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MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
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Dr. Mamta Gupta
Consultant
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Aug 2018




Dr. Rajendra Kumar Ghritlaharey

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Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
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Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2011 | Month : October | Volume : 5 | Issue : 5 | Page : 964 - 966 Full Version

Nitrofurantoin: An Alternative Therapy for Uncomplicated Cystitis in the Era of Antimicrobial Resistance


Published: October 1, 2011 | DOI: https://doi.org/10.7860/JCDR/2011/.1538
Asha Pai K.B., Rekha Rai, Sanjeev H., Vimal Kumar Karnaker, Krishna Prasad M.S.

1.MBBS, MD in Microbiology Assistant Professor of Microbiology K .S. Hegde Medical Academy Karnataka, India. 2. MBBS, MD in Microbiology Associate Professor of Microbiology K .S. Hegde Medical Academy Karnataka, India. 3. MBBS, MD in Microbiology Assistant Professor of Microbiology K .S. Hegde Medical Academy Karnataka, India. 4. MBBS, MD in Microbiology Professor of Microbiology K .S. Hegde Medical Academy Karnataka, India. 5. MBBS, MD in Microbiology Professorand HOD of Microbiology K .S. Hegde Medical Academy Karnataka, India

Correspondence Address :
1.MBBS, MD in Microbiology
Assistant Professor of Microbiology
K .S. Hegde Medical Academy
Karnataka, India.

Abstract

Introduction : Escherichia coli have been implicated as the commonest organism causing uncomplicated cystitis. The frequent irrational use of antibiotics has led to an increased prevalence of resistance to commonly used antibiotics like cotrimoxazole, Fluoroquinolones and β-lactams. Alternative antibiotic compounds are needed to treat such infections. This study was conducted to assess the prevalence of antimicrobial resistance among Escherichia coli causing cystitis and evaluate the sensitivitity of these strains to nitrofurantoin.

Material and methods: Three hundred and thirty two strains of Escherichia coli obtained from 2293 fresh midstream urine samples were included in the study. Antibiotic sensitivity testing was done byKirby Bauer disc diffusion method according to CLSI guidelines.

Results : Seven hundred and thirty six (32.09%) cases showed significant bacteriuria. A significant number of Escherichia coli isolates were found to be resistant to ciprofloxacin (72.59%), Norfloxacin (73.49%) and cotrimoxazole (71.38%). Over 90% of the strains were sensitive to nitrofurantoin. Two hundred and seventeen isolates (65.36%) were found to be ESBL producers by phenotypic confirmatory test. The ESBL producing isolates showed a high rate of sensitivity to ertapenem (96.77%), nitrofurantoin (88.94%) and amikacin (83.41%).

Conclusion: We consider that nitrofurantoin is a good alternative antibiotic to treat uncomplicated cystitis caused by antibiotic resistant Escherichia coli.

Keywords

Escherichia coli, uncomplicated cystitis, antimicrobial resistance, nitrofurantoin.

Introduction
Symptomatic urinary tract infection (UTI) is one of the most common infections, worldwide. Escherichia coli have been implicated as the commonest organism which causes uncomplicated cystitis. Antibiotics are the mainstay of the treatment for these infections. The frequent irrational use of these antibiotics has led to an increased prevalence of resistance to the commonly used antibiotics like cotrimoxazole, fluoroquinolones and β-lactams (1). Alternative antibiotic compounds are needed to treat such infections. This study was conducted to assess the prevalence of antimicrobial resistance among Escherichia coli which causes cystitis and to evaluate the sensitivitity of these strains to nitrofurantoin.

Material and Methods

This study was conducted at our teaching hospital from January 2010–December 2010. In-patients and out-patients with a clinical evidence of cystitis as determined by the treating physician were included in the study. Fresh, mid-stream urine (n =2293) was collected aseptically in sterile containers and it was submitted to the clinical microbiology laboratory. The samples which were received were inoculated onto blood agar and Cysteine Lactose Electrolyte Deficient (CLED) agar. After an overnight aerobic incubationat 37°C, the plates showing significant growth as per the Kass count (single species count of more than 10 (5) organisms per ml of urine) were processed further and the isolates were identified upto the species level by using standard biochemical tests. 332 strains of Escherichia coli which were thus obtained were included in the study. Antibiotic sensitivity testing was done by the Kirby Bauer disc diffusion method according to the CLSI guidelines (2). The antibiotics which were tested included ciprofloxacin (5 μg), norfloxacin (10 μg), cotrimoxazole (1.25/23.75 μg), nitrofurantoin (300 μg), amikacin (30 μg) and ertapenem (10 μg). The isolates were also tested for the production of extended spectrum beta lactamases (ESBL) according to the CLSI guidelines (2). Cefotaxime (30 μg), ceftazidime (30 μg) and ceftriaxone (30 μg) discs were used to screen for the ESBL production. The isolates which tested positive by the screening test were subjected to confirmatory test. Ceftazidime (30 μg) and ceftazidime /clavulanic acid (30 μg /10 μg) discs were used for the confirmatory test. The results were interpreted according to the CLSI guidelines (2).

Results

Out of the 2293 urine samples which were received, 736(32.09%) showed significant bacteriuria.

Escherichia coli was the commonest organism (n=332), constituting 45.10%

Out of the 332 isolates, 207(62.34%) were isolated from female patients and 125 (37.65%) from male patients.

The antibiotic susceptibility pattern of Escherichia coli is described in (Table/Fig 1).

The antibiotic sensitivity pattern of the ESBL producers and the non-ESBL producers is shown in (Table/Fig 2).

Discussion

Antimicrobial resistance is a growing problem of great concern throughout the world. For the treatment of the patients with cystitis, it is important to consider the local resistance patterns of the commonly isolated pathogens. This study provides an update on the sensitivity of Escherichia coli to the commonly used antibiotics.

In the 1990s The Infectious Diseases Society of America (IDSA) affirmed cotrimoxazole as a first line agent for the empirical therapy of uncomplicated cystitis in women in regions where the resistance was below 20% (3). The increased use of cotrimoxazole in the 1990s led to a high level of resistance worldwide. The prevalence of the resistance to cotrimoxazole among uropathogenic Escherichia coli now exceeds 65% in some regions of the world (4). The rates of resistance which have been reported in this study (71.38%) are comparable to those which are reported in the developing countries (69.5% in Madagascar, 67.8% in Senegal and 82% in India) and are much higher than those which have been reported in the developed countries (22.6% in USA, 17.3% in Canada, 21% in Russia and 26% in Spain) (4), (5),(6),(7),(8),(9). The extensive use of cotrimoxazole explains the high selection pressure for the resistant bacteria. The Infectious Diseases Society of America (IDSA) guidelines recommended an alternative therapy with fluoroquinolones, nitrofurantoin or fosfomycin in regions where the cotrimoxazole resistance exceeds 20% (3). Hence, cotrimoxazole is not recommended for empirical therapy in our region.

In the past few years, fluoroquinolones have been prescribed more frequently for the treatment of uncomplicated cystitis. This has resulted in an increase in the fluoroquinolone resistant Escherichia coli infections (10). The rate of resistance which has been reported in this study (ciprofloxacin-72.59%, norfloxacin-73.59%) is quite high and is comparable to those which are reported by Francesco MA et al (89.9%) and Tankhiwale SS et al. from India (69%) (7), (11). On the contrary, some studies have reported very low resistance rates to fluoroquinolones (Zhanel GG et al.-5.5%, Stratchounski LS et al 4.5%) (8), (12). The high fluoroquinolone resistance in our region might be due to the increased fluoroquinolone use over years, which has been necessitated by high cotrimoxazole resistance.

Aminoglycosides are effective against most of the bacteria which cause cystitis. They have a relatively narrow margin of safety between the therapeutic and the toxic concentrations. They exhibit ototoxicity and nephrotoxicity (13). They have to be administered parenterally, and are therefore not suitable for the treatment of the out-patients. In our study, 88.65 % were sensitive to Amikacin and it was a good choice for treating uncomplicated cystitis, especially in the in-patients.

With the increased use of cephalosporins, the frequency of the ESBL producing strains has increased in recent years. 65.36 % of the isolates were ESBL producers. This was much higher than that which was reported by Tankhiwale SS (18.5%) and Akram M (34.4%) and was comparable to the percentage from thereports from Narayanaswamy A et al (60%) and Mehrgan H. et al. (67.2 %) (7), (14),(15), (16). Previous studies from India have reported the ESBL production to vary from 28% to 84% (11). Our study reveals that a high percentage of the ESBL producing strains exhibit resistance to cotrimoxazole, ciprofloxacin and norfloxacin.

Carbapenems are the drug of choice for these strains, as these ESBL producers are frequently multidrug resistant (17). Our study has shown that 3.23% of the ESBL producing strains were resistant to ertapenem, which was congruent to the data which was provided by Eshwarappa M et al (3.9%) and lesser as compared to the data which was provided by Behera B et al (7%) (18),(19). Most of the other studies have reported 100% sensitivity to carbapenems (Khotari A etal, Mody RM et al) (20), (21). The disadvantages of using carbapenems include their high cost, their parental administration and the emergence of metallobetalactamases in Enterobacteriaceae. We did not screen these resistant isolates for metallobetalactamase production.

Nitrofurantoin has been used for more than five decades for the treatment of uncomplicated cystitis and it was found to remain active against most of the uropathogens, but its popularity was hampered by a recommended seven day dosing regimen and concerns about its efficacy and tolerance. A study which was conducted by Gupta K et al has revealed that, a 5-day course of nitrofurantoin was equivalent clinically and microbiologically to a 3-day course of cotrimoxazole and that it should hence be considered as an effective fluoroquinolone-sparing alternative for the treatment of acute cystitis in women (22). Nitrofurantoin was found to retain a good amount of sensitivity (90.98%), both against ESBL producers (88.94%) and non-ESBL producers (94.78%) in our study. This could be correlated with the reports by Kashanian et al. (95.6%) , Sire JM et al. (89.9%) and Karlowsky et al (98.3%) (1),(6), (23). The absorption of oral nitrofurantoin is 40-50% and hence, it is enhanced when it is taken with food. Its serum concentrations are very low to detect and its urine concentrations are 50-250mg/ml (24). The drug has minimal side effects on short course therapy. It can be used for treating uncomplicated cystitis, including the treatment of cystitis during pregnancy when it is clearly indicated (24).

Conclusion

The increased prevalence of antimicrobial resistance among Escherichia coli limits the therapeutic options considerably. Not only are the most β-lactams no longer active, but the associated co-resistance reduces the options even further. Alternative antimicrobial compounds are needed to treat the infections which are caused by such resistant organisms. We consider that nitrofurantoin is a good alternative antibiotic to treat uncomplicated cystitis which is caused by antibiotic resistant Escherichia coli.

Key Message

Uncomplicated cystitis is frequently caused by antibiotic resistant Escherichia coli. Alternative antibiotic compounds are needed to treat such infections. Nitrofurantoin is a good alternative antibiotic.

References

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Kashanian J, Hakimian P, Blute M, Wong J, Khanna H, Wise G et al. Nitrofurantoin: the return of an old friend in the wake of growing resistance. BJU International 2008; 102: 1634-1637.
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Waren JW, Abrutyn E, Hebel JR, Johnson JR, Schaeffer AJ, Stamm WE, et al. Guidelines for the antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. Infectious Disease Society of America (IDSA). Clin Infect Dis 1999; 29: 745-58.
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Sire JM, Nabeth P, Perrier-Gros-Claude JD, Bahsoun I, Siby T, Macondo EA, et al. Antimicrobial resistance in outpatient Escherichia coli urinary isolates in Dakar, Senegal. J Infect Developing Countries 2007; 1(3): 263-68.
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Stratchounski LS, Rafalski VV. Antimicrobial susceptibility of the pathogens which were isolated from adult patients with uncomplicated, community-acquired urinary tract infections in the Russian federation: two multicentre studies, UTIAP-1 and UTIAP-2. Int J Antimicrob Agents 2006; 28(1):S4-S9.
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Gobernado M, Valdes L, Alos JI, Garcia-Rey C, Dal-Re R, Garcia-de- Lomas J, et al. Antimicrobial susceptibility of clinical Escherichia coli isolates from uncomplicated cystitis in women over a 1-year period in Spain. Rev Esp Quimioter 2007; 20:68-76.
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Karaca Y, Coplu N, Gozalan A. Cotrimoxazole and quinolones resistance in Escherichia coli which was isolated from urinary tractinfections over the last 10 years. Int J Antimicrobial Agents 2005; 26: 75-77.
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Frencesco MA, Ravizalla G, Peroni L. Urinary tract infections in Brescia, Italy: the aetiology of the uropathogens and the antimicrobial resistance of the common uropathogens. Med Sci Monit, 2007: 13(6): BRI 36-44.
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Zhanel GG. Antibiotic resistance in outpatient urinary isolates: final results from the North American Urinary Tract Infection Collaboration Alliance (NAUTICA). Int J Antimicrob Agents 2005; 26:380-388.
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Tripati KD. Aminoglycosides. In: Tripati M, Tripati V editors. Essentials of medical pharmacology. New Delhi: Jaypee brothers, 1999; p.730-738.
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Akram M, Shahid M, Khan AU. The aetiology and the antibiotic resistance patterns of community-acquired urinary tract infections in the JNMC Hospital Aligarh, India. Ann Clinl Microbiol Antimicrob 2007; 6:4.
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