sign in sign up
<<
Home , Nitrofurantoin

IABCR International Archives of BioMedical and Clinical Research www.iabcr.org

Research Article and Nitrofurantoin sensitivity pattern In Patients of (UTI) at a tertiary care teaching hospital Dharmesh Devmurari1*, Chand Miyaan Kamal2, Shambhu Nath Singh3, Amit Kumar4 1*Department of Microbiology, Gujrat Adani Institute of Medical Sciences, Bhuj, Gujarat. 2Department of Pharmacology, SMMH Government Medical College, Saharanpur, India 3Department of Pharmacology, Darbhanga Medical College and Hospital, Bihar. 4Department of Pharmacology, Teerthanker Mahaveer Medical College ______

Abstract Received: 12 Aug 2015 Introduction: UTIs are the second most common bacterial infection in present population. Revised: 14 Aug 2015 Women are more prone to UTI than Male. Uropathogenic is responsible for Accepted: 18 Aug 2015 >80% of community acquired UTIs. Aims: The present study was carried out to compare sensitivity / Resistance between Ofloxacin and Nitrofurantoin in UTI patients.

Methods: This was a prospective, cross-sectional, observatory study conducted on patients (n = 200) suffering from Urinary Tract Infection from March 2014 to February 2015 at the Department of Microbiology and Department of Pharmacology, Teerthanker Mahaveer Medical College and Research Centre (TMMC & RC), at a tertiary care teaching hospital, in Moradabad,

*Correspondence to: Uttar Pradesh, India. Dr Dharmesh Devmurari Results: UTI was much more common in females (61%, n=122) than in males (39%, n=78). Address: Department of The most common organism isolated was E. coli, 47%(n=94), followed by Klebsiella Microbiology, Gujrat Adani 34.5%(n=69), 7.5%(n=15), Proteus, 4%(n=8) and Institute of Medical Sciences, Bhuj, Gujarat. 3%(n=6). E. coli was highly sensitive to the Ofloxacin 18% (n=36). Email: Conclusion: Sensitivity pattern of the antimicrobial was found to be more in Nitrofurantoin [email protected] (57%) was found to be more sensitive than Ofloxacin (40.5%) for the treatment of UTI. Keywords: Nitrofurantoin, Ofloxacin, Antimicrobial agents, Sensitivity

Copyright: © publisher IABCR. This is an open access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction by Staphylococcus saprophyticus, Klebsiella pneumonia, UTIs are the second most common bacterial infection in and . [2] The organism present population. UTIs are one of the important causes of that caused urinary tract infection is those, which are morbidity and mortality in Indian population, affecting all normally present in renal area. E.coli, Klebsiella and age group across the life span. Nevertheless, it is a difficult Enterobacteria account for 90% of urinary tract infection. [3] to accurately assess the incidence of UTIs, because they are Proteus, Coagulase Negative Staphylococcus and not reportable diseases in the United States. This situation is Pseudomonas also cause urinary tract infection. [4] further complication by the fact that accurate diagnosis depend upon both the presence of symptoms and a positive UTI is defined by a combination of clinical feature and the culture, although in the most outpatient setting this the presence of bacteria in urine. It is also defined by the diagnosis is made without the benefit of culture. Women are presence of more than 100,000 colony –forming unit of significantly are more likely to experience UTI than man. single bacteria in culture in urine. The clinical feature of UTI Nearly 1 in 3 women will have had at least 1 episode of UTI may include both specific and nonspecific signs and requiring antimicrobial therapy by the age of 24 years. symptoms. Accurate diagnosis and treatment of UTI is Catheter-associated UTI is the Most common nosocomial essential to limit its associated morbidity, mortality and to infection, according for >1 million case in hospital and avoid prolonged or unnecessary use of . [5] nursing home. [1] Antibiotics for empiric treatment of uncomplicated UTI Uropathogenic Escherichia coli is responsible for >80% of include First-line : community acquired UTIs, with most other infection caused /Sulphamethoxazole (Cotrimoxazole) in

www.iabcr.org International Archives of BioMedical and Clinical Research | July-Sept 2015 | Vol 1 | Issue 1 17 | P a g e

Devmurari D et al. Int Arch BioMed Clin Res. 2015 Aug; 1(1):17-22 ] communities with resistance rates for E coli less than 20%. spp. (63%). There is no activity against Proteus spp. or P. Avoid in women who have been treated within 6 months, as Aeruginosa. [13] they are more likely to have resistant organisms. [6] Ofloxacin is a synthetic antibiotic of the Fluoroquinolones Second-line antibiotics: or first-line in resistant communities: drug class considered to be a second-generation Nitrofurantoin. Fluoroquinolones.[14] Ofloxacin is a broad-spectrum Fluoroquinolones, such as , , antibiotic that is active against both Gram-positive and , and Ofloxacin. Their efficacy is comparable to Gram-negative bacteria. Susceptible bacteria: co-trimoxazole, but increasing resistance rates have been noted. [7] Therefore the present study was carried out to compare sensitivity / Resistance between Ofloxacin and Alternates: third-generation Cephalosporin’s, Nitrofurantoin, Nitrofurantoin in UTI patients attending in Teerthanker Fosfomycin. Mahaveer Medical College and Research centre, Moradabad The following should not be used unless indicated by U.P. individual patient culture Sensitivities: first- or second- generation cephalosporin, Ampicillin and amoxicillin with Method Clavulate. [8] Study setting This was a prospective, cross-sectional, observatory study Single-dose regimens: Although single-dose therapy using β- conducted on patients (n = 200) suffering from Urinary Tract lactams, trimethoprim-, trimethoprim, and Infection from March 2014 to February 2015 at the Fluoroquinolones have shown high cure rates, single-dose Department of Microbiology and Department of therapy is associated with a high rate of recurrence within 6 Pharmacology, Teerthanker Mahaveer Medical College and weeks of initial treatment. Reinfection may be due to the Research Centre (TMMC & RC), at a tertiary care teaching failure of single-dose treatment to eradicate gram-negative hospital, in Moradabad, Uttar Pradesh, India. Patients were pathogens from the perianal area. Amino penicillin and first- recruited on the basis of inclusion and exclusion criteria. generation cephalosporin’s have shorter half-lives, which may contribute to their lower efficacy compared with other A total of 200 urine samples were collected and then agents. [9] transported to the Microbiology laboratory for culture and antimicrobial sensitivity test. Analyzation of data was carried In the treatment of urinary tract infections, the resolution of out on focusing on the gender, age, isolation of bacteria, bacteraemia has been correlated with the concentration of the gram staining and Antimicrobial sensitivity. antimicrobial agent in the urine rather than serum levels. [10] All the antimicrobial agents approved for the treatment of Data collection urinary tract infections achieve inhibitory urinary Analyzation of data was carried out on focusing on the concentrations that significantly exceed serum levels. gender, age, isolation of bacteria, and the antibiotic sensitivity data of all isolates was also reviewed and Nitrofurantoin, a chemotherapeutic compound of the analysed. family, was introduced into clinical practice in 1952. Nitrofurantoin is a synthetic antimicrobial derived Using a calibrated loop (volume - 0.005ml) streaking was from furan by the addition of a nitro group and a side chain done on cysteine lactose electrolyte containing hydantoin. Nitrofurantoin is a weak acid and its The isolated organism from culture plate was then assessed solubility is affected by PH. [11] for antimicrobial susceptibility test by disk diffusion method in Muller Hilton agar. Comparison was done by measuring Nitrofurantoin spectrum of in vitro susceptibility includes the the zone of inhibition between two antibiotics i.e. Ofloxacin majority of Escherichia coli, Citrobacter species, group B and Nitrofurantoin. Streptococci, Enterococci, , S. epidermidis, Klebsiella pneumoniae and Enterobacter Ethical approval species. [11] Thus, its antibacterial spectrum is broad and is Ethical approval for the study was obtained through the particularly effective against the main Uropathogen, hence Medical research and Ethics Committee at the Teerthanker its use for the treatment of urinary tract infections (UTI). In a Mahaveer Medical Collage and Research Centre (TMMC & recent study, the susceptibility for E. coli was 99.5%. High RC). susceptibility of E. coli clinical isolates to Nitrofurantoin (2.3% resistance rate), compared to Data analysis trimethoprim/sulfamethoxazole (29%) or ciprofloxacin Data were coded, checked for completeness and consistency. (24.2%) was recently confirmed.[12] However, Nitrofurantoin Then the data were entered and analysed into the computer is less susceptible against Gram-negative pathogens other by using Microsoft excel and SPSS 16.0. than E. coli, such as Klebsiella spp. (69.2%) or Enterobacter Comparative study of two antibiotics was done by using t- www.iabcr.org International Archives of BioMedical and Clinical Research | July-Sept 2015 | Vol 1 | Issue 1 18 | P a g e

Devmurari D et al. Int Arch BioMed Clin Res. 2015 Aug; 1(1):17-22 ]

test. Nitrofurantoin was found sensitive in n=114 (57%) cases.

Results E.coli were found highly sensitive to the The study reveals that urinary tract infection (UTI) was Nitrofurantoin n=65 (32.5%) samples, followed by the much more common in females (61%, n=122) than in males Klebsiella n=27 (13.5%) samples, staphylococcus (39%, n=78). The female sufferers were found more within 5.5%(n=11) cases, Proteus 3%(n=6) sample, pseudomonas the age group of (30-39) years (n=36), followed by the age 1.5%(n=3) sample and enterococcus were least sensitive in group (20-29) years (n=34), and males patients were found 1%(n=2) sample (Table 3, Fig. 3). more within the age group of (50-59) (n=20) years, followed by the age group (60-69) 7 %( n=14) (Table 1). Prevalence of Ofloxacin sensitivity against Uropathogens was found to be 40.5% (n=81). E. coli were sensitive to The incidence of UTI was maximum in age group the ofloxacin 18% (n=36) in out of 94 sample, followed by (20-29) year (23%, n=46), followed by the age group (30- the Klebsiella 14% (n=28) in out of 69 sample, 39) (21%, n=42), followed by the age group (50-59) (19% staphylococcus 3%(n=6) in out of 15sample, pseudomonas ,n=38), followed by the age group (40-49) (14% ,n=28), 2.5%(n=5) in out of 8 sample, Proteus 1.5% (n=3) in out of followed by the age group (10-19 & 60-69) (7% , n=14), 8 sample and enterococcus were least sensitive 1.5% (n=3) followed by the age group (<10) (6%, n=12), and age group in out of 6 sample (Table 4, Fig. 4). (70-79 & 80-89) years had the last percent 2,1% (n=2,4) respectively (Table 1, Fig. 1). Table 3:- distribution of isolated bacteria which sensitive Table 1: Demographic details of UTI patients to the nitrofurantoin

Organism Sensitive Resistance Total Age No. of Male Female Total range Patien NO. NO. (%) E.coli 65 29 94 (years) t (n) % % Klebsiella 27 42 69 Proteus 6 2 8 12 6(3%) 6(3%) 6% <10 Enterococcus 2 4 6 6(3%) 8(4%) 10-19 14 7% Pseudomonas 3 5 8 20-29 46 12(6%) 34(17%) 23% Staphylococcus 11 4 15 30-39 42 6(3%) 36(18%) 21% Total 114 86 200 40-49 28 8(4%) 20(10%) 14% 50-59 38 20(10%) 18(9%) 19% 60-69 14 14(7%) 0 7% Table 4:- distribution of isolated bacteria which sensitive 70-79 4 4(2%) 0 2% to the Ofloxacin 80-89 2 2(1%) 0 1% Organism Sensitive Resistance Total TOTAL 200 78(39%) 122(61%) 100% E.coli 36 58 94 The most common organism isolated was E. coli, Klebsiella 28 41 69 47%(n=94), followed by Klebsiella 34.5%(n=69), Proteus 3 5 8 staphylococcus 7.5%(n=15), Proteus, pseudomonas 4%(n=8) Enterococcus 3 3 6 Pseudomonas 5 3 8 and enterococcus 3%(n=6) (Table 2, Fig. 2). Staphylococcus 6 9 15 Total 81 119 200 Table 2: Total no. Of isolated organism obtained from urine Sample (n=200) Table 5:- compare the sensitivity between Ofloxacin and S.no. Organism Male Female Total nitrofurantoin drugs.

S. Organism Nitrofu Ofloxacin Total 1 E.coli 40 54 94 no rantoin 1 E.coli 65 36 94 2 Klebsiella 23 46 69 2 Klebsiella 27 28 69 3 Proteus 0 08 08 3 Proteus 6 3 08 4 Enterococcus 2 3 06 4 Enterococcus 4 02 06 5 Pseudomonas 3 5 08 5 Pseudomonas 4 04 08 6 Staphylococcus 11 6 15 7 Total 114 81 200 6 Staphylococcus 7 08 15

7 Total 78 122 200

www.iabcr.org International Archives of BioMedical and Clinical Research | July-Sept 2015 | Vol 1 | Issue 1 19 | P a g e

Devmurari D et al. Int Arch BioMed Clin Res. 2015 Aug; 1(1):17-22 ]

Fig. 4: Distribution of isolated bacteria which are Fig. 1: Showing the cases of UTI according to age group sensitive to Ofloxacin. of patients

Fig. 2: Total no. of isolate organism obtained from urine Fig. 5: Comparison of sensitivity between Ofloxacin and sample Nitrofurantoin drugs.

Discussion The present study revealed that urinary tract infection (UTI) was much more common in females 61% (n=122) than in males 39% (n=78). The female sufferers were mostly found within the age group of (30-39) years (18%, n=36), followed by the age group (20-29) years 17% (n=34), whereas in males, patients reported were mainly found within the age group of (50-59) years (10%, n=20), followed by the age group (60-69) (7%, n=13) (Table 1, Fig. 1). This fact was in accordance with the previous study done by the Jha N1, et al who showed that Urinary tract infection (UTI) was much more common in females than in males. Female sufferers were 53-80% and males were 20-47%, however, in hospital Tribhuwan University Teaching Hospital, Maharajgunj. The

female population was 80% and male was 20%. [15]

Fig. 3: Distribution of isolated bacteria which are A study done by the Dash M et al. Showed that most of the sensitive to Nitrofurantoin. UTI patients was female patients in the age range of 20-30 years with highest prevalence rate (27.8%) and then the least was found in age group more than 80 years, this might be www.iabcr.org International Archives of BioMedical and Clinical Research | July-Sept 2015 | Vol 1 | Issue 1 20 | P a g e

Devmurari D et al. Int Arch BioMed Clin Res. 2015 Aug; 1(1):17-22 ] due to reason that female in the reproductive age groups has And hence we suggest that physician should provide the use a high prevalence rate of UTI and similarly the incidence of of Nitrofurantoin in the treatment of Urinary tract infection symptomatic UTI is high in sexually active young women. patients gives better result than Ofloxacin in the same [16] patients for the requirement of the better results. There for based on the result from our study the demographic data showed that the sex and age of the patients Conclusion was similar to the study done by the Jha N1, et al and Therefore based on the result from our study we concluded slightly similar to the study done Dash M et al. [15,16] that the sensitivity pattern of the antimicrobial was found to be more in Nitrofurantoin (57%) than in their comparative For the pathogenic organism in UTI patients:- The present antimicrobial Ofloxacin (40.5%) for the treatment of the study showed that the most common organism was E. coli patients of UTI. 47% (n=94), followed by Klebsiella 34.5%(n=69), followed by staphylococcus 7.5%(n=15),followed by proteus and And also prescribing use of Nitrofurantoin was cost effective pseudomonas 4%(n=8) and enterococcus 3%(n=6). Similar then Ofloxacin. Hence we suggest that physician should findings were produced by Thapa P et al who showed that E. prescribe Nitrofurantoin in the treatment of Urinary tract coli (65.12%) was the most common pathogen causing UTI infection. followed by Staphylococcus species (11.63%), Proteus The present study emphasizes the need for constant species (6.98%), and Klebsiella species (6.4%). [17] monitoring failure the treatment and sensitivity of There for based on the result from the our study showed that Uropathogen in the region to commonly used anti-microbial the pathogenic organisms of the patients of UTI was slightly agents. Before starting the empirical therapy, knowledge of similar to the study done by the Jha N1, et al and P Thapa et etiology, predisposing, factors and susceptibility pattern of al. [15,17] the Uropathogen is essential to avoid the irrational antibiotics usage. There is a need for developing specific For the sensitivity of antimicrobial agents :- The present guideline for antibiotics usage for UTI in India. study showed that the antimicrobial sensitivity of Nitrofurantoin in the urine culture of the UTI patients were Limitation of our study is that sample size (n=200) of our 57% (n=114) sample in out of 200 sample, Among them study is small & sample is collected from one centre only. E.coli were 32.5%(n=65) sensitive in out of 94 sample, Small sample size study cannot confirm that Nitrofurantoin followed by the Klebsiella were 13.5%(n=27) in out of 69 is better than Ofloxacin. For confirmation of drug sensitivity, sample, followed by the staphylococcus were 5.5%(n=11) in samples should be collected from many centres and sample out of 15 sample, followed by the Proteus were 3%(n=6) in size should also be large. out of 8 sample followed by the pseudomonas were What this study adds: 1.5%(n=3) in out of 8 sample and enterococcus were 1%(n=2) in out of 6 sample. 1. What is known about this subject? Ofloxacin was more sensitive against gram negative bacteria. Whereas the antimicrobial sensitivity of Ofloxacin in the 2. What new information is offered in this study? urine culture of the UTI patients were 40.5% (n=81) sample Nitrofurantoin was found to be more sensitive than in out of 200 sample, Among them E. coli were 18% (n=36) Ofloxacin for the treatment of UTI. in out of 94 sample, followed by the Klebsiella were 14% ACKNOWLEDGEMENTS Declared none. (n=28) in out of 69 sample, followed by the staphylococcus CONFLICTS OF INTEREST None declared were 3%(n=6) in out of 15sample, followed by the FUNDING No funding source. pseudomonas were 2.5%(n=5) in out of 8 sample, followed ETHICS COMMITTEE APPROVAL Approved by the Proteus were 1.5% (n=3) in out of 8 sample, and enterococcus were 1.5% (n=3) in out of 6 sample. References 1. Foxman B, Freichs RR. Epidemiology of urinary tract Previous study for the sensitivity of antimicrobial in patients infection.II. Diet, clothing, and urination habits. Am J Public of UTIs, done by the Amit Raj Sharma et al showed that the Health. 1985; 17:1314-7. Majority of E. coli showed susceptibility towards 2. Ronald A. The etiology of urinary tract infection: nitrofurantoin (94.5%) followed by ciprofloxacin and traditional and emerging pathogens. Am J Med 2002; Ofloxacin with the susceptibility of 50.5% for each drug. [18] 113(Suppl 1):14S–19S There for based on the result from the our study showed that 3.Lucas MJ, Cunningham FC. Urinary tract infection during the sensitivity pattern of the antimicrobial was found to be pregnancy. ClinObstatGynecol.1993; 36:855. slightly more in Nitrofurantoin (57%) than in their 4. Davidson J &Bayles C; medical disorder in obstetric comparative antimicrobial Ofloxacin (40.5%) for the practice. Ed by Micheal de Swiet 4TH edition; Blackwell treatment of the patients of UTI which was slightly similar to publishing . 2002; 198-267, the study done by the Sharma AR et al and Thapa P et al. 5. Tanagho Emil A, Mcaninch, Jack W. Editors . smith`s [17,18] [Table 5, Fig. 5] general Urology. United States of America: McGraw-Hill www.iabcr.org International Archives of BioMedical and Clinical Research | July-Sept 2015 | Vol 1 | Issue 1 21 | P a g e

Devmurari D et al. Int Arch BioMed Clin Res. 2015 Aug; 1(1):17-22 ]

Companies Inc. Bacterial infection of the genitourinary tract. isolated from uninary tract infected patients attending Bir 2004; 203-227. hospital, Nepal. J Sci Technol. 2013;14(1):177–84. 6. Hooton TM, Stamm WE. Diagnosis and treatment of uncomplicated urinary tract infection. Infect Dis Clin North Cite this paper as: Am 1997; 11: 551-581. [PubMed] Devmurari D, Kamal CM, Singh SN, Kumar A.

7. Gupta K, Scholes D, Stamm WE. Increasing prevalence of Ofloxacin and Nitrofurantoin sensitivity pattern In antimicrobial resistance among uropathogens causing acute Patients of Urinary Tract Infection (UTI) at a tertiary care teaching hospital. Int Arch BioMed Clin Res. uncomplicated cystitis in women. JAMA 1999; 281: 736- 2015 Aug; 1(1):17-22 738. [PubMed] 8. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 91: treatment of urinary tract infections in non-pregnant women. Obstet Gynecol 2008;

111(3):785–94.

9. Hooton TM, Running K, Stamm WE. Single-dose therapy for cystitis in women: a comparison of trimethoprim- sulfamethoxazole, amoxicillin, and cyclacillin. JAMA 1985; 253: 387-390. [PubMed] 10. Stamey TA, Fair WR, Timothy MM, Millar MA, Mihara G, Lowery YC. Serum versus urinary antimicrobial concentrations in cure of urinary-tract infections. N Engl J Med 1974; 291: 1159-1163. [PubMed] 11. Cunha, B.A. Nitrofurantoin: An update. Obstet. Gynecol. Surv. 1989, 44, 399-406. 12. Kashanian, J.; Hakimian, P.; Blute, M., Jr.; Wong, J.; Khanna, H.; Wise, G.; Shabsigh, R. Nitrofurantoin: The return of an old friend in the wake of growing resistance.

BJU Int. 2008, 102, 1634–1637. 13. Mazzulli, T.; Skulnick, M.; Small, G.; Marshall, W.; Hoban, D.J.; Zhanel, G.G.; Finn, S.; Low, D.E. Susceptibility of community Gram-negative urinary tract isolates to mecillinam and other oral agents. Can. J. Infect. Dis. 2001, 12, 289–292.

14. Nelson, JM.; Chiller, TM. Powers, JH. Angulo, FJ. (Apr

2007). "Fluoroquinolone-resistant Campylobacter species and the withdrawal of fluoroquinolones from use in poultry: a public health success story". Clin Infect Dis 44 (7): 977– 80. doi:10.1086/512369. PMID 17342653. 15. Jha N, Bapat S K. A study of sensitivity and resistance of pathogenic microorganisms causing UTI in Kathmandu valley. Kathmandu University Medical Journal. 2005; Vol. 3,

No. 2, Issue 10, 123-129.

16. Dash M, Padhi S, Mohanty I, Panda P, Parida B. Antimicrobial Resistance in Pathogens Causing Urinary Tract Infections in a Rural Community of Odisha. India J Family Community Med. 2013; 20: 20-26. 17. Thapa P et al. Causative agents and susceptibility of antimicrobials among suspected females with urinary tract infection in tertiary care Hospitals of western Nepal. Journal of Chitwan Medical College. 2013; 3(4): 16-19. 18. Sharma AR, Bhatta DR, Shrestha J, Banjara MR. Antimicrobial susceptibility pattern of Escherichia coli

www.iabcr.org International Archives of BioMedical and Clinical Research | July-Sept 2015 | Vol 1 | Issue 1 22 | P a g e