Resistance pattern in UTI: Indian and International perspectives

Epidemiology of Urinary Tract Infections

Urinary tract infection (UTI) is commonly encountered by clinicians worldwide. It is caused by pathogenic invasion of the urinary tract system, spanning from urethra, urinary bladder, ureter to kidney. Traditionally, it may be classified (table 1), depending upon the site of infection as upper UTI (infection of the kidney and ureter) or lower UTI (infection of the urinary bladder and urethra); depending upon the presence or absence of symptoms as symptomatic or asymptomatic UTI; depending upon the factors that trigger it as complicated or uncomplicated UTI. Of special note, diagnosis of UTI requires demonstration of bacteriuria (table 1).¹Vasudevan R. Urinary Tract Infection: An Overview of the Infection and the Associated Risk Factors. J Microbiol Exp. 2014;1(2):00008.  ^,2Rowe TA, Juthani-Mehta M. Diagnosis and Management of Urinary Tract Infection in Older Adults. Infect Dis Clin North Am. 2014;28(1):75-89.

The worldwide high incidence of UTI in both community and hospital settings makes it an issue of major public concern; its global burden can be estimated from the observations that annually symptomatic UTI alone is responsible for 7 million outpatient visits, 1 million emergency department visits and 100,000 hospitalizations.³Beyene G, Tsegaye W. Bacterial Uropathogens in Urinary Tract Infection and Antibiotic Susceptibility Pattern in Jimma University Specialized Hospital, Southwest Ethiopia. Ethiop J Health Sci. 2011;21(2):141-146.   Hence, in the contemporary era of rampant antimicrobial resistance, these pervasive infections which are highly recurrent not only contribute to considerable morbidity and financial burden but may incur mortality as well, particularly in hospitalized patients.^4-84) Sharma I, Paul D. Prevalence of community acquired urinary tract infections in Silchar Medical College, Assam, India and its antimicrobial susceptibility profile. Indian Journal of Medical Sciences. 2012;66(11):273-279.
5) Flores-Mireles AL, Walker JN, Caparon M, et al. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol. 2015;13(5):269-84.
6) Hsueh PR, Hoban DJ, Carmeli Y, et al. Consensus review of the epidemiology and appropriate antimicrobial therapy of complicated urinary tract infections in Asia-Pacific region. J Infect. 2011 Aug;63(2):114-23.
7) Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Dis Mon. 2003 Feb;49(2):53-70.
8) Sumati AH, Saritha NK. Association of Urinary Tract Infection in Women with Bacterial Vaginosis. J Glob Infect Dis. 2009;1(2):151-152.

A recent Indian study noted the prevalence of UTI in females vs males in outpatient department to be 73.57% vs 35.14%, respectively (figure 1). Further analysis by age-group revealed the incidence of UTI to be highest in females in reproductive age group; refer to figure 2 for objective findings.⁹Prakash D, Saxena RS. Distribution and Antimicrobial Susceptibility Pattern of Bacterial Pathogens Causing Urinary Tract Infection in Urban Community of Meerut City, India. ISRN Microbiology. 2013;Volume 2013:Article ID 749629.   However, this gender disparity in the rate of UTIs appears to narrow with the advancing age, and the elderly men and women show comparable frequency of UTI.¹⁰Harrington RD, Hooton TM. Urinary tract infection risk factors and gender. J Gend Specif Med. 2000 Nov-Dec;3(8):27-34.   While pelvic prolapse, lack of antiinflammatory estrogenic milieu, loss of lactobacilli in the vaginal flora, increased periurethral colonization by Escherichia coli, and agerelated medical conditions (e.g., diabetes) are the prime reasons for UTIs in postmenopausal women, prostatic diseases (e.g. benign prostatic hyperplasia) and age-related medical conditions tend to make aging men increasingly susceptible to UTIs.¹¹Al-Badr A, Al-Shaikh G. Recurrent Urinary Tract Infections Management in Women A review. Sultan Qaboos Univ Med J. 2013;13(3):359-367.  ^,12Beveridge LA, Davey PG, Phillips G, et al. Optimal management of urinary tract infections in older people. Clin Interv Aging. 2011; 6: 173-180.   Apart from the adult and geriatric population, UTIs are also common in children in whom they can cause acute and chronic morbidity.¹³Ma JF, Shortliffe LM. Urinary tract infection in children: etiology and epidemiology. Urol Clin North Am. 2004;31(3):517-26, ix-x.   Contribution of UTIs to childhood morbidity may be underscored from the fact that they account for fever in 10% of all febrile children, 13.6% of all febrile infants and 7% of all febrile newborns.¹⁴Nickavar A, Sotoudeh K. Treatment and Prophylaxis in Pediatric Urinary Tract Infection. Int J Prev Med. 2011;2(1):4-9.

Overall, the aggregate analysis of the above discussion indicates pervasive prevalence of UTI across all ages and both genders, albeit significantly higher in females of reproductive age group.

Common Pathogens Causing Urinary Tract Infections

Diagnosis and treatment of UTIs in the initial stages, i.e., when the infection is limited to the lower urinary tract, is important to circumvent the risk of complications, including death, that are associated with the infection that has progressed to the renal tissues. The diagnosis of UTI can be dependably made by the presence of significant bacteriuria in clean catch samples of adequately collected quantitative urine cultures. However, since culture and sensitivity results may take a couple of days before any conclusive information is obtainable, it is suggested that empiric antibiotic therapy, depending upon the local antibiotic susceptibility and resistance patterns of the prevalent uropathogens, should be initiated without delay. Therefore, it is crucial that the treating physician is equipped with the knowledge of the prevalent uropathogens and their susceptibility patterns in order to initiate appropriate empiric antibiotic treatment.¹Vasudevan R. Urinary Tract Infection: An Overview of the Infection and the Associated Risk Factors. J Microbiol Exp. 2014;1(2):00008.  ^,15Lo DS, Shieh HH, Betta Ragazzi SP, et al. Community-acquired urinary tract infection: age and gender-dependent etiology. J Bras Nefrol. 2013;35(2):93-98.

Among the plethora of microorganisms (bacteria, fungus, and virus) that may cause UTI, bacteria are the most common culprits. The bacterial spectrum encompasses Gram-negative as well as Grampositive pathogens, including E. coli, Klebsiella pneumoniae, Staphylococcus saprophyticus, Proteus mirabilis and Enterococcus faecalis. Generally, E. coli (Gram-negative) is the most frequently isolated uropathogen from both hospital and community UTI patients, accounting for 80-85% cases.¹Vasudevan R. Urinary Tract Infection: An Overview of the Infection and the Associated Risk Factors. J Microbiol Exp. 2014;1(2):00008.  ^,5Flores-Mireles AL, Walker JN, Caparon M, et al. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol. 2015;13(5):269-84.  ^,11Al-Badr A, Al-Shaikh G. Recurrent Urinary Tract Infections Management in Women A review. Sultan Qaboos Univ Med J. 2013;13(3):359-367.  ^,16Olorunmola FO, Kolawole DO, Lamikanra A. Antibiotic resistance and virulence properties in Escherichia Coli strains from cases of urinary tract infections. Afr. J. Infect. Dis. 2013;7(1):1-7.

Several national and international populationbased studies have evaluated the spectrum of bacterial pathogens isolated from the patients with UTI. In one such study conducted in rural Odisha, India, the investigators documented E. coli to be the predominant isolate in patients with communityacquired UTI (68.8%), followed by Enterococcus spp. (9.7%); table 2.¹⁷Dash M, Padhi S, Mohanty I, et al. Antimicrobial resistance in pathogens causing urinary tract infections in a rural community of Odisha, India. J Family Community Med. 2013;20(1):20-26.   Similarly, another study from a tertiary care hospital in North West India recorded E. coli as the most prevalent isolate (45.7%) in patients with community- or hospital-acquired UTI, followed by Coagulase-negative Staphylococci (18.6%) and Klebsiella spp. (8.3%).¹⁸Singhal A, Sharma R, Jain M, et al. Hospital and Community Isolates of Uropathogens and their Antibiotic Sensitivity Pattern from a Tertiary Care Hospital in North West India. Ann Med Health Sci Res. 2014 Jan-Feb; 4(1): 51-56.   A data from South India (Karnataka) also showed E. coli to be the common uropathogen isolated from patients with UTI (table 3).¹⁹Patil S, Mahale K, Shetty P, et al. Antibiotic susceptibility pattern of urinary isolates from a tertiary care hospital with special reference to Gram negative bacteria. IOSR Journal of Dental and Medical Sciences. 2013;12(1):49-51.   The studies from other parts of the Asia, such as Iran and Singapore, have identically documented E. coli as the predominant urinary isolate in patients with UTI, followed by Klebsiella spp.^20-2220) Behzadi P, Behzadi E, Yazdanbod H, et al. A survey on urinary tract infections associated with the three most common uropathogenic bacteria. Maedica (Buchar). 2010;5(2):111-115.
21) Kargar M, Kargar M, Jahromi MZ, et al. Molecular detection of ESBLs production and antibiotic resistance patterns in Gram negative bacilli isolated from urinary tract infections. Indian J Pathol Microbiol. 2014;57(2):244-8.
22) Bahadin J, Teo SS, Mathew S. Aetiology of community-acquired urinary tract infection and antimicrobial susceptibility patterns of uropathogens isolated. Singapore Med J. 2011;52(6):415.     Records from African countries, such as Ethiopia, also reflect similar findings, showing E. coli to be the leading cause of UTIs (33.3%), followed by K. pneumoniae (19%) and S. saprophyticus (14.3%).3 In a similar manner, epidemiological studies in South American nations have charted the frequency of most common uropathogens in UTIs in descending order as E. coli (56%), Klebsiella spp. (18%) and Enterobacter spp. (11%).²³Matute AJ, Hak E, Schurink CA, et al. Resistance of uropathogens in symptomatic urinary tract infections in León, Nicaragua. Int J Antimicrob Agents. 2004;23(5):506-9.   In the western hemisphere of the globe (e.g., USA) also, E. coli isolates have been documented as the predominant pathogens in UTI.²⁴Sabharwal ER. Antibiotic Susceptibility Patterns of Uropathogens in Obstetric Patients. N Am J Med Sci. 2012;4(7):316-319.

Antibiotic Resistance in Uropathogens

Urinary tract infections (UTIs) are one of the most common reasons for antibiotic prescription in outpatient as well as inpatient settings. Depending upon the patient’s age, sex, underlying disease, infecting agent and the site of infection, a panel of antibiotics, including nitrofurantoin, fluoroquinolones, cephalosporins, other β-lactams with or without β-lactamase inhibitors are commonly prescribed to treat these infections. However, their inadvertent use has led to the emergence of resistant strains which can withstand these antibiotics and continue to thrive and multiply in the adverse environments engendered by them.¹Vasudevan R. Urinary Tract Infection: An Overview of the Infection and the Associated Risk Factors. J Microbiol Exp. 2014;1(2):00008.  ^,25Mandal J, Acharya NS, Buddhapriya D, et al. Antibiotic resistance pattern among common bacterial uropathogens with a special reference to ciprofloxacin resistant Escherichia coli. Indian J Med Res. 2012;136:842-849.   This apart, the constantly evolving ability of these pathogens to resist antibiotic attack and transmit these evolved features to other species has also aided in the development and spread of antibiotic resistance. Additionally, the rising emergence of resistant bacterial strains in animals due to increasing use of antimicrobials for the prevention and treatment of infectious diseases in them has also contributed in escalating the burden of resistant strains in humans, since animal bacteria can be easily transmitted to humans either directly or via consumption of animal products.²⁶Allocati N, Masulli M, Alexeyev MF, et al. Escherichia coli in Europe: An Overview. Int. J. Environ. Res. Public Health. 2013;10:6235-6254.

The important mechanisms of antibiotic resistance development in bacteria include reduced antimicrobial uptake, enzymatic modification and degradation to inactivate antibiotic, altered

penicillin-binding proteins (PBPs) reducing binding of antibiotic to the target cells, efflux pumps effluxing the antibiotic out of bacterial cells, altered antibiotic targets and target overproduction. A bacteria may be either intrinsically exhibiting these mechanisms (e.g., E. coli is intrinsically resistant to vancomycin and therapeutic levels of penicillin G) or acquire them.²⁶Allocati N, Masulli M, Alexeyev MF, et al. Escherichia coli in Europe: An Overview. Int. J. Environ. Res. Public Health. 2013;10:6235-6254.  ^,27Giedraitiené A, Vitkauskiené A, Naginiené R, et al. Antibiotic Resistance Mechanisms of Clinically Important Bacteria. Medicina (Kaunas). 2011;47(3):137-46.

Apropos to the subject of acquired resistance in E. coli, horizontal transfer of genes located on mobile genetic elements, including plasmids, integrons and transposons, is very important. Refer to table 4 for comprehensive overview of resistance mechanisms in Gram-negative uropathogens in UTI.²⁶Allocati N, Masulli M, Alexeyev MF, et al. Escherichia coli in Europe: An Overview. Int. J. Environ. Res. Public Health. 2013;10:6235-6254.  ^,27Giedraitiené A, Vitkauskiené A, Naginiené R, et al. Antibiotic Resistance Mechanisms of Clinically Important Bacteria. Medicina (Kaunas). 2011;47(3):137-46.

Antibiotic Resistance Patterns in UTI and its Clinical Implications : Global Perspective

As elaborated in the sections above, UTIs are frequently encountered infections in community as well as hospital settings, and E. coli is the leading cause of these infections. However, inappropriate use of antibiotics has led to the emergence and spread of resilient uropathogens, which have evolved adaptive mechanisms to resist antibiotic insult, thereby rendering them ineffective. The challenge of antibiotic resistant uropathogens is common to both the developed and the developing nations. Therefore, it becomes pertinent that local antibiotic susceptibility and resistance patterns of the most frequent uropathogens implicated in UTI, i.e., E. coli, are continuously evaluated and reevaluated to help tailor appropriate empiric antimicrobial treatment.²⁵Mandal J, Acharya NS, Buddhapriya D, et al. Antibiotic resistance pattern among common bacterial uropathogens with a special reference to ciprofloxacin resistant Escherichia coli. Indian J Med Res. 2012;136:842-849.

In U.S., researchers have noted that over the last several years uropathogenic E. coli has developed significant resistance to the commonly used empiric antibiotic treatments for UTI, including amoxicillin, trimethoprim-sulfamethoxazole (TMP-SMX) and fluoroquinolones.²⁸Olson RP, Harrell LJ, Kaye KS. Antibiotic Resistance in Urinary Isolates of Escherichia coli from College Women with Urinary Tract Infections. Antimicrob Agents Chemother. 2009 Mar; 53(3): 1285-1286.   Analysis of US Surveillance Network Database from January 1 to September 30, 2000 pertaining to the resistance patterns in urinary isolates of E. coli in UTI patients against the commonly used antibiotics (including ampicillin, cephalothin, ciprofloxacin, nitrofurantoin and TMPSMX) revealed resistance rates of 92.8% to TMP-SMX, 86.6% to cephalothin, 38.8% to ciprofloxacin and 7.1% to two or three drugs (the leading phenotype of multidrug-resistant isolates was resistance to ampicillin, cephalothin and TMP-SMX). Notably, the least rate of resistance was to nitrofurantoin – 7.7%.²⁹Sahm DF, Thornsberry C, Mayfield DC, et al. Multidrug-Resistant Urinary Tract Isolates of Escherichia coli: Prevalence and Patient Demographics in the United States in 2000. Antimicrob Agents Chemother. 2001;45(5):1402-1406.   In sync with these findings, a retrospective collegebased study in southeastern US which evaluated antibiotic resistance patterns in E. coli – the most frequently isolated uropathogen from young women students with UTI – documented ampicillin resistance in 37% students, TMP-SMX resistance in 29.6% students, ciprofloxacin resistance in 6.8% students and nitrofurantoin resistance in none of the students (figure 3). Additionally, ampicillin resistance was noted in 34.5% episodes among patients with prior history of UTI and 45.6% episodes among patients without prior history of UTI. TMP-SMX and ciprofloxacin resistance was documented in 26.9% and 11.8% episodes among patients with prior history of UTI, respectively, and 38.6% and 1.8% episodes among patients without prior history of UTI, respectively. Interestingly, nitrofurantoin resistance was noted in none of the UTI episodes. The study authors concluded that despite increasing emergence of resistance to the commonly used antibiotics for uropathogens in UTI, nitrofurantoin has retained its efficacy and should therefore be strongly recommended as the first-line empiric therapy for the treatment of uncomplicated UTIs.²⁸Olson RP, Harrell LJ, Kaye KS. Antibiotic Resistance in Urinary Isolates of Escherichia coli from College Women with Urinary Tract Infections. Antimicrob Agents Chemother. 2009 Mar; 53(3): 1285-1286.

Similar resistance trends have been observed in Europe as well where treatment of UTI has been complicated by emergence of multidrug resistant isolates of E. coli.²⁶Allocati N, Masulli M, Alexeyev MF, et al. Escherichia coli in Europe: An Overview. Int. J. Environ. Res. Public Health. 2013;10:6235-6254.   In West Ireland, >50% of the E. coli isolates were found resistant to ampicillin, >40% to sulphonamide, >30% to trimethoprim and 7.9%-12.5% to amoxicillin-clavulanic acid combination. The susceptibility levels in the region were highest for nitrofurantoin (96.7%), followed by nalidixic acid (93.9%) and ciprofloxacin (94.7%).³⁰Chulain MN, Murray AM, Corbett-Feeney G, et al. Antimicrobial resistance in E.coli associated with urinary tract infection in the west of Ireland. Ir J Med Sci. 2005;174(4):6-9.   Table 5 enlists resistance rates of E. coli to a panel of antibiotics in various European countries.²⁶Allocati N, Masulli M, Alexeyev MF, et al. Escherichia coli in Europe: An Overview. Int. J. Environ. Res. Public Health. 2013;10:6235-6254.

In Latin American nations too high resistance rates of uropathogens to the commonly prescribed antibiotics have been registered by several investigators. For example, Maute and colleagues in Nicaragua observed high resistance rates of E. coli – the most frequently isolated uropathogen in symptomatic UTI patients – to amoxicillin (82%), TMP-SMX (64%), cephalothin (58%), ciprofloxacin (30%), amoxicillin-clavulanic acid (21%) and gentamicin (12%). Remarkably, >90% of the E. coli isolates were susceptible to nitrofurantoin, ceftriaxone and amikacin.²³Matute AJ, Hak E, Schurink CA, et al. Resistance of uropathogens in symptomatic urinary tract infections in León, Nicaragua. Int J Antimicrob Agents. 2004;23(5):506-9.

In African continent as well increasing incidence of resistance of urinary pathogens to the commonly prescribed antibiotics for UTI is being witnessed. In Jimma University Specialized Hospital, Southwest Ethiopia, uropathogens isolated from patients with UTIs showed high resistance rates against several commonly prescribed antibiotics. E. coli which was the leading uropathogen isolated, however, demonstrated no resistance against nitrofurantoin, nalidixic acid, gentamicin and ceftriaxone.³Beyene G, Tsegaye W. Bacterial Uropathogens in Urinary Tract Infection and Antibiotic Susceptibility Pattern in Jimma University Specialized Hospital, Southwest Ethiopia. Ethiop J Health Sci. 2011;21(2):141-146.   In certain parts of Nigeria too, alarmingly high resistance rates of the frequently isolated uropathogen in UTI (E. coli) to all commonly used antibiotics, except nitrofurantoin, has been reported. Olorunmola and colleagues noted the rate of resistance of E. coli urinary isolates from Nigeria patients with UTI to range between 51.1% and 96.4% for all commonly used antibiotics (11 antibiotics were tested), except nitrofurantoin (7.3%) (figure 4). Occurrence of multidrug resistance was reflected by 14.6%, 14.14%, 9.5% and 5.8% of the E. coli isolates being resistant to 7, 8, 9 and all 11 antibiotics, respectively.¹⁶Olorunmola FO, Kolawole DO, Lamikanra A. Antibiotic resistance and virulence properties in Escherichia Coli strains from cases of urinary tract infections. Afr. J. Infect. Dis. 2013;7(1):1-7.   Affirming high nitrofurantoin

sensitivity of urinary E. coli isolates, another study from the same region showed 80% of these pathogens to be sensitive to nitrofurantoin, 24% to ofloxacin, 15% to ciprofloxacin, 10% to nalidixic acid, 5% to TMP-SMX and 2% to amoxicillin-clavulanic acid combination.³¹Aboderin OA, Abdu AR, Odetoyin BW, et al. Antimicrobial resistance in Escherichia coli strains from urinary tract infections. J Natl Med Assoc. 2009;101(12):1268-73.   South African investigators too have reported significantly high rate of resistance of urinary E. coli isolates to the commonly utilized antibiotics, except nitrofurantoin. Bosch and colleagues reported the level of resistance in uncomplicated UTIs as 54% to TMP-SMX, 46% to amoxicillin and 11% to each nitrofurantoin and ciprofloxacin; in complicated UTIs, these rates were 68% to TMP-SMX, 65% to amoxicillin, 41% to ciprofloxacin and 27% to nitrofurantoin. Overall, all E. coli UTI isolates were found sensitive to nitrofurantoin.³²Bosch FJ, van Vuuren C, Joubert G. Antimicrobial resistance patterns in outpatient urinary tract infections–the constant need to revise prescribing habits. S Afr Med J. 2011 May;101(5):328-31.

Focusing attention towards the resistance patterns of uropathogens in Asia to the commonly used antibiotics, a Singaporean study which evaluated the local antibacterial susceptibility of uropathogens in culture-positive, community-acquired UTIs found E. coli (the most frequently isolated uropathogen) to be most sensitive to nitrofurantoin and significantly resistant to ampicillin, TMP-SMX, ciprofloxacin and cephalothin (figure 5).²²Bahadin J, Teo SS, Mathew S. Aetiology of community-acquired urinary tract infection and antimicrobial susceptibility patterns of uropathogens isolated. Singapore Med J. 2011;52(6):415.   In the Middle East Asian region of Iran too, E. coli strains from patients with UTI have been showing high resistance rates to tetracycline (95.16%), nalidixic acid (89.78%) and gentamicin (73.20%).²¹Kargar M, Kargar M, Jahromi MZ, et al. Molecular detection of ESBLs production and antibiotic resistance patterns in Gram negative bacilli isolated from urinary tract infections. Indian J Pathol Microbiol. 2014;57(2):244-8.

The overall analysis of the aforementioned information conclusively suggests that the most prevalent urinary pathogens contributing to UTI in either community or hospital settings have become increasingly resistant to the frequently prescribed antibiotics, except nitrofurantoin which continues to register significant sensitivity against them and therefore retains its relevance as empiric therapy for the treatment of UTI.³³McKinnell JA, Stollenwerk NS, Jung CW, et al. Nitrofurantoin Compares Favorably to Recommended Agents as Empirical Treatment of Uncomplicated Urinary Tract Infections in a Decision and Cost Analysis. Mayo Clin Proc. 2011;86(6):480-488.

Antibiotic Resistance Patterns in UTI and its Clinical Implications : Indian Perspective

Similar to the global trends, in India too UTI pathogens have been showing significant resistance to the commonly prescribed antibiotics. In fact, published reports indicate that the prevalence of ESBL-producing urinary E. coli in Asia Pacific is highest in India at 60%.⁶Hsueh PR, Hoban DJ, Carmeli Y, et al. Consensus review of the epidemiology and appropriate antimicrobial therapy of complicated urinary tract infections in Asia-Pacific region. J Infect. 2011 Aug;63(2):114-23.

Patil and colleagues evaluated antibiotic susceptibility patterns of the most frequently isolated uropathogens from UTI patients attending a tertiary care center in Karnataka (South India). While Gram-negative pathogens in both inpatients and outpatients showed least resistance to nitrofurantoin, the greatest resistance was registered to ampicillin and TMP-SMX (figure 6).¹⁹Patil S, Mahale K, Shetty P, et al. Antibiotic susceptibility pattern of urinary isolates from a tertiary care hospital with special reference to Gram negative bacteria. IOSR Journal of Dental and Medical Sciences. 2013;12(1):49-51.   Another group of investigators from the same region likewise assessed antibiotic resistance patterns among the most frequently isolated uropathogens in UTI – E. coli. From among a host of antibiotics tested for resistance and sensitivity, both ESBL- and non-ESBLproducing E. coli demonstrated least resistance and significant sensitivity to nitrofurantoin and ertapenem (Figure 7&8). The experts further expressed their preference for nitrofurantoin over ertapenem (a carbapenem) for uncomplicated UTIs, citing high cost, parental administration and the emergence of metallo-beta-lactamases in Enterobacteriaceae with carbapenem group of antibiotics as the reasons for their nitrofurantoin preference. They went on to discuss that inadvertent use of TMP-SMX as empiric therapy for the treatment of uncomplicated UTI since 1990s has led to high global resistance rates which in some regions of the world have exceeded 65%. They further stated that accordingly the Infectious Disease

Society of America (IDSA) has recommended alternative therapy with other antimicrobials, such as nitrofurantoin, in regions where resistance to TMP-SMX is >20%.³⁴Pai Asha KB, Rai R, Sanjeev H, et al. Nitrofurantoin: An Alternative Therapy for Uncomplicated Cystitis in the Era of Antimicrobial Resistance. Journal of Clinical and Diagnostic Research. 2011;5(5):964-966.   In another region of South India (Tamil Nadu), similar findings were reverberated by Sangeeth and colleagues in their population-based study in which they documented significant resistance of uropathogenic E. coli to a panel of antibiotics, except nitrofurantoin and amikacin.³⁵Sangeeth K, Rajesh KR, Indrapriyadharsini R. Antibiotic resistance pattern of Escherichia coli causing urinary tract infection with an emphasis on fluoroquinolone resistance. Global Journal of Medicine and Public Health. 2014;3(1).

Indian studies from Vidarbha region (Maharashtra) likewise have noted resistance levels of urinary E. coli isolates to be least for nitrofurantoin (figure 9).³⁶Ghanwate NA. Biofilm eradication studies on uropathogenic E. coli using ciprofloxacin and nitrofurantoin. Int J Pharm Biomed Res. 2012;3(2):127-131.

In North West India too researchers have documented least resistance rates of uropathogens to nitrofurantoin (19.8%), followed by cefoperazone plus sulbactam combination (22%) and amikacin (32.4%), whereas high levels of resistance have been documented against fluoroquinolones (70.3%) and cephalosporins (75.1%).¹⁸Singhal A, Sharma R, Jain M, et al. Hospital and Community Isolates of Uropathogens and their Antibiotic Sensitivity Pattern from a Tertiary Care Hospital in North West India. Ann Med Health Sci Res. 2014 Jan-Feb; 4(1): 51-56.

Reports from North India also indicate similar antibiotic resistance and sensitivity patterns among the bacterial uropathogens in UTI. For example, a 2-year study conducted by the Microbiology Department of Dr. Ram Manohar Lohia Hospital and PGIMER, New Delhi, in infants < 1 year of age with suspected UTI registered 50% of the Gram-negative isolates (E. coli was the predominant isolate) to be highly resistant to a panel of antimicrobial therapies, including gentamicin, amikacin, cefotaxime and norfloxacin. Interestingly, nitrofurantoin (oral therapy) and piperacillintazobactam (parental therapy) were found to have least level of resistance at 5%.³⁷Kaur N, Sharma S, Malhotra S, et al. Urinary Tract Infection: Aetiology and Antimicrobial Resistance Pattern in Infants From A Tertiary Care Hospital in Northern India. Journal of Clinical and Diagnostic Research. 2014;8(10):DC01-DC03.   In the same manner, a study conducted by National Salmonella and Escherichia Centre, Kasauli, Himachal Pradesh, which evaluated E. coli isolated from UTI patients during 2007- 2008 for antibiogram, plasmid transferability and stability of resistance markers, registered 90.9% of the isolates to be sensitive to nitrofurantoin whereas the highest level of resistance was noted to nalidixic acid; table 6 shows the objective findings.³⁸Kumar Y, Sood S, Sharma A, et al. Antibiogram and characterization of resistance markers among Escherichia coli Isolates from urinary tract infections. J Infect Dev Ctries. 2013;7(7):513-519.

In Eastern region of India too, antibiotic resistance patterns in uropathogens which are in agreement with the patterns in the other regions of India have been documented. Sharan et al assessed these patterns in childhood UTI cases in Jamshedpur, India, and found E. coli to be the leading isolate. They noted these isolates to be highly susceptible, in the descending order, to nitrofurantoin, levofloxacin, ofloxacin and azithromycin, and significantly resistant to penicillin and cephalosporins.³⁹Sharan R, Kumar D, Mukherjee. Bacteriology and Antibiotic Resistance Pattern in Community Acquired Urinary Tract Infection. Indian Pediatr. 2013;50:707.

References

1. Vasudevan R. Urinary Tract Infection: An Overview of the Infection and the Associated Risk Factors. J Microbiol Exp. 2014;1(2):00008.
2. Rowe TA, Juthani-Mehta M. Diagnosis and Management of Urinary Tract Infection in Older Adults. Infect Dis Clin North Am. 2014;28(1):75-89.
3. Beyene G, Tsegaye W. Bacterial Uropathogens in Urinary Tract Infection and Antibiotic Susceptibility Pattern in Jimma University Specialized Hospital, Southwest Ethiopia. Ethiop J Health Sci. 2011;21(2):141-146.
4. Sharma I, Paul D. Prevalence of community acquired urinary tract infections in Silchar Medical College, Assam, India and its antimicrobial susceptibility profile. Indian Journal of Medical Sciences. 2012;66(11):273-279.
5. Flores-Mireles AL, Walker JN, Caparon M, et al. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol. 2015;13(5):269-84.
6. Hsueh PR, Hoban DJ, Carmeli Y, et al. Consensus review of the epidemiology and appropriate antimicrobial therapy of complicated urinary tract infections in Asia-Pacific region. J Infect. 2011 Aug;63(2):114-23.
7. Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Dis Mon. 2003 Feb;49(2):53-70.
8. 8. Sumati AH, Saritha NK. Association of Urinary Tract Infection in Women with Bacterial Vaginosis. J Glob Infect Dis. 2009;1(2):151-152.
9. Prakash D, Saxena RS. Distribution and Antimicrobial Susceptibility Pattern of Bacterial Pathogens Causing Urinary Tract Infection in Urban Community of Meerut City, India. ISRN Microbiology. 2013;Volume 2013:Article ID 749629.
10. Harrington RD, Hooton TM. Urinary tract infection risk factors and gender. J Gend Specif Med. 2000 Nov-Dec;3(8):27-34.
11. Al-Badr A, Al-Shaikh G. Recurrent Urinary Tract Infections Management in Women A review. Sultan Qaboos Univ Med J. 2013;13(3):359-367.
12. Beveridge LA, Davey PG, Phillips G, et al. Optimal management of urinary tract infections in older people. Clin Interv Aging. 2011; 6: 173-180.
13. Ma JF, Shortliffe LM. Urinary tract infection in children: etiology and epidemiology. Urol Clin North Am. 2004;31(3):517-26, ix-x.
14. Nickavar A, Sotoudeh K. Treatment and Prophylaxis in Pediatric Urinary Tract Infection. Int J Prev Med. 2011;2(1):4-9.
15. Lo DS, Shieh HH, Betta Ragazzi SP, et al. Community-acquired urinary tract infection: age and gender-dependent etiology. J Bras Nefrol. 2013;35(2):93-98.
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