Home | Volume 22 | Article number 87

Original article

Susceptibility pattern of uropathogens to ciprofloxacin at the Ghana police hospital

Susceptibility pattern of uropathogens to ciprofloxacin at the Ghana police hospital

 

Daniel Kwame Afriyie1,&, Martha Gyansa-Lutterodt3, Seth Kwabena Amponsah2, George Asare4, Vanessa Wiredu1, Edem Wormenor1, Kwasi Agyei Bugyei2

 

1Ghana Police Hospital, Pharmacy Department, Accra, Ghana, 2Department of Pharmacology and Toxicology, University of Ghana School of Pharmacy, Accra, Ghana, 3Ministry of Health, Accra, Ghana, 4School of Biomedical and Allied Health Sciences, University of Ghana

 

 

&Corresponding author
Daniel Kwame Afriyie, Ghana Police Hospital, Pharmacy Department, PMB CT 104, Accra, Ghana

 

 

Abstract

Introduction: reports of increasing resistance of uropathogens to antimicrobials is of global concern. Culture and drug susceptibility tests remain a vital guide to effective therapy. The aim of this study was to determine the susceptibility pattern of isolated uropathogens to ciprofloxacin at the Ghana Police Hospital.

 

Methods: a total of 705 mid-stream urine samples were collected from patients suspected of having urinary tract infection, and visited the Ghana Police Hospital's laboratory from December 2013 to March 2014. Samples were cultured and isolates identified by standard methods, after which isolates susceptibility to ciprofloxacin was determined.

 

Results: prevalence of urinary tract infection among patients' whose samples were analyzed was 15.9%. Predominant uropathogens isolated were E .coli (46.4%), Coliform (41.1%) and Coliform spp. with Candida (6.2%). Other isolates were Pseudomonas spp. (2.7%), Salmonella spp. (1.8%), Candida spp. (0.9%) and Klebsiella spp (0.9%). The overall resistance among the top three isolated uropathogens to ciprofloxacin was 35.9%. Resistance pattern demonstrated by respective isolates to ciprofloxacin were: E. coli (38.5%), Coliform (54.3%), and Coliform spp. with Candida (15%). The other isolates showed 100% sensitivity.

 

Conclusion: this study revealed a relatively high ciprofloxacin resistance among isolated uropathogens, hence, the need for prudent prescribing and use of ciprofloxacin in urinary tract infection management.

 

 

Introduction

Urinary tract infections (UTIs) are common among inpatients and outpatients, ranking second only to respiratory infections [1]. Worldwide, Escherichia coli (E. coli) and Staphylococcus saprophyticus are among the predominant isolates of UTIs [2]. Other bacterial isolates found in Sub-Saharan Africa include Klebsiella pneumonia, Proteus mirabilis, Staphylococcus aureus, Pseudomas aeruginosa and Enteroeaseus feacalis [3-5]. Increasing microbial resistance to conventional antibiotics like beta-lactams, aminoglcosides, sulfonamides and cephalosporins used in UTI management necessitated the use of other agents such as macrolides and fluoroquinolones.

 

Since their introduction, fluoroquinolones have become a mainstay in the treatment of bacterial infections [6, 7]. Fluoroquinolones are often preferred as first line agents in the management of UTIs, especially when antimicrobial resistance is of concern [8, 9]. They are also recommended where conventional agents are less desirable due to toxicity or hypersensitivity concerns [10]. Ciprofloxacin is the most frequently prescribed fluoroquinolone for UTIs because of its availability in oral and intravenous formulations, favorable bioavailability, and pharmacokinetics which allows twice-daily administration [11, 12]. Resistance to fluoroquinolones has increased markedly since their introduction for treatment of UTI. Rattanaumpawan et al, documented fluoroquinolone resistance of 15.8% and 57.4% among E. coli and A. baumannii respectively [13]. In Africa, substandard drugs, indiscriminate use of antibiotics and erratic prescription by unqualified drug sellers have been identified as contributing to emergence of resistance [14]. Evidence of increasing resistance to ciprofloxacin in some communities is also documented [15, 16]. A recent antimicrobial susceptibility study of isolated uropathogens at the Ghana Police Hospital revealed high resistance to conventional antibiotics [17]. Changes in drug resistance pattern among uropathogens have led to reassessment of local antimicrobial agents [18]. Currently, very little data is available on the susceptibility pattern of uropathogens to ciprofloxacin in Ghana, although the drug is recommended in the national treatment guidelines for UTI management. The aim of this study was to determine the susceptibility pattern of recently isolated uropathogens to ciprofloxacin at the Ghana Police Hospital.

 

 

Methods

Study population

 

This was a cross-sectional study that involved analyzing 705 urine samples of suspected UTI patients, who visited the Ghana Police Hospital's laboratory from December 2013 to March 2014. The population consisted of both in- and out-patients.

 

Sample collection and processing

 

Midstream urine samples were collected in sterile urine containers. With a calibrated wire, a loop-full (0.01 ml) of urine was inoculated onto a quarter-plate of Cysteine Lactose Electrolyte-Deficient agar (CLED) (Biotic Laboratories Ltd, U.K) and incubated at 37°C for 24 hours in Nodermann GMBH incubator (Germany). After incubation period, colonies were enumerated and those with significant growth identified. Significant microbial growth was categorized by microbial count greater than 1x105 cfu/ml. Microbial colonies were identified biochemically and serologically according to standard methods [19]. Isolates were speciated by routine procedures which included colonial characteristics, gram-staining, coagulase test and API 20 system. Each colony, representing an isolate was emulsified in 2 ml sterile peptone water, and then transferred into sensitivity agar plates (Biotec laboratories, UK).

 

Susceptibility Testing

 

Susceptibility test was with the Kirby-Bauer disc diffusion method using sensitivity agar (Oxoid, UK) and pertinent antibiotics emphasizing ciprofloxacin with a break point of 5 μg. Inhibition zone diameters pertaining to ciprofloxacin were measured using calipers and compared with standard interpretation charts [20] and scored as sensitive or resistant.

 

Data analysis

 

Data were checked for completeness, entered, and analyzed using SPSS version 20 (Armonk, NY: IBM Corp). Chi-square (χ²) was used to test for association and a p value less than 0.05 was considered statistically significant.

 

Ethical issues

 

Protocol for this study was approved by the Ghana Police Hospital Administration.

 

 

Results

Out of the 705 urine samples analyzed, 374 (53%) were obtained from females whilst 331 (47%) were from males. Samples with significant microbial growth (>1x105 cfu/ml) constituted 112 (15.9%), as shown in Table 1. Results also showed a higher incidence (p<0.0001) of UTI among females 84 (75%) than in male subjects 28 (25%). Predominant uropathogens isolated were E .coli 52 (46.4%) and Coliform 46 (41.1%). Other isolates found in this study; Pseudomonas spp., Salmonella spp., Candida spp., Klebsiella, and Coliform spp. with Candida are presented in Table 2.

 

Table 3 shows the sensitivity pattern of microbial isolates to ciprofloxacin. E. coli, Coliform spp, and mixed Coliform + Candida spp. which together constitute 93.7% of total isolates showed sensitivities of 61.5%, 45.7% and 85% to ciprofloxacin respectively. Overall resistance among the top three isolated uropathogens to ciprofloxacin was 35.9%. The rest of the isolates; Pseudomonas spp., Salmonella spp., Candida spp. and Klebsiella which constituted 6.3 % of total isolates showed 100% sensitivity to ciprofloxacin.

 

 

Discussion

This study showed UTI prevalence rate of 15.9%, and its incidence was significantly higher in female than in males. Prevalence rate in this study was lower than findings of 31.6% from a study at the Ghana Police hospital in 2011 [17], and from a similar study in Ghana that reported 56.5% [4]. Multiple predisposing factors have been identified to contribute to higher prevalence among females. A major factor being anatomical differences in the urogenital organs between the two sexes; shorter urethra in females allows quicker access of bacteria to the urinary system [21]. Furthermore, poor personal hygiene coupled with certain cultural practices [22], may account for a higher incidence in women. On the other hand, the antibacterial activity of prostatic fluid in males makes them less susceptible to UTI [23]. Common bacteria isolated from cultures in studies conducted among UTI patients in Ghana include E. coli, Klebsiella, Candida and Salmonella spp [24, 25]. This study revealed that, E. coli and other coliform isolates constituted 87.2% of the total microbial isolates. Pseudomonas spp, Klebsiella spp, Candida spp and Salmonella spp are others identified among isolates with significant growth. These isolates are similar to those reported in studies done in Ghana [3, 4, 24, 25] and elsewhere [2, 5]. Furthermore, in the current study the two most common isolated uropathogens are the same reported in an earlier study conducted at the Ghana Police Hospital, although their frequencies varied [17]. Also in the previous study, Staphylococcus aureus and Providencia were identified among uropathogens.

 

Incidence of Candida spp (6.2%), and mixed Candida with Coliform (0.9%) in this study was higher than 5.3% reported in a study conducted in Nigeria [26], and above the range (0.14-0.77%) from studies in Israel and Italy [27, 28]. Prevalence of yeast among isolates in the current study was lower than the 11% obtained from a similar study conducted in Kumasi, Ghana [25]. This finding suggests that, clinicians should consider treating possible underlying fungal infections especially when empirical treatment fails in recurrent UTIs. Due to the fact that resistance to antifungals among yeast has been linked to misuse and inappropriate prescription of antifungals [29], medical practitioners should only initiate empirical antifungal treatment when microbial susceptibility tests are unavailable.

 

Fluoroquinolones are preferred in the treatment of UTI because they have a high bacteriologic and clinical cure rates, as well as low rates of resistance among most common uropathogens [30]. A review of susceptibility trends of uropathogens to ciprofloxacin in the 1990s showed high sensitivities of 93.9% for Enterobacteriaceae, 81.8% for P. aeruginosa 90.2% for gram positive aerobes [31], and 80% for gram-negative isolates [32]. The overall sensitivity (64.1%) of the top three isolated uropathogens to ciprofloxacin observed in this study was lower than findings from similar studies [31, 32]. Recently, ciprofloxacin resistant uropathogens have been reported in a number of countries. Those reported include 15 % in a study in Turkey [33], 15% in Gaza [12], 14.7% in Spain [15], 33.3% in Nigeria [5], 28.6% in Iran [34], and rates of 46.6 to 59.4% in China [35]. Another study in South Africa revealed ciprofloxacin resistance of 11% for isolates from uncomplicated UTI and 41% for isolates from complicated UTI [36]. Additionally, the overall resistance (35.9%) of the top three uropathogens to ciprofloxacin in this study was relatively high compared with other studies [5, 12, 33, 34]. Although the causative microorganisms of UTI keeps changing over the years, E. coli and Enterobacteriaceae remain the most common uropathogens, accounting for about 75-90% of laboratory culture isolates [2]. E. coli resistance to ciprofloxacin (38.5%) observed in this study, was lower than the 46.7% observed in a similar study in Ethiopia [37]. However, E. coli resistance to ciprofloxacin in this study was higher than similar studies; 32 % in Kumasi, Ghana [38], 11% from nine out of ten regions in Ghana [24], 33% in Ethiopia [39], and 22% in Switzerland [40].

 

In a related study that assessed fecal E. coli susceptibility to quinolones between the years 2006 and 2007, it was observed that 13 (52%) of the isolates were resistant to ciprofloxacin, whilst in 2008, 10 (67%) resistant [41]. Although the number of fecal E. coli isolates in these studies are fewer than that of isolated from urine, ciprofloxacin resistance among urine E. coli appears to be lower than those observed in fecal isolates. Since E. coli has been found to be the causative microorganism in over 70% of UTIs worldwide, its resistance to ciprofloxacin observed in this study, and other similar studies in Ghana should be of concern to medical practitioners and drug policy makers. Studies have shown that, pressure on drugs used in therapy can influence resistance pattern of causative organisms than intrinsic bacterial protective mechanisms [42]. In Ghana, the broad therapeutic indications of ciprofloxacin; typhoid fever, infectious diarrhoea, lower respiratory-tract infections, gastro-enteritis, cholera, gonorrhea among others [43], exerts pressure on its use, and increases its risk of misuse. Additionally, although a prescription drug, ciprofloxacin can be obtained over the counter in a number of pharmacies in Ghana, and this further contributes to its misuse.

 

 

Conclusion

The relatively high ciprofloxacin resistance demonstrated by the most predominant isolates, Coliform spp. and E. coli, in this study should be of great concern to medical practitioners, drug regulatory agencies and policy makers. This emphasizes the need for continuous evaluation of the quality of common antibiotics, prudent drug prescription and judicious use of ciprofloxacin in UTI management.

 

 

Competing interests

The authors declare no competings interest.

 

 

Authors’ contributions

Conception and design of study: Daniel Kwame Afriyie, Martha Gyansa-Lutterodt and Seth Kwabena Amponsah. Data acquisition: Edem Wormenor and Vanessa Wiredu. Analysis and interpretation: Daniel Kwame Afriyie, George Asare, Kwasi Agyei Bugyei and Seth Kwabena Amponsah. All authors were part of drafting and revising of this manuscript. All authors have read and approved the final version of this manuscript.

 

 

Acknowledgments

The authors are grateful to the Ghana Police Hospital for technical support given this project.

 

 

Tables

Table 1: level of microbial growth among UTI patients (n = 705)

Table 2: frequency and percent of microbial isolates with significant growth

Table 3: sensitivity of isolates to ciprofloxacin

 

 

References

  1. Foxman B, Brown P. Epidemiology of urinary tract infections: transmission and risk factors, incidence, and costs. Infect Dis Clin North Am. 2003; 17(2): 227-24. PubMed | Google Scholar

  2. Gupta K. Addressing antibiotic resistance. Dis Mon. 2003; 49(2):99-110. PubMed | Google Scholar

  3. Adjei O, Opoku C. Urinary tract infections in African infants. Int J Antimicrob Agents. 2004; 24 (1):32-34. PubMed | Google Scholar

  4. Boye A, Siakwa PM, Boampong JN, Koffour GA, Ephraim RKD, Amoateng P, Obodai G, Penu D. Asymptomatic urinary tract infections in pregnant women attending antenatal clinic in Cape Coast, Ghana. J Med Res. 2012; 1(6):74-83. PubMed | Google Scholar

  5. Onoh RC, Umeora OUJ, Egwuatu VE, Ezeonu PO, Onoh TJP. Antibiotic sensitivity pattern of uropathogens from pregnant women with urinary tract infection in Abakaliki, Nigeria. Infect Drug Resist. 2013; 6:225-233. PubMed | Google Scholar

  6. Sharma PC, Jain A, Jain S, Pahwa R, Yar MS. Ciprofloxacin: review on developments in synthetic, analytical, and medicinal aspects. J Enz Inhib Med Chem. 2010; 25(4):577-589. PubMed | Google Scholar

  7. Sharma PC, Saneja A, Jain S. Norfloxacin: A therapeutic review. Int J Chem Sci. 2008; 6(4):1702-1713. PubMed | Google Scholar

  8. Drago L, De Vecchi E, Mombelli B, Nicola L, Valli M, Gismondo MR. Activity of levofloxacin and ciprofloxacin against urinary pathogens. J Antimicrob Chemother. 2001; 48(1):37?45. PubMed | Google Scholar

  9. Schaeffer AJ. The expanding role of fluoroquinolones. Am J Med. 2002; 113(suppl 1A):45S-54S. PubMed | Google Scholar

  10. Carson C, Naber KG. Role of fluoroquinolone in the treatment of serious bacterial urinary tract infections. Drugs. 2004; 64 (12):1359-1373. PubMed | Google Scholar

  11. Kamberi M, Tsutsumi K, Kotegawa T, Kawano K, Nakamura K, Niki Y, Nakano S. Influences of urinary pH on ciprofloxacin pharmacokinetics in humans and antimicrobial activity in vitro versus those of sparfloxacin. Antimicrob Agents Chemother. 1999; 43 (3):525-529. PubMed | Google Scholar

  12. Astal ZE. Increasing ciprofloxacin resistance among prevalent urinary tract bacterial isolates in Gaza Strip, Palestine. J Biomed Biotechnol. 2005; 3:238-241. PubMed | Google Scholar

  13. Rattanaumpawana P, Tolomeoa P, Bilkera WB, Fishman NO, Lautenbacha E. Risk factors for fluoroquinolone resistance in Gram-negative bacilli causing healthcare-acquired urinary tract infections. J Hosp Infect. 2010; 76(4): 324-327. PubMed | Google Scholar

  14. Chinedum IE. Microbial resistance to antibiotics. Afr J Biotechnol. 2005; 4(13):1606-1611. PubMed | Google Scholar

  15. Kahlmeter G. An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECO SENS Project. J Antimicrob Chemother. 2003; 51(1):69?76. PubMed | Google Scholar

  16. Iqbal J, Rahman M, Kabir MS, Rahman M. Increasing ciprofloxacin resistance among prevalent urinary tract bacterial isolates in Bangladesh. Jpn J Med Sci Biol. 1997; 50(6):241-250. PubMed | Google Scholar

  17. Gyansa-Lutterodt M, Afriyie DK, Asare G, Amponsah SK, Abutiate H, Darko D. Antimicrobial use and susceptibility pattern of uropathogens associated with urinary tract infections at the Ghana Police Hospital. GJP. 8 (3); 306-315, 2014. PubMed | Google Scholar

  18. Astal Z, Sharif FA, Abdallah SA, Fahd MI. Multiresistant Escherichia coli isolated from women with community-acquired urinary tract infections in the Gaza Strip. J Chemother. 2002; 14 (6):637-638. PubMed | Google Scholar

  19. Murray PR, Baron EJ, Pfaller MA, Tenover FC, Yolken RH. Manual of Clinical Microbiology. ASM Press, Washington, DC. 1995; 6th Edition. Google Scholar

  20. Chesbrough, M. District Laboratory Practice in Tropical Countries- Cambridge University Press. 2002; Part 2. Google Scholar

  21. Gupta K, Scholes D, Stamm, WE. Increasing prevalence of antimicrobial resistance among uropathogens causing uncomplicated cystitis in women. JAMA. 1999; 281(8): 736-738. PubMed | Google Scholar

  22. Johnson JR, Stamm WE. Urinary Tract Infections in Women: Diagnosis and Treatment. An Int Med. 1989; 111:109-117. PubMed | Google Scholar

  23. Lipsky BA. Urinary tract infections in men: epidemiology, pathophysiology, diagnosis, and treatment. Ann Intern Med. 1989; 110(2): 138-150. PubMed | Google Scholar

  24. Newman MJ, Frimpong E, Sampane-Donkor E, Opintan JA, Asamoah-Adu A. Resistance to antimicrobial drugs in Ghana. Infect Drug Resist. 2011; 4:215?220. PubMed | Google Scholar

  25. Feglo PK, Narkwa P. Prevalence and antifungal susceptibility patterns of yeast isolates at the Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana. Br Microbiol Res J. 2012; 2(1):10-22. PubMed | Google Scholar

  26. Iregu KC, Nwajiobi-Princewill PI. Urinary tract infections in a tertiary hospital in Abuja, Nigeria. Afr J Clin Exper Microbiol. 2013; 14(3):169-173. PubMed | Google Scholar

  27. Navarro EE, Almario JD, King C, Bacher J, Pizzo PA, Walsh TJ. Detection of Candida casts in experimental renal candidiasis: implications for the diagnosis and pathogenesis of upper urinary tract infection. J Med Vet Mycol. 1994; 32:415-426. PubMed | Google Scholar

  28. Colodner R, Nuri Y, Chazan B and Raz R. Community-acquired and hospital acquired candiduria: comparison of prevalence and clinical characteristics. Eur J Clin Microbiol Infect Dis. 2008; 27:301-305. PubMed | Google Scholar

  29. Pfaller MA, Messer SA, Boyken L, Rice C, Tendolkar S, Hollis RJ, Doem GV, Diekema DJ. Global trends in the antifungal susceptibility of Cryptococcus neoformans (1990 to 2004). J Clin Microbiol. 2005; 43(5):2163-2167. PubMed | Google Scholar

  30. Schaeffer AJ. The expanding role of fluoroquinolones. Am J Med. 2002; 113 (suppl 1A):45S-54S. PubMed | Google Scholar

  31. Van poppel H, Chysky V, Hullmann R, Baert L. Clinical experience with ciprofloxacin in the treatment of urinary tract infections: a review. Infection. 1998; 16(6):337-344. PubMed | Google Scholar

  32. Iqbal J, Rahman M, Kabir MS, Rahman M. Increasing ciprofloxacin resistance among prevalent urinary tract bacterial isolates in Bangladesh. Jpn J Med Sci Biol. 1997; 50(6):241-250. PubMed | Google Scholar

  33. Eryilmaz M, Bozkurt ME, Yildiz MM, Akin A. Antimicrobial resistance of urinary Escherichia coli isolates. Trop J Pharm Res. 2010; 9:205-209. PubMed | Google Scholar

  34. Sarrafzadeh F, Sohrevardi SM. Evaluation of bactereuria and antimicrobial Susceptibility among hospitalized patients with and without catheter in Kerman Province- Iran in 2011. IJPR. 2013; 12 (1):211-216. PubMed | Google Scholar

  35. Shao HF, Wang WP, Zhang XW, Li ZD. Distribution and resistance trends of pathogens from urinary tract infections and impact on management. Zhonghua Nan Ke Xue. 2003; 9(9): 690-692. PubMed | Google Scholar

  36. Bosch FJ, Vuuren CV, Joubert G. Antimicrobial resistance patterns in outpatient urinary tract infections - the constant need to revise prescribing habits. S Afr Med J. 2011; 101:328-331. PubMed | Google Scholar

  37. Tiruneh M, Yifru S, Gizachew M, Molla K, Belyhun Y, Moges F, Endris M. Changing trends in prevalence and antibiotics resistance of uropathogens in patients attending the Gondar University Hospital, Northwest Ethiopia. Int J Syst Bacteriol. 2014; Article ID 629424: 7 pages. PubMed | Google Scholar

  38. Duredoh Fg, Gbedema SY, Agyare C et al. Antibiotic Resistance Patterns of Escherichia coli Isolates from Hospitals in Kumasi, Ghana. ISRN Microbiol. 2012; Article ID 658470, 5 pages. PubMed | Google Scholar

  39. Yismaw G, Abay S, Asrat D, Yifru S, Kassu A. Bacteriological profile and resistant pattern of clinical isolates from pediatric patients, Gondar University Teaching Hospital, Gondar, Northwest Ethiopia. Ethiop Med J. 2010; 48(4):293-300. PubMed | Google Scholar

  40. Nicoletti J, Kuster SP, Sulser T, Zbinden R, Ruef C, Ledergerber B, Weber R. Risk factors for urinary tract infections due to ciprofloxacin-resistant Escherichia coli in a tertiary care urology department in Switzerland. Swiss Med Wkly. 2010; 140:w13059. PubMed | Google Scholar

  41. Namboodiri SS, Opintan JA, Lijek RS, Newman MJ, Okeke IN. Quinolone resistance in Escherichia coli from Accra, Ghana. BMC Microbiol. 2011; 11:44. PubMed | Google Scholar

  42. Acar JF, Goldstein FW. Consequences of increasing resistance to antimicrobial agents. Clin Infect Dis. 1998; 27(1):125-130. PubMed | Google Scholar

  43. Standard Treatment Guidelines. Sixth Edition. Ghana. 2010. Google Scholar