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Spectrum of antimicrobial susceptibility pattern of pathogens isolated from patients with urinary tract infections in tertiary care hospital in Hadoti Region of Rajasthan.

INTRODUCTION

UTI remains one of the most common bacterial infections and second most common infectious disease in the community practice. Approximately, about 150 million people were diagnosed with UTI each year. In present scenario, the essence of antimicrobial drug resistance of major uropathogens has posed a global threat. [1] Of the various uropathogens, the most common organisms are E. Coli, Enterococcus fecalis, Staphylococcus aureus, Enterococci SPP and Klebsiella SPP. [13] But most of these organisms have developed resistance to antimicrobial agents like cotrimoxazole, ampicillin, amoxicillin, nitrofurantoin. [2-5] piperacillin, nalidixic acid. [2,6] erythromycin, chloramphenicol. [3] Fluoroquinolones. [7,8] tetracyclines, carbenicillin. [9] and 3rd generation cephalosporins. [10] Inappropriate and empirical usage of wide spectrum antibiotics, insufficient hygiene, immunesuppression and prolonged hospitalization are some of the major aetiological factors that elevate the chances of infection. [2,3] The use of low standard antimicrobials further adds to the emerging drug resistance, which could turn to be one of the biggest factor for mortality in developing and underdeveloped countries. [1] There were many studies conducted in the past in different geographical regions of the world to assess the antimicrobial resistance in uropathogens. Most of the studies disclosed the augment of antimicrobial resistance to a panicking situation.

Many studies also exposed the common uropathogens that caused UTI and also the gender that was more vulnerable. The commonest infecting organism and pattern of resistance keep changing overtime. Hence, the present study was performed to identify the changing etiologic trends of UTI and the antimicrobial resistance.

MATERIALS AND METHOD

This was a retrospective study, which used laboratory report sheets of urine culture results and antibiograms carried out in Laboratory.

A total number of 6350 samples were reviewed in this study, from May 2010 to June 2015. This study assessed resistance in a total number of 30 antimicrobials (Table 1). All culture positive samples report from community acquired as well as nosocomial UTI was considered. Infection reports belonging to all the age group and both the sex were reviewed during the study. In the study, patients were divided into four different age groups, i.e. NB (NewBorn)-19 years, 20-49 years, 50-79 years and patients who aged more than 80 years old. The study assessed the following variables from the record sheets, which were analysed and recorded for study purpose: age and sex of patients, microbial species (As recorded in urine culture reports) and drug resistance as recorded in antibiograms forms.

RESULTS

The study analysed 6350 samples of positive urinary tract infection record sheets in a period of five year and one month. The recorded data sheets included reports from those of newborn up to geriatrics.

About 12 species of micro-organisms were identified that offered resistance to different antimicrobials in different pattern. E. coli (59.2%) topped the charts among the most commonly identified uropathogens followed by Klebsiella SPP (12.1%), Enterococcus SPP (10.1%) and Pseudomonas SPP (9.3%). (Table 2).

The specific antimicrobial resistance pattern was assessed in the most common uropathogens, in top ten antimicrobials that showed highest resistance. The antimicrobial resistance spectrum assessment revealed that 80.4% of the identified organisms were resistant towards ampicillin, 73% against ciprofloxacin and 70.4% towards amoxicillin. The study showed 40%-53% of the identified organisms was resistant against norfloxacin, cephalexin, cotrimoxazole, cefuroxime, ceftazidime, ceftriaxone and gentamicin. A detailed insight of antimicrobial resistance pattern has been illustrated in Table (3).

E. coli was the most common aetiological agent of UTI in the study. E. coli was highly resistant towards ampicillin (91%) followed by amoxicillin (84%). The most commonly identified uropathogens chiefly belonged to the family of Enterobacteriaceae (E. coli, Klebsiella SPP and Enterococcus SPP) and Pseudomonaceae (Pseudomonas SPP) (Table 4, 3). The resistance pattern of these organisms from different families differed from one class of drugs to another, i.e. the organisms that belonged to Enterobacteriaceae family showed predominant resistance against Penicillins (amoxicillin, ampicillin), Fluoroquinolones (ciprofloxacin, norfloxacin), Aminoglycosides (gentamicin) and Cephalosporins (cephalexin, cefuroxime, Ceftriaxone and ceftazidime). The resistance of the organisms from Enterobacteriaceae family varied from 42%-98%, except Enterococcus SPP which had offered relatively less resistance to all other class of drugs except Fluoroquinolones (ciprofloxacin 90%) (Table 4, 3). As mentioned before, ten antimicrobials were identified in this study that tendered resistance from 12 different species of uropathogens. The antimicrobial resistance ranged anywhere from 42% to 98%. Some antimicrobials like Novobiocin, Doxycycline, Linezolid and Furomycin showed least or considerably negligible resistance of 0.1% to different uropathogens. (Table 4.)

As cited before 6350 samples were assessed with Male: Female ratio being 1.4:1 (Table 6), showing high vulnerability of females towards UTI.

In this study UTI was more prevalent in the age group of 50-79 years and E. coli was the most commonly isolated uropathogen irrespective of age groups. (Table 7)

DISCUSSION

Constant survey of antimicrobial resistance plays a very important role in the empiric treatment of UTI. In a healthcare setting, a very little extraventure on antimicrobial resistance survey can facilitate to accrue extremely practical information of the resistance pattern. Ampicillin, amoxicillin, ciprofloxacin, norfloxacin, cephalexin were some of the antimicrobials that bade heavy resistance from organisms that belonged to Enterobacteriaceae family. While Pseudomonas SPP offered heavy resistance against Ofloxacin, imipenem, netilmicin, etc. Among the 12 species of uropathogens that were identified in the study, E. coli (59.3%) emerged as the most predominant organism followed by Klebsiella SPP (12.3%), which is in par with similar studies.[3,4,10] The study also revealed that females (60.5%) were more susceptible to UTI than males, which is also similar to other studies. [1,10,11] The age wise data was analysed in order to assess the frequency of UTI in different age groups. This study portrayed that aged people, i.e. 50-79 years were more prone to UTI than any other groups. This result is in comparison with other studies. [1,12,13]

Antimicrobial resistance offered by different uropathogens is one of the barricades that might hinder a successful treatment. Antimicrobial resistance pattern varies with time which might increase or decrease. [9]

This study also indicated the different pattern of antimicrobial resistance in different families of uropathogen, i.e. Enterobacteriaceae family and Pseudomonaceae family. E. coli identified in this study were highly resistant to ampicillin (<90%) and amoxicillin (<80%). E. coli offered almost equal resistance towards ciprofloxacin and norfloxacin (75% and 74%), cephalosporins (56%-62%), while Klebsiella SPP were comparatively less resistant to these antimicrobials (ciprofloxacin and norfloxacin), i.e. 37% and 34%. Studies that were conducted in India showed that the isolates of E. coli showed high resistance towards Ampicillin and amoxicillin which was in agreement with this study [1,3,7,14] but did show that ciprofloxacin resistance is escalating. [15]

The Klebsiella SPP was exceedingly resistant to ampicillin (98%) followed by amoxicillin (90%), which showed highest resistance to any particular drug in this retrospective survey. This high resistance to ampicillin and amoxicillin by Klebsiella SPP was seen in many other studies [1,2,10,6]

Pseudomonas SPP showed a different pattern of resistance than that of Enterobacteriaceae. Pseudomonas SPP were more resistant to antimicrobials like amikacin (65.6%), netilmycin, ciprofloxacin (85%), Ofloxacin (81%), Aztreonam (55%), carbenicillin (69.3%), imipenem (72%).

This study had come across a few cases of ESBL (Extended Spectrum Beta Lactamases) producing E. coli, which showed high resistance mainly against cephalosporins. These cephalosporins are extensively used in all healthcare sectors for treatment of infections. These ESBL producers mainly belonged to the Klebsiella SPP, when it was first discovered in the mid 1980's, but now the most causal organism of UTI, E. coli has picked up the trend of synthesizing ESBL, which is increasing in number. This increasing ESBL producing E. coli have also developed resistance against penicillins as well!17! These ESBL producing E. coli has made treatment difficult and costlier. These organisms have shown high resistance towards ciprofloxacin (76.5%) and cotrimoxazole (74.4%) and susceptible towards amikacin and fosfomycin [18]

CONCLUSION

This retrospective study furnished much needed information on the common uropathogens and their drug resistance pattern. This study is clear that E. coli is on a ramp age, causing most cases of UTI. Antimicrobials like ampicillin and amoxicillin have developed resistance to such a level that, prescribing them would definitely lead to treatment failure. Development of resistance against penicillins and cotrimoxazole can be predictable, which might be due to widespread use. But the matter of concern is resistance has also affected the use of Fluoroquinolones (Ciprofloxacin and norfloxacin) and cephalosporins. Aminoglycosides were in use for quite a long period in the history of infectious diseases. They have not considerably developed much resistance against all uropathogens but for Pseudomonas SPP.

Females and geriatrics populations are more vulnerable to UTI when compared to males and other age groups. Females are more prone to UTI because of their characteristic anatomy and physiological changes while geriatrics populations might be because of their suppressed immunity.

The Indian scenario is something different than the scenario in the west. Uropathogens show increased resistance; hence, it is necessary to diagnose clinically followed by sensitivity testing, as direct empiric treatment might lead to treatment failure. UTI guidelines can only be developed after thorough surveillance of drug resistance in the Indian subcontinent. UTI and other infectious diseases are to be considered dangerous due to global escalation of drug resistance pattern.

REFERENCES

[1.] Akram M, Shahid M, Khan AU. Etiology and Antibiotic Resistance Patterns of Community-acquired Urinary Tract Infections in JNMC Hospital Aligarh, India. Ann Clin Microbiol Antimicrob. 2007;6:4.

[2.] Sweih NA, Jamaal Wand Rotimi VO. Spectrum and antibiotic resistance of uropathogens isolated from hospital and community patients with urinary tract infections in two large hospitals in Kuwait. Med Princ Pract. 2005;14:401-407.

[3.] Khan A, Uand Zaman MS. Multiple drug resistance pattern in urinary tract infection patients in Aligarh. Biomedical Research. 2006;17(3):179-181.

[4.] DeFrancesco MA, Ravizzola G, Peroni L, et al. Urinary tract infections in Brescia, Italy: Etiology of Uropathogens and Antimicrobial Resistance of Common Uropathogens. Med Sci Monit. 2007;13(6):136-144.

[5.] Shigemura K, Arakawa S, Tanaka K, et al. Clinical investigation of isolated bacteria from urinary tracts of hospitalized patients and their susceptibilities to antibiotics. J Infect Chemother. 2009;15:18-22.

[6.] Hryniewicz K, Szczypa K, Sulikowska A, Jankowski K, Betlejewska K, Hryniewicz W. Antibiotic susceptibility of bacterial strains isolated from urinary tract infections in Poland. J Antimicrob Chemother. 2001;47:773-780.

[7.] Kothari A and Sagar V. Antibiotic resistance in pathogens causing community-acquired urinary tract infections in India: A Multicenter Study. J Infect Developing Countries. 2008;2(5):354-358.

[8.] Wagenlehner FME, Niemetz A, Dalhoff A, et al. Spectrum and antibiotic resistance of uropathogens from hospitalized patients with urinary tract infections: 1994-2000. Int J Antimicrob Agents 2002;19:557-564.

[9.] Dyer IE, Sankary IM, Dawson JO. Antibiotic resistance in bacterial urinary tract infections, 1991 to 1997. WJM 1998;169(5):265-268.

[10.] Dimitrov ES, Udo EE, Emara M, et al. Etiology and antibiotic susceptibility patterns of community- acquired urinary tract infections in a Kuwait Hospital. Med Princ Pract. 2004;13:334-339.

[11.] Dash N, Al-Zarouni, Al-Kous, Al-ShehhiF, Al-NajjarJ, Senok A, et al. Distribution and resistance trends of community associated urinary tract pathogens in Sharjah, UAE. Microbiology Insights. 2008;1:41-45.

[12.] Goettsch W, vanPelt W, Nagelkerke N, Hendrix MGR, Buiting AGM, Petit PL, et al. Increasing resistance to fluoroquinolones in Escherichia coli from urinary tract infection in the Netherlands. J Antimicrob Chemother 2000;46:223-228.

[13.] Anudumani N, Mallika M. Antibiotic resistance pattern in uropathogens in a Tertiary Care Hospital. Indian Journal for the Practicing Doctor. April2007;4(1).

[14.] Pais P, Khurana R, George J. Urinary Tract Infections: A retrospective survey of causative organisms and antibiotics prescribed in a Tertiary Care Setting. Indian J Pharmacol. 2002;34:278-280.

[15.] Astal ZE. Increasing ciprofloxacin resistance among prevalent urinary tract bacterial isolates in the Gaza Strip. Singapore Med J 2005;46(9):457-460.

[16.] Vasquez Y and Hand WL. Antibiotic susceptibility patterns of community-acquired urinary tract infection isolates from female patients on the US (Texas)-Mexico Border. Jrnl Applied Research. 2004;4(2):321-326.

[17.] Mekki AH, Hassan AN, Elsayed DEM. Extended spectrum beta lactamases among multi-drug resistant Escherichia coli and Klebsiella species causing urinary tract infections in Khartoum. J Bacteriol Res. 2010;2(3):18-21.

[18.] Pullukcu H, Aydem F, Tazbakan MI, Cilli F, Tunger A, Ulusoy S. Susceptibility of extended-spectrum beta-lactamaseproducing Escherichia coli urine isolates to Fosfomycin, Ciprofloxacin, Amikacin and TrimethoprimSulfamethoxazole. Turk J Med Sci. 2008;38(2):175-180.

Pooja Jain (1), Naveen Saxena (2)

(1) Assistant Professor, Department of Microbiology, Government Medical College, Kota, Rajasthan, India.

(2) Professor, Department of Microbiology, Government Medical College, Kota, Rajasthan, India.

Financial or Other, Competing Interest: None.

Submission 25-11-2015, Peer Review 26-11-2015, Acceptance 22-12-2015, Published 24-12-2015.

Corresponding Author: Dr. Pooja Jain, Address: 622, Dadabari, Main Road, Kota-324009, Rajasthan

E-mail: poojajain3985@gmail.com

DOI:10.14260/jemds/2015/2539
Table 1: Classification of Antimicrobial Agents used in the Study

Name of Group                       Name of Antimicrobials

Fluoroquinolones             Ciprofloxacin, Norfloxacin, Ofloxacin
Tetracyclines                             Doxycycline
Nitrofurans                             Nitrofurantoin
Penicillin                  Ampicillin, Amoxicillin, Piperacillin,
                                         Carbenicillin
Cephalosporins                 Cephalexin, Cefuroxime, Cefixime,
                             Cefuroxime, Ceftriaxone, Ceftazidime,
                                           Cefepime
Monobactams                                Aztreonam
Carbapenems                                Imipenem
Aminoglycosides                     Gentamicin, Netilmicin,
                                     Tobramycin, Amikacin
Nitrobenzene Derivatives                Chloramphenicol
Oxazolidinone                              Linezolid
Others                            Clindamycin, Cotrimoxazole,
                                          Novobiocin

Table 2: Common Uropathogens

Organisms Isolated     Number (%)

E. coli                3761(59.2%)
Klebsiella SPP         773(12.1%)
Enterococcus SPP       645(l0.1%)
Pseudomonas SPP         592(9.3%)
Citrobacter SPP         231(3.6%)
Acinetobacter SPP       152(2.3%)
Enterobacter SPP        55(0.87%)
Candida SPP             48(0.75%)
Proteus SPP             47(0.74%)
Staphylococcus SPP      27(0.42%)
Providencia SPP         12(0.18%)
Salmonella SPP          07(0.11%)

Table 3

Antimicrobials    Resistance

Ampicillin          80.4%
Ciprofloxacin        73%
Amoxicillin         70.4%
Norfloxacin          .3%
Cephalexin          49.4%
Cotrimoxazole       47.9%
Cefuroxime          47.4%
Ceftazidime         46.5%
Ceftriaxone         43.2%
Gentamicin          40.2%
Cefepime            14.4%
Ofloxacin            7.7%
Imipenem             7.5%
Carbenicillin        7.5%
Netilmycin           7.2%
Amikacin             6.9%
Aztreonam            5.8%
Tobramycin           5.6%
Nitrofurantoin       5.3%
Piperacillin         4.4%
Cefixime             2.2%
Chloramphenicol      0.4%
Novobiocin           0.1%
Linezolid            0.1%
Doxycycline          0.1%
Furomycin            0.1%

Table 4: Antimicrobial drug resistance
in the commonly isolated organisms

Name of the Antimicrobial    Resistance in Percentage

Ofloxacin                             81.4%
Netilmicin                            75.6%
Imipenem                               72%
Carbenicillin                         69.3%
Amikacin                              65.6%
Aztreonam                              55%
Tobramycin                            53.4%
Piperacillin                          37.5%

Table 5: Resistance Pattern of Pseudomonas SPP (Table4.4)

Nameoftheantimicrobia     Resistanceinpercentag

Ofloxacin                         81.4%
Netilmicin                        75.6%
Imipenem                           72%
Carbenicillin                     69.3%
Amikacin                          65.6%
Aztreonam                          55%
Tobramycin                        53.4%
Piperacillin                      37.5%

Sex distribution of UTI (Table 6)

Gender    Number of Organisms Isolated (%)

Male                 2635(41.5%)

Female               3715(58.5%)

Age distribution of UTI (Table 7)

                Most Common Isolated
                 Uropathogens From
                Different Age Groups

Age Group      Klebsiella   Entero-
E. coli        SPP          coccus SPP

NB-19   735    162          84

(17%)

20-49   1145   245          240

(32.9%)

50-79   1631   288          278

(43%)

80>     250    78           43

(7.1%)

                   Most Common Isolated
                     Uropathogens From
                   Different Age Groups

Age Group      Pseudo         Others   Total
E. coli        monas SPP(%)

NB-19   735    71             28       1080

(17%)

20-49   1145   218            248      2088

(32.9%)

50-79   1631   269            265      2731

(43%)

80>     250    34             46       451

(7.1%)
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Title Annotation:Original Article; Rajasthan, India
Author:Jain, Pooja; Saxena, Naveen
Publication:Journal of Evolution of Medical and Dental Sciences
Article Type:Report
Geographic Code:9INDI
Date:Dec 24, 2015
Words:2531
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