|Year : 2018 | Volume
| Issue : 3 | Page : 93-99
Antimicrobial resistance patterns in a tertiary care nephro-urology center in South India
Sundaramoorthy Vijayganapathy1, Vilvapathy Senguttuvan Karthikeyan1, Ashwin Mallya1, Kuthagale Muddegowda Mythri2, Ramahanumaiah Viswanatha1, Ramaiah Keshavamurthy1
1 Department of Urology, Institute of Nephro Urology, Victoria Hospital Campus, Bengaluru, Karnataka, India
2 Department of Microbiology, Institute of Nephro Urology, Victoria Hospital Campus, Bengaluru, Karnataka, India
|Date of Web Publication||17-Dec-2018|
Department of Urology, Institute of Nephro Urology, Victoria Hospital Campus, Bengaluru - 560 002, Karnataka
Source of Support: None, Conflict of Interest: None
Background and Objective: Urinary tract infections lead to increased hospitalization, direct patient costs, and mortality. Data on the prevalence of common uropathogens and antimicrobial (AM) susceptibility pattern are sparse and it varies geographically. Our aim was to determine AM resistance patterns in a tertiary urological center. Materials and Methods: Data on bacterial uropathogens and AM susceptibility between January 2015 and January 2016 in 1080 significant bacterial isolates were analyzed. Results: The most commonly isolated bacteria were Escherichia coli in 720 (66.6%), Klebsiella species in 170 (15.7%), and Pseudomonas aeruginosa in 80 (7.4%) patients. E. coli from inpatients was susceptible to imipenem (260; 97%), amikacin (212; 79%), piperacillin–tazobactam (206; 77%), nitrofurantoin (198; 73%), and cefoperazone–sulbactam (206; 77%). Klebsiella isolates were sensitive only to imipenem, piperacillin–tazobactam, and cefoperazone–sulbactam. Pseudomonas and Proteus species were sensitive only to imipenem and piperacillin–tazobactam. In outpatients, the common uropathogens showed lesser resistance only to nitrofurantoin (15%–47%). Conclusions: E. coli and Klebsiella are the most common uropathogens. Nitrofurantoin should be the drug of choice in outpatients. In inpatients, beta-lactamase inhibitors and amikacin have good AM sensitivity. Carbapenems should be the first choice AM agents in the intensive care unit.
Keywords: Antimicrobial policy, antimicrobial resistance, urinary tract infections, uropathogens
|How to cite this article:|
Vijayganapathy S, Karthikeyan VS, Mallya A, Mythri KM, Viswanatha R, Keshavamurthy R. Antimicrobial resistance patterns in a tertiary care nephro-urology center in South India. J Integr Nephrol Androl 2018;5:93-9
|How to cite this URL:|
Vijayganapathy S, Karthikeyan VS, Mallya A, Mythri KM, Viswanatha R, Keshavamurthy R. Antimicrobial resistance patterns in a tertiary care nephro-urology center in South India. J Integr Nephrol Androl [serial online] 2018 [cited 2020 Jan 25];5:93-9. Available from: http://www.journal-ina.com/text.asp?2018/5/3/93/247692
| Introduction|| |
Urinary tract infections (UTIs) are the second most common after respiratory infections. UTI poses a significant health problem in the community as well as in the hospitals., UTIs represent at least 40% of all hospital-acquired infections (HAI) and are mostly catheter-associated UTI (CAUTI)., There are more than 1 million CAUTIs per year in the United States, and up to 40% of hospital Gram-negative bacteremia per year originate as UTI in hospitalized patients., According to the Global Prevalence of Infections in Urology studies, 10%–12% of patients hospitalized in urological wards have HAI, which are more resistant to usual antimicrobials (AMs)., The estimated annual cost of CAUTI in the United States is significant ($1.6 billion).,, UTI accounts for nearly 7 million office visits and 1 million emergency department visits, resulting in 100,000 hospitalizations per year.,, Selection of the appropriate AM for UTI requires thoughtful consideration of direct medical costs and AM resistance patterns, both of which increase with the irrational use of AM. The distribution of uropathogens and their susceptibility pattern to AM vary regionally and may spread across geographic areas due to the exchange of genetic material to the susceptible microbes., Hence, an up to date knowledge of the causative microorganisms and their AM susceptibility are necessary to cope with the spreading resistance to AM. This study assessed the current distribution of uropathogens at a tertiary care referral urological center in South India and their AM resistance pattern. This will aid in formulating drug of choice in patients with UTI in outpatients, patients needing inpatient care, and those presenting with urosepsis.
| Materials and Methods|| |
We analyzed the urine culture and AM sensitivity data from January 2015 to January 2016 at our institute. Institute research board approval was taken. It included pediatric and adult patients. Midstream/catheter (perurethral/suprapubic) urine samples as appropriate were collected in sterile containers. These samples were inoculated on blood agar and MacConkey medium plates with a standard tungsten wire loop within 1 h. They were incubated at 37°C for 24–48 h, and ≥ 105 colony-forming units/mL was considered as significant bacteriuria. Standard biochemical tests were performed on the colonies for final identification of the isolate. AM susceptibility was done by Kirby–Bauer disc diffusion method on Mueller–Hinton agar, and the interpretations were carried out in accordance with the Clinical and Laboratory Standards Institute guidelines. Susceptibility was tested to gentamicin (G), amikacin (Ak), piperacillin–tazobactam (Pz), cefuroxime (Cf), cefotaxime (Cfo), ceftazidime (Cfz), cefoperazone–sulbactam (Cfs), cefepime (Cp), imipenem (I), trimethoprim–sulfamethoxazole (Tz), ciprofloxacin (C), levofloxacin (L), doxycycline (D), and nitrofurantoin (N). Among inpatients and intensive care unit (ICU) patients with UTI, only those with features of systemic inflammatory response syndrome (SIRS) and urine culture showing significant bacterial growth were included for analysis. Patients with catheter colonization who did not have features of SIRS and screening samples for UTI in pregnant patients were excluded from the study. We classified the patients into three groups – UTI treated on outpatient basis (outpatient department [OPD]), UTI needing inpatient care (inpatient department [IPD]), and those presenting with urosepsis requiring ICU admission. These groups were further classified for oral or parenteral AM for the OPD and IPD patients, respectively. Statistical analysis was done using SPSS version 20 (IBM Corporation, Armonk, New York, USA), and Chi-square test was used to compare differences in proportions across subgroups.
| Results|| |
A total of 1806 urine specimens were processed for culture and AM sensitivity during the study period. A majority of the samples were from females (1264/1806; 70%). Out of these, 1080 (59.8%) grew pathogenic organisms with a male: female ratio of 454:626 (1:1.3). The median (interquartile range) age was 60 (24) years. The most common organisms cultured were Escherichia More Details coli (720/1080; 66.7%) and Klebsiella species (170/1080; 15.7%). Pseudomonas aeruginosa contributed to 7.4% (80/1080), and the distribution of other organisms is shown in [Table 1]. The AM resistance patterns for UTI patients treated in the OPD and IPD have been shown in [Figure 1] and [Figure 2], respectively. The AM resistance patterns for UTI requiring ICU care is shown in [Figure 3].
|Figure 1: Antimicrobial resistance in urinary tract infection treated in outpatient department (n = 578 patients). Gentamicin (G), amikacin (Ak), piperacillin–tazobactam (Pz), cefuroxime (Cf), cefotaxime (Cfo), ceftazidime (Cfz), cefoperazone–sulbactam (Cfs), cefepime (Cp), imipenem (I), trimethoprim–sulfamethoxazole (Tz), ciprofloxacin (C), levofloxacin (L), doxycycline (D), and nitrofurantoin (N)|
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|Figure 2: Antimicrobial resistance in urinary tract infection requiring inpatient care (n = 422 patients). Gentamicin (G), amikacin (Ak), piperacillin–tazobactam (Pz), cefuroxime (Cf), cefotaxime (Cfo), ceftazidime (Cfz), cefoperazone–sulbactam (Cfs), cefepime (Cp), imipenem (I), trimethoprim–sulfamethoxazole (Tz), ciprofloxacin (C), levofloxacin (L), doxycycline (D), and nitrofurantoin (N)|
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|Figure 3: Antimicrobial resistance in urosepsis patients needing intensive care unit care (n = 80 patients). Gentamicin (G), amikacin (Ak), piperacillin–tazobactam (Pz), cefuroxime (Cf), cefotaxime (Cfo), ceftazidime (Cfz), cefoperazone–sulbactam (Cfs), cefepime (Cp), imipenem (I), trimethoprim–sulfamethoxazole (Tz), ciprofloxacin (C), levofloxacin (L), doxycycline (D), and nitrofurantoin (N)|
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Outpatient department urinary tract infection
Among the microbes causing UTI in OPD patients (OPD UTI), resistance to commonly administered oral AM such as fluoroquinolones (FQs), trimethoprim–sulfamethoxazole, and cefuroxime was very high (>75%). AM resistance to nitrofurantoin was the least. OPD UTI patients had significant resistance to parenteral AM [Figure 1]. The OPD UTI with parenteral drug resistance showed a similar pattern to UTI needing inpatient care [Figure 1] and [Figure 2].
Inpatient department urinary tract infection and urinary tract infection needing intensive care unit care
Among the IPD UTI, there was a significant resistance to commonly used third-generation cephalosporins. Strains showed least AM resistance to carbapenems, amikacin, piperacillin–tazobactam, and cefoperazone–sulbactam [Figure 2]. Among the UTI needing ICU care due to urosepsis, the AM resistance was least for the carbapenems [Figure 3].
Extended-spectrum beta-lactamase-producing organisms
Organisms were uniformly resistant to common first-line drugs such as cephalosporins. Addition of a beta-lactamase inhibitor (tazobactam to piperacillin or sulbactam to cefoperazone) improved the susceptibility of uropathogens. This highlights the significance of extended-spectrum beta-lactamase (ESBL)-producing microbes in these sick patients. ESBL is constituted by organisms resistant to third-generation cephalosporins such as ceftriaxone, cefotaxime, and cefoperazone.,,, These ESBL constituted 75.7% in our study and the strains were sensitive to carbapenems, piperacillin–tazobactam, and cefoperazone–sulbactam. The organisms had a 3% resistance to imipenem and 41%, 29.5%, and 30.3% resistance to amikacin, piperacillin–tazobactam, and cefoperazone–sulbactam, respectively.
Comparison of outpatient department, inpatient department, and intensive care unit urinary tract infection
We observed that in the OPD, isolates with E. coli had the least resistance to nitrofurantoin (15%) while Klebsiella had a higher resistance to nitrofurantoin (40%). Other microbes were resistant to oral AM agents [Figure 1]. Among parenteral AM, the AM resistance patterns were similar to IPD. In IPD and OPD with sensitive strains, parenteral AM patients had maximum AM resistance to commonly used third-generation cephalosporins such as ceftriaxone, cefotaxime, and ceftazidime (77%–81%) and gentamicin (39%–84%). P. aeruginosa had least resistance to imipenem (2%), amikacin, and piperacillin–tazobactam (25%). AM agents containing lactamase inhibitors had a lower resistance among OPD (20%–34%) and IPD (23%–34%) strains. These agents had efficacy against most microbes causing OPD and IPD UTI [Figure 1] and [Figure 2]. Among ICU strains, there was a slightly higher resistance to lactamase inhibitors (25%–36%) and amikacin (30%–52%) than IPD UTI, but this was not statistically significant. E. coli and Klebsiella had least AM resistance to imipenem (1%–3%) while P. aeruginosa had 6% AM resistance to imipenem [Figure 3]. Strains had a uniformly high resistance (60%–74%) to cefepime across all patient population [Figure 1], [Figure 2], [Figure 3] (P > 0.05). The resistance patterns of amikacin (P = 0.013) and nitrofurantoin (P = 0.03) for E. coli and for amikacin (P < 0.001) for Klebsiella species were statistically significantly different between subgroups. The resistance of nitrofurantoin was statistically significantly different among the three organisms, i. e., E. coli, Klebsiella, and P. aeruginosa (P = 0.007). The AM resistance patterns of other drugs across subgroups and AM across different susceptible organisms were similar (P > 0.05).
Among ICU isolates, multidrug resistance was observed in 3 (7.5%) among E. coli, 2 (12.5%) Klebsiella species and 2 (12.5%) P. aeruginosa. All these organisms were sensitive only to colistin. Two (25%) patients had Enterococcus were sensitive to vancomycin and linezolid. Among IPD isolates, multidrug resistance was observed in 12 (4.4%) E. coli, 9 (10.7%) Klebsiella species, 2 (8.3%) P. aeruginosa and 3 (12.5%) Citrobacter species and all isolates were sensitive only to colistin. Two (10%) patients had Enterococcus were sensitive only to vancomycin and linezolid. Among OPD isolates, multidrug resistance was observed in 10 (2.4%) E. coli, 3 (4.3%) Klebsiella species, 2 (5%) P. aeruginosa, 2 (7.7%) Citrobacter and 1 (5%) Enterobacter and all isolates were sensitive only to imipenem. Two (16.7%) patients had Proteus species isolated and it was sensitive only to vancomycin and linezolid.
| Discussion|| |
According to our study, 66.7% (720/1080) of patients had at least one uropathogen isolated. E. coli was the most common (720/1080; 66.7%) uropathogen. The prevalence of E. coli in other studies ranges from 48% to 65%., E. coli was the most common organism in all the three groups (OPD, IPD, and ICU) of patients. Klebsiella was the second most common (15.7%) microbe and this is similar to other reports (8%–26%).
Microbes causing UTI in outpatients had a high prevalence of resistance to oral AM such as ciprofloxacin, levofloxacin, doxycycline, cefuroxime, and trimethoprim–sulfamethoxazole which are routinely used in OPD practice in as much as 65%–80% of patients. Nitrofurantoin resistance was lowest at 23%. A major proportion of the OPD UTI had very high resistance to parenteral AM (80%). This was possibly due to the fact that ours is a tertiary care referral center. Patients were initiated on multiple parenteral AM in other centers before referral. This reflects the trend of AM usage and also partly the high proportion of resistance of strains to parenteral AM as seen in the other urological centers as well.
We compared our AM resistance patterns with the recent Indian literature [Table 2].,, There is no report of nitrofurantoin resistance in these studies. This might be due to the recent trend of increased nitrofurantoin usage in UTI. It is alarming to note that Klebsiella species already have 40% resistance to this drug. In our study, we observed a fairly high degree of resistance (65%–80%) to cefotaxime, ceftriaxone, and ceftazidime. This suggests recent onset of resistance to these drugs as these reports were from 2007 to 2011.,, This is important because all inpatients with UTI are empirically started on third-generation cephalosporins which had up to 71% resistance. Even ceftazidime, an antipseudomonal AM, had up to 68% resistance in our study. This is constantly increasing over the years. We noted similar lower AM resistance patterns for amikacin (21%–52%), lactamase inhibitors (23%–36%), and carbapenems (1%–6%), and these should be considered as first-line agents in IPD and ICU UTI.
Resistance to oral AMs such as levofloxacin, ciprofloxacin, trimethoprim–sulfamethoxazole, and doxycycline is rampant, and the usage of these AMs in community-acquired UTI is questionable as first-line agents. As observed from our study, nitrofurantoin appears to be the first-choice agent in Community acquired urinary tract infection. However, due to its unique properties, emergence of nitrofurantoin resistance is lesser.,, We report a 40% incidence of nitrofurantoin resistance in Klebsiella which contributes to around 15% of OPD UTI., Thus, presumptive oral AM administration in OPD UTI requires further evaluation and AM policy, culture and AM sensitivity testing for CAI, and follow-up cultures to assess efficacy.
In the ICU, carbapenems had the least AM resistance (1%–6%) according to our data. In fact, we report lower resistance levels to imipenem (2%) compared to the Indian literature (15%–18%). We observed high resistance to cephalosporins due to ESBL-producing microbes. We further observed that addition of lactamase inhibitor improved AM susceptibility of ICU uropathogens.
We identified that E. coli had 76% resistance to trimethoprim–sulfamethoxazole in our study. In an earlier report from South India by Manjunath et al., they reported a lower resistance to trimethoprim–sulfamethoxazole. This was attributed to paucity of government supplies to trimethoprim–sulfamethoxazole and lesser access to this AM agent. However, the latest study shows a high degree of AM resistance to trimethoprim–sulfamethoxazole which depicts the trend of its usage in UTI. There is widespread resistance to FQ which are the first-line empirical agents for UTI in India. FQ resistance has been reported worldwide.,,,,
In a recent report (2016) from Kolkata, the most common organisms isolated were E. coli (59.6%), Enterococcus species (14.9%), and Klebsiella species (10.6%). In catheterized patients, E. coli (64%) and Klebsiella species (12%) were more common than Enterococcus (10%). They had good in vitro susceptibility to aminoglycosides, cefoperazone–sulbactam, and nitrofurantoin. Enterobacter, Citrobacter, Morganella, and Pseudomonas species were sensitive to higher antibiotics such as carbapenems and polymyxin B. Staphylococcus aureus was susceptible to linezolid and vancomycin.
Our study had a few limitations. OPD patients had significant bias due to referral from other hospital where injectable AMs are used. This may not represent the true prevalence of uropathogens and AM resistance patterns in the community. This study has not assessed the clinical response to sensitive AM. The next step would be to annually update AM policies by acquiring AM resistance pattern in the first quarter of the year and applying it to the rest of the year and to study the change in resistance pattern over the years.
| Conclusions|| |
E. coli and Klebsiella species are the most common uropathogens. In outpatients, the common bacterial strains show the least resistance to nitrofurantoin. In UTI patients needing inpatient care, addition of a beta-lactamase inhibitor and amikacin is a frontline option. In urosepsis patients, carbapenems should be the first-choice agents. A strict escalation and de-escalation principle should be adopted on the basis of AM sensitivity analysis to curb the emergence of resistance strains.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Abejew AA, Denboba AA, Mekonnen AG. Prevalence and antibiotic resistance pattern of urinary tract bacterial infections in Dessie area, North-East Ethiopia. BMC Res Notes 2014;7:687.
Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 8th
ed. New York: McGraw-Hill; 2011.
Shoskes D. Urinary tract infections. In: the American Urological Association Educational Review Manual in Urology. 3rd
ed., Ch. 23. Castle Connolly Graduate Medical Publishing, Ltd; 2011. p. 737-66.
Wagenlehner F, Tandogdu Z, Bartoletti R, Cai T, Cek M, Kulchavenya E, et al.
The global prevalence of infections in urology study: A Long-term, worldwide surveillance study on urological infections. Pathogens 2016;5. pii: E10.
Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, et al.
Multistate point-prevalence survey of health care-associated infections. N Engl J Med 2014;370:1198-208.
Zarb P, Coignard B, Griskeviciene J, Muller A, Vankerckhoven V, Weist K, et al.
The European centre for disease prevention and control (ECDC) pilot point prevalence survey of healthcare-associated infections and antimicrobial use. Euro Surveill 2012;17. pii: 20316.
Bjerklund Johansen TE, Cek M, Naber K, Stratchounski L, Svendsen MV, Tenke P, et al.
Prevalence of hospital-acquired urinary tract infections in urology departments. Eur Urol 2007;51:1100-11.
Bendall MJ. A review of urinary tract infection in the elderly. J Antimicrob Chemother 1984;13 Suppl B: 69-78.
Brown P, Ki M, Foxman B. Acute pyelonephritis among adults: Cost of illness and considerations for the economic evaluation of therapy. Pharmacoeconomics 2005;23:1123-42.
Foxman B. Urinary tract infection syndromes: Occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect Dis Clin North Am 2014;28:1-13.
Stamm WE, Norrby SR. Urinary tract infections: Disease panorama and challenges. J Infect Dis 2001;183 Suppl 1:S1-4.
Somashekara SC, Deepalaxmi S, Jagannath N, Ramesh B, Laveesh MR, Govindadas D, et al.
Retrospective analysis of antibiotic resistance pattern to urinary pathogens in a tertiary care hospital in South India. J Basic Clin Pharm 2014;5:105-8.
Hasan AS, Nair D, Kaur J, Baweja G, Deb M, Aggarwal P, et al.
Resistance patterns of urinary isolates in a tertiary Indian hospital. J Ayub Med Coll Abbottabad 2007;19:39-41.
CLSI. Performance Standards For Antimicrobial Disk Susceptibility Tests; Approved standard – Twelfth Edition. CLSI document M02-A12. Wayne, PA: Clinical and Laboratory Standards Institute; 2015.
Rawat D, Nair D. Extended-spectrum β-lactamases in gram negative bacteria. J Glob Infect Dis 2010;2:263-74.
Paterson DL, Bonomo RA. Extended-spectrum beta-lactamases: A clinical update. Clin Microbiol Rev 2005;18:657-86.
Pitout JD, Nordmann P, Laupland KB, Poirel L. Emergence of Enterobacteriaceae
producing extended-spectrum beta-lactamases (ESBLs) in the community. J Antimicrob Chemother 2005;56:52-9.
Farrell DJ, Morrissey I, De Rubeis D, Robbins M, Felmingham D. A UK multicentre study of the antimicrobial susceptibility of bacterial pathogens causing urinary tract infection. J Infect 2003;46:94-100.
Krishna S, Pushpalatha H, Srihari N, Nagabhushan S, Divya P. Increasing resistance patterns of pathogenic bacteria causing urinary tract infections at a tertiary care hospital. Int J Pharm Biomed Res 2013;4:105-7.
Mandal J, Acharya NS, Buddhapriya D, Parija SC. Antibiotic resistance pattern among common bacterial uropathogens with a special reference to ciprofloxacin resistant Escherichia coli
. Indian J Med Res 2012;136:842-9.
] [Full text]
Paterson DL. Recommendation for treatment of severe infections caused by Enterobacteriaceae
producing extended-spectrum beta-lactamases (ESBLs). Clin Microbiol Infect 2000;6:460-3.
Gupta N, Kundra S, Sharma A, Gautam V, Arora DR. Antimicrobial susceptibility of uropathogens in India. J Infect Dis Antimicrob Agents 2007;24:13-8.
Manjunath GN, Prakash R, Vamseedhar Annam KS. Changing trends in the spectrum of antimicrobial drug resistance pattern of uropathogens isolated from hospitals and community patients with urinary tract infections in Tumkur and Bangalore. Int J Biol Med Res 2011;2:504-7.
Murugan K, Savitha T, Vasanthi S. Retrospective study of antibiotic resistance among uropathogens from rural teaching hospital, Tamilnadu, India. Asian Pac J Trop Dis 2012;2:375-80.
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;21:141-6.
Moyo SJ, Aboud S, Kasubi M, Maselle SY. Bacterial isolates and drug susceptibility patterns of urinary tract infection among pregnant women at Muhimbili national hospital in Tanzania. Tanzan J Health Res 2010;12:236-40.
Fluit AC, Jones ME, Schmitz FJ, Acar J, Gupta R, Verhoef J, et al.
Antimicrobial resistance among urinary tract infection (UTI) isolates in Europe: Results from the SENTRY antimicrobial surveillance program 1997. Antonie Van Leeuwenhoek 2000;77:147-52.
Chatterjee N, Chatterjee C, Ghosh S, Mukhopadhyay M, Brahmachari R, Patar K, et al.
Pattern of urinary antibiograms in a tertiary care hospital of Eastern India. J Assoc Physicians India 2016;64:26-30.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]