of the National Cancer Institute (Cairo, Egypt) for assistance in sample collection.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
1. Andrei A, Zervos MJ: The application of molecular techniques to the study of hospital infection. Arch Pathol Lab Med 130:662-668, 2006[Medline] 2. Schabrun S, Chipchase L: Healthcare equipment as a source of nosocomial infection: A systematic review. J Hosp Infect 63:239-245, 2006[CrossRef][Medline] 3. Guinan JL, McGuckin M, Nowell PC: Management of health-care–associated infections in the oncology patient. Oncology (Williston Park) 17:415-420, 423-426, 2003[Medline] 4. Bodey GP: Managing infections in the immunocompromised patient. Clin Infect Dis 40:S239, 2005 (suppl)[CrossRef][Medline] 5. Berrouane YF, McNutt LA, Buschelman BJ, et al: Outbreak of severe Pseudomonas aeruginosa infections caused by a contaminated drain in a whirlpool bathtub. Clin Infect Dis 31:1331-1337, 2000[CrossRef][Medline] 6. Viscoli C, Varnier O, Machetti M: Infections in patients with febrile neutropenia: Epidemiology, microbiology, and risk stratification. Clin Infect Dis 40:S240-S245, 2005 (suppl)[CrossRef][Medline] 7. Wisplinghoff H, Seifert H, Wenzel RP, et al: Current trends in the epidemiology of nosocomial bloodstream infections in patients with hematological malignancies and solid neoplasms in hospitals in the United States. Clin Infect Dis 36:1103-1110, 2003[CrossRef][Medline] 8. Zinner SH: Changing epidemiology of infections in patients with neutropenia and cancer: Emphasis on Gram-positive and resistant bacteria. Clin Infect Dis 29:490-494, 1999[Medline] 9. Yadegarynia D, Tarrand J, Raad I, et al: Current spectrum of bacterial infections in patients with cancer. Clin Infect Dis 37:1144-1145, 2003[CrossRef][Medline] 10. Hughes WT, Armstrong D, Bodey GP, et al: 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 34:730-751, 2002[CrossRef][Medline] 11. Peshkin BN, Schwartz MD, Isaacs C, et al: Utilization of breast cancer screening in a clinically based sample of women after BRCA1/2 testing. Cancer Epidemiol Biomarkers Prev 11:1115-1118, 2002 12. Cruciani M, Rampazzo R, Malena M, et al: Prophylaxis with fluoroquinolones for bacterial infections in neutropenic patients: A meta-analysis. Clin Infect Dis 23:795-805, 1996[Medline] 13. Mutnick AH, Kirby JT, Jones RN: CANCER resistance surveillance program: Initial results from hematology-oncology centers in North America—Chemotherapy Alliance for Neutropenics and the Control of Emerging Resistance. Ann Pharmacother 37:47-56, 2003 14. Kumashi P, Girgawy E, Tarrand JJ, et al: Streptococcus pneumoniae bacteremia in patients with cancer: Disease characteristics and outcomes in the era of escalating drug resistance (1998-2002). Medicine (Baltimore) 84:303-312, 2005[CrossRef][Medline] 15. Ahmed R, Hassall T, Morland B, et al: Viridans streptococcus bacteremia in children on chemotherapy for cancer: An underestimated problem. Pediatr Hematol Oncol 20:439-444, 2003[Medline] 16. Rolston KV, Yadegarynia D, Kontoyiannis DP, et al: The spectrum of Gram-positive bloodstream infections in patients with hematologic malignancies, and the in vitro activity of various quinolones against Gram-positive bacteria isolated from cancer patients. Int J Infect Dis 10:223-230, 2006[CrossRef][Medline] 17. Diekema DJ, Jones RN, Rolston KV: Antimicrobial activity of gatifloxacin compared to seven other compounds tested against gram-positive organisms isolated at 10 cancer-treatment centers. Diagn Microbiol Infect Dis 34:37-43, 1999[Medline] 18. Diekema DJ, Coffman SL, Marshall SA, et al: Comparison of activities of broad-spectrum beta-lactam compounds against 1,128 gram-positive cocci recently isolated in cancer treatment centers. Antimicrob Agents Chemother 43:940-943, 1999 19. Drew WL, Barry AL, O'Toole R, et al: Reliability of the Kirby-Bauer disc diffusion method for detecting methicillin-resistant strains of Staphylococcus aureus. Appl Microbiol 24:240-247, 1972[Medline] 20. Cafferkey M: Methicillin-resistant Staphylococcus Aureus: Clinical Management and Laboratory Aspects (Infectious Disease and Therapy). New York, NY, Marcel Dekler Inc, 1992 21. Lyytikäinen O, Lumio J, Sarkkinen H, et al: Nosocomial bloodstream infections in Finnish hospitals during 1999-2000. Clin Infect Dis 35:e14-e19, 2002[CrossRef][Medline] 22. Madani TA: Clinical infections and bloodstream isolates associated with fever in patients undergoing chemotherapy for acute myeloid leukemia. Infection 28:367-373, 2000[CrossRef][Medline] 23. Friedman ND, Kaye KS, Stout JE, et al: Health care–associated bloodstream infections in adults: A reason to change the accepted definition of community-acquired infections. Ann Intern Med 137:791-797, 2002 24. Marchetti O, Calandra T: Infections in neutropenic cancer patients. Lancet 359:723-725, 2002[CrossRef][Medline] 25. Hoheisel G, Lange S, Winkler J, et al: Nosocomial pneumonias in haematological malignancies in the medical intensive care unit [in German]. Pneumologie 57:73-77, 2003[CrossRef][Medline] 26. Jesus Hernandez-Navarrete M, Arribas-Llorente JL, Solano-Bernad VM, et al: Quality improvement program of nosocomial infection in colorectal cancer surgery [in Spanish]. Med Clin (Barc) 125:521-524, 2005[CrossRef][Medline] 27. Barber GR, Miransky J, Brown AE, et al: Direct observations of surgical wound infections at a comprehensive cancer center. Arch Surg 130:1042-1047, 1995 28. Vilar-Compte D, Mohar A, Sandoval S, et al: Surgical site infections at the National Cancer Institute in Mexico: A case-control study. Am J Infect Control 28:14-20, 2000[CrossRef][Medline] 29. El Kholy A, Baseem H, Hall GS, et al: Antimicrobial resistance in Cairo, Egypt 1999-2000: A survey of five hospitals. J Antimicrob Chemother 51:625-630, 2003 30. Cepeda JA, Whitehouse T, Cooper B, et al: Isolation of patients in single rooms or cohorts to reduce spread of MRSA in intensive-care units: Prospective two-centre study. Lancet 365:295-304, 2005[Medline] 31. Melo-Cristino J: Antimicrobial resistance in staphylococci and enterococci in 10 Portuguese hospitals in 1996 and 1997: POSGAR—Portuguese Study Group of Antimicrobial Resistance. Microb Drug Resist 4:319-324, 1998[Medline] 32. Schmitz FJ, Lindenlauf E, Hofmann B, et al: The prevalence of low- and high-level mupirocin resistance in staphylococci from 19 European hospitals. J Antimicrob Chemother 42:489-495, 1998 33. Tiwari HK, Sen MR: Emergence of vancomycin resistant Staphylococcus aureus (VRSA) from a tertiary care hospital from northern part of India. BMC Infect Dis 6:156, 2006[CrossRef][Medline] 34. Appelbaum PC: The emergence of vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus. Clin Microbiol Infect 12:16-23, 2006 (suppl) 35. Stevens DL, Herr D, Lampiris H, et al: Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections. Clin Infect Dis 34:1481-1490, 2002[CrossRef][Medline] 36. Wunderink RG, Rello J, Cammarata SK, et al: Linezolid vs vancomycin: Analysis of two double-blind studies of patients with methicillin-resistant Staphylococcus aureus nosocomial pneumonia. Chest 124:1789-1797, 2003[CrossRef][Medline] 37. Rolston KV, Frisbee-Hume S, LeBlanc B, et al: In vitro antimicrobial activity of moxifloxacin compared to other quinolones against recent clinical bacterial isolates from hospitalized and community-based cancer patients. Diagn Microbiol Infect Dis 47:441-449, 2003[CrossRef][Medline] 38. Rolston KV, Vaziri I, Frisbee-Hume S, et al: In vitro antimicrobial activity of gatifloxacin compared with other quinolones against clinical isolates from cancer patients. Chemotherapy 50:214-220, 2004[CrossRef][Medline] 39. Diekema DJ, Beach ML, Pfaller MA, et al: Antimicrobial resistance in viridans group streptococci among patients with and without the diagnosis of cancer in the USA, Canada and Latin America. Clin Microbiol Infect 7:152-157, 2001[CrossRef][Medline] Submitted August 20, 2007; accepted September 20, 2007.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
TOP
ABSTRACT
INTRODUCTION
