ORIGINAL ARTICLE

Prevalence of Antibiotic Resistance among Patients with

Escherichia Coli Urinary Tract Infection in a Private Hospital at
Lahore-Pakistan
1 2
SIDRA CHEEMA , SHAFIQ UR REHMAN CHEEMA

ABSTRACT
Of 127 urine isolates from patients at national hospital and medical center 93 were positive for
Escherichia Coli (E.Coli). Out of these 93 isolates, 73%, 77%, 82% & 71% were resistant to
fluoroquinolones, trimethoprim-sulfamethoxazole (SXT), Ampicillin-sulbactam & Ceftriaxone
respectively. Resistance to Nitofurontoin, Fosfomycin, Pipericillin-Tazobactam, Cefoperazone-
Sulbactam & Carbapenems (Imipenem-Cilastatin, Meropenem) was found to be only
14%,8.7%,4.4%,1.4% & 1.1% respectively. For uncomplicated urinary tract infection (UTI) empiric
antibiotics should include Nitofurontoin and Fosfomycin. For severe and complicated infection
parenteral antimicrobial with least resistance should be used.
Keywords: Escherichia Coli, UTI, bacterial resistance, fluoroquinolones resistant

INTRODUCTION increasing resistance to commonly prescribed

antibiotics
There are an estimated 150 million urinary tract The aim of this study was to assess the
1
infections per annum worldwide .Urinary tract prevalence of antimicrobial resistance and determine
infections are the most common bacterial infections appropriate empiric antibiotic therapy among patients
in women and account for significant morbidity and with urinary tract infection secondary to E. coli.
1,2
health care costs . Among both outpatients and
inpatients, Escherichia coli is the primary urinary tract
PATIENTS AND METHODS
pathogen, accounting for 75 to 90% of uncomplicated
2,3
urinary tract infection isolates . This cross-sectional study was carried out at the
Infectious Disease Society of America clinical pathology laboratory of National Hospital &
recommends that physicians obtain information on Medical Center, Lahore, Pakistan betweenJuly1,
local resistance rates and that ongoing surveillance 2014 to June 30, 2015 for a period of one year. A
be conducted to monitor changes in susceptibility of total of 123 urine isolates from inpatient and
uropathogens. It also recommends that alternative outpatientwere received. These patients were
therapy for uncomplicated UTIs in the setting with > suffering from UTI and confirmation was made from
10 to 20% SXT resistance may include a beta lactam, their clinical records. Only 93/123 positive E.Coli
fluoroquinolones, Nitofurontoin or Fosfomycin. cultures were included for further analysis of
Fluoroquinolones, in particular ciprofloxacin, are used susceptibility and resistance patterns.Then medical
increasingly but resistance to ciprofloxacin is also records of these patients were reviewed for the
increasing. The widespread use of fluoroquinolones following variables: age, sex, type of isolate on urine
for such a common infection raises concerns culture, sensitivity and resistance pattern to different
regarding the possibility of accelerated development antimicrobials and ESBL status. No patient with
4
of resistance . positive E.Coli in urine culture was excluded based
UTI is the most common disease effecting on first or subsequent, lower or upper and
urinary tract and it is major cause of morbidity. complicated or uncomplicated UTIs.
Fluoroquinolones and beta lactam antibiotics are
commonly prescribed for patients with signs and RESULTS
symptoms consistent with uncomplicated urinary tract
infection. We noticed that poor response to empiric Of 127 patients urine isolates 93 were positive for
antimicrobial at our institution and wanted to test the E.Coli.The mean age was 52 (range= 1-93, median
hypothesis that this probably is secondary to 63).There were 30%(28/93) men and 70% (65/93)
----------------------------------------------------------------------- women. Out of these 93 urine isolates,
1
Assistant Professor Pathology, CMH Lahore Medical College 73%,77%,82% & 71% were resistant to
2
Assistant Professor of Nephrology, CMH Lahore Medical College fluoroquinolones,trimethoprim-sulfamethoxazole,
Correspondence to Dr. Shafiq ur Rehman Cheema, Ampicillin-sulbactam&Ceftriaxone respectively.
Email:[email protected] Cell: 0311-238-1111
Resistance to Nitofurontoin,Fosfomycin, piperacillin-
tazobactam,Cefoperazone-Sulbactam&carbapenems

364 P J M H S Vol. 10, NO. 2, APR – JUN 2016

 Sidra Cheema, Shafiq Ur Rehman Cheema

(Imipenem-Cilastatin, Meropenem) was found to be more sensitive to Quinolones &fluoroquinolones as

only 14%,8.7%,4.4%,1.4% & 1.1% respectively compared to men. Sensitivity of patients age less
In terms of ESBL producing organism,46% than 30 years was not much different from overall
(43/93)were positive for ESBL and 54% (50/93) were sensitivities except for Quinolones &fluoroquinolones.
negative for ESBL. All ESBL producing bacteria were E coli appeared to be more sensitive to Quinolones
resistant to ampicillin and Ceftriaxone but among &fluoroquinolones for younger patients. The following
ESBL negative, only 11/50 (22%) & 16/50 (32%) table shows the results of sensitivities &resistance
were sensitive to amoxicillin/ampicillin and pattern of E.Coli to commonly prescribed
Ceftriaxone respectively indicatingprevalence of high antimicrobial used in clinical practice..
resistance to these beta lactam. Women found to be
Table
Antibiotic Overall Overall Sensitivity Sensitivity Sensitivity Sensitivity Sensitivity
sensitivity Resistance ESBL(+) ESBL(-) Women Men age<30
TMP-SXT 22.5 77.5 16.2 24 21.1 25 32.1
Quinolones 15 85 2.3 26 18.4 7.1 32.1
Fluoroquinolones 26.8 73.2 20.9 34 30.7 17.8 35.7
Amoxil/Ampicillin 17.2 82.8 0.0 22 10.7 17.8 17.9
Ceftriaxone 29 71 2.3 32 20 17.8 17.9
Aztreonam 34.4 65.6 32.5 38 32.2 39.2 35.7
Fosfomycin 91.3 8.7 83.7 94 78.4 85.7 89.2
Nitofurontoin 86 14 81.3 86 84.6 85.7 85.7
Pipericillin- 97.8 2.2 93 98 96.9 96.4 100
Tazobactam
Cefoperazone- 95.6 4.4 90.6 100 95.3 96.4 100
Sulbactam
Carbapenems 98.9 1.4 95.3 100 98.4 96.4 100

DISCUSSION case of resistance to Nitofurontoin making it first line

10
therapy .
The microbial spectrum of uncomplicated cystitis and In USA because of low resistance to
Pyelonephritis consists mainly of Escherichia coli (75 flouroqinolones,for outpatient treatment of
to 95 percent), with occasional other species of uncomplicated Pyelonephritis we suggest
Enterobacteriaceae, such as Proteus mirabilis and ciprofloxacin (500 mg orally twice daily for seven
Klebsiellapneumoniae, and other bacteria such as days or 1000 mg extended release once daily for
5,6
Staphylococcus saprophyticus . Other gram- seven days) or levofloxacin (750 mg orally once daily
negative and gram-positive species are rarely for five to seven days) is recommended but given
isolated in uncomplicated UTIs. Therefore, local high resistance in our study we recommend
antimicrobial susceptibility patterns of E. coli in alternatives like parenteral antimicrobial agents like
particular should be considered in empiric piperacillin-tazobactam, Cefoperazone-Sulbactam
antimicrobial selection for uncomplicated UTIs. and carbapenems should be used.
The rate of resistance to fluoroquinolones (like Considerations in selecting an agent for
ciprofloxacin), beta lactam (like ampicillin and treatment of acute cystitis include efficacy, risk of
Ceftriaxone)and TMP-SXT were concerning, as adverse effects, resistance rates, propensity to cause
fluoroquinolones are now the most commonly ecological adverse effects of antimicrobial therapy
7,8
prescribed therapy for UTI . (such as selection of drug-resistant organisms and
Extended-spectrum beta-lactamases (ESBL) are development of colonization or infection with
enzymes that confer resistance to most beta-lactam multidrug-resistant organisms), cost, and drug
antibiotics, including penicillins, cephalosporins, and 11
availability . None of the antimicrobials currently
the monobactamaztreonam. Infections with ESBL- available clearly outweighs the others in terms of
producing organisms have been associated with poor optimizing each of these factors for treatment of
outcomes.Community and hospital-acquired ESBL- acute cystitis, and the optimal antimicrobial in one
producing Enterobacteriaceae are prevalent region may be different from that in another.
9
worldwide . Appropriate antimicrobials for treatment of acute
The resistance to Fosfomycin and Nitofurontoin uncomplicated cystitis in women include
was found to be low, suggesting that these agents Nitrofurantoin monohydrate (100 mg orally twice daily
should be strongly considered as a first-line empirical for 5 days); early clinical efficacy rate with 5 to 7 day
treatment for uncomplicated lower UTIs. In another regimen 90 to 95 percent based on randomized trials
study in young college women, there was not a single

P J M H S Vol. 10, NO. 2, APR – JUN 2016 365

Prevalence of Antibiotic Resistance among Patients with Escherichia Coli UTI

(11-15) and minimal resistance and ecological the setting of pyelonephritis because they do not
11
adverse effects. Nitrofurantoin should be avoided if achieve adequate renal tissue levels .
there is suspicion for early pyelonephritis, and is For inpatient with pyelonephritis requiring
contraindicated when creatinine clearance is <60 hospitalization should be treated initially with an
Trimethoprim-sulfamethoxazole Empiric TMP-SMX intravenous antimicrobial regimen such as a
should be avoided if the prevalence of resistance is fluoroquinolones, an aminoglycoside (with or without
16,17
known to exceed 20 percent so based on the ampicillin), an extended-spectrum cephalosporin, an
24
results of our study we should avoid this. extended-spectrum penicillin, or a carbapenem .
14
Fosfomycin (3 grams single dose) ; clinical The choice between these agents should be based
14
efficacy rate 91% from one randomized trial but on local resistance data and tailored on the basis of
bacterial efficacy inferior compared with other first- susceptibility results.
line agents minimal resistance and ecological Pyelonephritis caused by extended-spectrum
adverse effects. Fosfomycin should be avoided if beta-lactamase (ESBL)-producing strains should be
33,34
there is suspicion for early pyelonephritis. In our treated with a carbapenems . Empiric antibacterial
study sensitivity to Fosfomycin was also 91.7% for e coverage for ESBL-producing organisms is warranted
coli isolates so it is a good choice for uncomplicated for patients presenting with sepsis involving the
33
cystitis. These antibiotic options and suggested urinary tract .
treatment durations for acute uncomplicated cystitis Population-based studies have documented
are the same for any adult woman with acute increasing resistance of E. coli urinary isolates to
uncomplicated cystitis, regardless of age. A fluoroquinolones and trimethoprim-sulfamethoxazole;
systematic review of studies evaluating treatment of some studies have suggested that resistance has
35
cystitis in community-dwelling adults ≥65 years of increased in particular among elderly patients .
age concluded that the optimal regimens are the Strains that produce extended-spectrum beta-
same as those recommended for younger adults and lactamases (ESBL) are also increasing in frequency
that shorter antibiotic courses (3 to 6 days) resulted Nitofurontoin and Fosfomycin are active in vitro
18
in similar outcomes as longer ones (7 to 14 days) . against ESBL producing strains (36-38) In a case-
Acceptable beta lactam agents include control study including 113 patients with ESBL-
amoxicillin-clavulanate, cefpodoxime, cefdinir and producing E. coli UTIs, no resistance to fosfomycin
18,19,20
cefaclor, for duration of seven days . was detected and clinical cure rates were high (93
39
Cefpodoxime (three-day regimen) did not meet percent) . In the US, resistance to all oral options is
criteria for noninferiority to ciprofloxacin (three-day still uncommon among outpatients with E. coli
regimen) for clinical cure of acute uncomplicated cystitis. In such cases, a carbapenem is the best
21
cystitis in a randomized trial . Other beta lactams, option (e.g.,Ertapenem once daily either IV or
such as cephalexin, are less well studied but may be .IM.)When parenteral antibiotics are indicated, any
acceptable in certain settings. Ampicillin or amoxicillin choice with low resistance and high susceptibility like
should not be used for empiric treatment given poor piperacillin-tazobactam, Cefoperazone-Sulbactam
efficacy and high prevalence of resistance to these and carbapenems should be used.
22-27
agents . In our study we also found very high The study likely overestimates the prevalence of
resistance to these beta lactam antibiotics and we antibiotic resistance in E.Coli, as patients who
don’t recommend the empiric use of these antibiotics. responded empirical therapy, and presumably had
Pyelonephritis, on the other hand, is a more susceptible organism, would not have had urine
serious infection than cystitis; therefore, expected culture and sensitivity tests performed and would not
efficacy of an antimicrobial agent is of greater have been included in the study.
importance than concern about ecological adverse
11
effects . CONCLUSION
For outpatients with mild to moderate
Pyelonephritis in whom the likelihood of Fluoroquinolones and beta lactam resistance was
fluoroquinolones resistance is expected to be less found to be very high.There was little resistance to
than 10, it has been suggested to use a Nitofurontoin and fosfomycin, carbapenems,
fluoroquinolones for empiric therapy
28-32
but since in pipercillin-tazobactam, and Cefoperazone-
our study population the prevalence of resistance is Sulbactam.Extenteded spectrum beta lactamase
much higher we don’t recommend fluoroquinolones (ESBL) production confer higher resistance
for empiric use for outpatient treatment of especially to beta lactam antimicrobials without a
Pyelonephritis. In this setting of fluoroquinolones beta lactam inhibitor. For treatment of acute
resistance, other acceptable choices based on uncomplicated cystitis, we suggest to use
susceptibility data should be considered. Use of Nitofurontoin or Fosfomycin. Pyelonephritis requiring
Nitofurontoin and fosfomycin, should be avoided in hospitalization should be treated initially with an

366 P J M H S Vol. 10, NO. 2, APR – JUN 2016

 Sidra Cheema, Shafiq Ur Rehman Cheema

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21. Auquer F, Cordón F et al. Single-dose ciprofloxacin versus 3
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368 P J M H S Vol. 10, NO. 2, APR – JUN 2016