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Antibiotic resistance pattern of bacteria
in urinary tract infection
Done by :
Hasan abu awwad ( 0120177)
Yazan Hayel Alsoud (0120322)
Mustafa Alrawy (0126649)
Moawia Shafei ( 2120990 )
Mohammad Najdat ( 0125010)
Mahmoud Al-Saify ( 2121370 )
Under the supervision of Professor Rula Darwish
We wrote about this subject for the following reasons :
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UTI is the second largest infection after respiratory infection (6)
there is notable increase in the prevalence of antimicrobial reisitance among
patogens that cause UTI due to misuse of antibiotics (3)
the distrbution of uropathogens and thier susceptibility pattern to
antibiotics vary regionally and even in the same region , over time . so
it’s necessary to reevaluate the resistant pattern of these pathogens
(6)
the data would help the authorities to formulate antibiotic prescription
policies for a better therapeutic outcome .
Introduction
UTI is defined as the presence of microorganisms in the urinary tract that cannot be accounted
for by contamination , these infections represent a wide variety of syndromes, including
urethritis, cystitis, prostatitis, and pyelonephritis . And these syndromes are associated with an
inflammatory response to microbial invasion and can range from asymptomatic bacteriuria to
pyelonephritis with bacteremia or sepsis .
Significant bacteriuria : presence of at least 10^5 bacteria / ml of urine
Asymptomatic bacteriuria : bacteruria with no symptoms .
Epidemiology :
40-50% of female population will experience a UTI in their life .
Etiology
What are the microorganisms that are involved in UTI ?
Note : the percentages below don’t necessarily reflect the real situation in Jordan , because the
distrbution of uropathogens and thier susceptibility pattern to antibiotics vary regionally and
even in the same region , over time
Gram negative bacteria are more common than Gram positive infections , in Gram negative
bacteria , E-coli causes 75-90% of all infection , followed by Klebsilla ~2-17% and Proteus ~110% , and other minor Gram negative bacteria including Enterobacter spp , Citrobacter spp ,
Psudomonas aeruginosa
In term of Gram positive bacteria , Staphylococcus Saprophyticus caused around 20% of all
infections , they are more aggressive infections , others include Enterococcus spp and Staph
aureus
Antimicrobial Therapy
Ideal antibiotic for UTI has : adequate coverage over E-coli , Concentration in urine , Low
resistance , cost and adverse effects .
Empirical Treatment of Acute Uncomplicated Cystitis
First-line therapy
Nitrofurantoin monohydrate macrocrystals, 100 mg twice daily for 5 days
TMP-SMX, 160/800 mg twice daily for 3 days
Fosfomycin trometamol, 3g sachet in a single dose
Second-line therapy
Ciprofloxacin, 250 mg twice daily for 3 days
Levofloxacin, 250 mg or 500 mg once daily for 3 days
Amoxicillin-clavulanate, 500 mg/125 mg twice daily for 7 days
Cefpodoxime, 100-mg twice daily for 3 to 7 days
Pyelonephritis
Most episodes of uncomplicated pyelonephritis can be treated in the outpatient setting with
an empirical regimen of ciprofloxacin (500 mg twice daily for 7 days) or levofloxacin (750 mg
once daily for 5 days). Urine culture and susceptibilities need to be collected before starting
antimicrobial treatment to guide treatment. If quinolone resistance is a concern, TMP-SMX
(160/800 mg twice daily for 14 days) can be used once the antibiogram shows susceptibility to
this medication. Indications to hospitalize patients with pyelonephritis include severe
presentation, hemodynamic instability, pregnancy, kidney stones, or inability to tolerate oral
medications (5)
TREATMENT Of UTI In Case Of Pregnancy
Urinary tract infections are common during pregnancy, and the most common causative
organism is Escherichia coli. Asymptomatic bacteriuria can lead to the development of
cystitis or pyelonephritis.
Pregnant women are at increased risk for UTIs. Beginning in week 6 and peaking during
weeks 22 to 24, approximately 90 percent of pregnant women develop ureteral dilatation
Pregnant women should be treated when bacteriuria is identified . The choice of antibiotic
should address the most common infecting organisms (i.e., gram-negative gastrointestinal
organisms). The antibiotic should also be safe for the mother and fetus. Historically,
ampicill in has been the drug of choice, but in recent years E. coli has become increasingly
resistant to ampicillin.
19 Ampicillin resistance is found in 20 to 30 percent of E. coli cultured
from urine in the out-patient setting.
20 Nitrofurantoin (Macrodantin) is a good choice
because of its high urinary concentration. Alternatively, cephalosporins are well tolerated
and adequately treat the important organisms. Fosfomycin (Monurol) is a new antibiotic that
is taken as a single dose. Sulfonamides can be taken during the first and second trimesters
but, during the third trimester, the use of sulfonamides carries a risk that the infant will
develop kernicterus, especially preterm infants. Other common antibiotics (e.g.,
fluoroquinolones and tetracyclines) should not be prescribed during pregnancy because of
possible toxic effects on the fetus.
Treatment of UTI in Men :
As a general rule, all urinary tract infections (UTIs) in men are considered
complicated. because the urethra is much longer and the distance between the
anus and urethral meatus is greater than in women. In addition, the perimeatal
environment is much drier in men, and prostatic secretions confer a degree of
antibacterial activity.
-Same as female guideline but Nitrofurantoin is contraindicated
The EAU guidelines state that nitrofurantoin should not be used in men as it does
not reach reliably sufficient tissue concentrations.
Conclusions Urinary tract infection in men is much rarer than in women and
tends to be associated with underlying urological pathology. Urine culture
samples should be handled appropriately, to ensure accurate identification of the
causative organism. Prompt treatment with empirical antibiotics is indicated for
at least seven days and if, following a first mild episode of infection
,
Treatment in Children:
Acute urinary tract infections are relatively common in children, with 8 percent of girls and 2
percent of boys having at least one episode by seven years of age. The most common
pathogen is Escherichia coli, accounting for approximately 85 percent of urinary tract
infections in children.
The recommended initial antibiotic for most children with UTI is
trimethoprim/sulfamethoxazole (Bactrim, Septra). Alternative antibiotics include
amoxicillin/clavulanate (Augmentin) or cephalosporins, such as cefixime
(Suprax), cefpodoxime, cefprozil (Cefzil), or cephalexin
In Pediatrics :
Urinary tract infection (UTI) is one of the most common pediatric infections. It
distresses the child, concerns the parents, and may cause permanent kidney
damage.
Antibiotic resistance pattern of bacteria in urinary tract infection
The distribution of uropathogens and their susceptibility pattern to antibiotics vary
regionally and even in the same region , they change over time , therefore the
knowledge on the frequency of the causative microorganisms and their susceptibility to
various antibiotics are necessary for a better therapeutic outcome . also for help the
authorities to formulate antibiotic prescription policies .
For this reason , Retrospective Study was conducted in 2014 in Zarqa city / Jordan , in
order to reevaluate the resistant pattern of the pahtogens involved in UTIs , the
antibacterial susceptibility data of this study have been obtained from the records of
clinical microbiology laboratory of Prince Hashim Hospital/Zarqa .
3756 urine samples were collected from patients with UTIs symptoms , from which 392
(10.4%) show positive urine cultures , The incidence of UTI among females 318 (81%) is
higher than that for males 74(19%) , this is due to anatomic and physical factors related
to females . Bacterial isolation and identification was conducted using standard
methods ( Gram staining , colonial morphology on media , growth on selective media ,
lactose and mannitol fermentation , H2S production , catalase , oxidase , coagulase ,
indole and citrate utilization , and urease test .
The urine samples were culuterd on 5% blood agar , MacConkey and Eosin-Methylene
blue ( EMB ) agar using calibrated loops for semi-quantitative method . after incubation ,
samples with colony count equal or more than 10^5 CFU/ml were considered positive .
Table (1) : Pathogen isolates from patients with UTI .
Baceria
Escherichia coli
Klebsiella spp
Proteus spp
Psudomonas spp
Staphylococcus
aureus
Male
patients
54
14
1
2
2
Female
patients
263
32
15
8
1
% Male
% Female
Total
13.77
3.57
.25
.51
.51
67.09
8.16
3.83
2.04
.25
80.86
11.73
4.08
2.55
.76
As shown above , E.coli was the most common organism followed by Klebsiella proteus ,
pseudomonas and staphylococcus spp respectively .
, many studies showed the same results ( the leading cause is E-coli and klebsiella ) , in
2002 in Jordan , E-coli accounted for 67% of UTI which was below the reported
literature (1) .
Almost UTIs were caused by gram-negative bacteria exclusively , and they collectively
account for more than 99% of the cases
Antimicrobial Susceptibility testing
This was performed according to Clinical and Laboratory Standards Institute ( CLSI )
guidelines . 14 antibiotics were tested . the distribution of Antibiotic resistance amongst
the bacterial isolates is shown in the table (2) below (%). The 1st eight antibiotics were
tested for Gram negative , and the last six were tested for Gram positive bacteria . the
results are shown in table (2) .
Antibiotics
Cefatoxime
Cephalothin
Gentamamicin
Ampicillin
E.coli
41.46
55.06
26.58
84.18
Klebsiella
spp
50
58.70
17.39
89.13
Proteus
Spp
31.25
50
18.75
62.5
Psedomonas Staphylococcus
spp
aureus
30.0
50.0
40.0
40.0
Nitrofurantion 10.44
52.21
68.75
40.0
Norfloxacin
34.81
15.21
31.25
10.0
Cotrimoxazole 70.89
54.34
50
40.0
Naldixic acid
66.77
45.65
37.5
40.0
Pencillin
66.67
Erythromycin
100
Gentamicin
Vancomycin
0
Lincomycin
33.33
Teicoplanin
0
Cloxaciiln
33.33
Table (2) : Distribution of Antibiotics resistance amongst the bacterial isolates (%)
This study showed that E.oli ( the most common causative of UTI ) , showed a high level
of resistance to ampicillin (84.18%) , cotrimoxazole ( 70.89%) , Naldixic acid (66.77%)
and Cephalothin ( 55.06 % ) , while Klebsiella spp ( the 2nd most common causative of
UTI ) showed also the highest level of resistance to Ampicillin ( 89.13%) , then for
Cephalothin ( 58.70%) , cotrimoxazole ( 54.34%) and Nitrofurantion ( 52.21% )
respectively . Psudomonas spp that accounts for <3% of UTI has reported the highest
sensitivity for Norfloxacin . we don’t concern about gram-positive bacteria because they
account for a minoer percentage of UTI (<1% ) here in this study . the most effective
antibiotic against E.coli was Nitrofurantion , while for the other gram negative isolates
was Norfloxacin (Quinolone AB ) .
A similar study was conducted in Jordan in 2008 and published in 2001 , showed
Overall, high E-coli resistance rate was observed for ampicillin (84%), followed by
amoxicillin-clavulanic acid (74.3%), cotrimoxazole (71%), nalidixic acid (47.3%),
cephalothin (41%). Lower resistance rates were observed for amikacin (0%) followed by
Cefotaxime (11%), Ceftriaxone (11.7%), ciprofloxacin (14.5%), Norfloxacin (16.5%),
gentamicin (17.3%) cephalexin (20.9%), Ceftazidime (22.5%), cefixime (29.6%), and
cefaclor (32.8%) (2)
assessment of antibiotic resistance to fluoroquinolones over the study period
and extrapolation of the data led to the conclusion that these antibiotics could no longer
be effective
against E. coli-based urinary infections in approximately 20 years if their indiscriminate
use in
empirical treatment continues
Management and recommendations
1- We don’t prefer the use of pencillins , cotrimoxazole , Naldixic acid , Cephalothin and
cotrimoxazole in the management of UTI since E-coli exhibited high levels of resistance
to these agents . Guidelines of the American Infectious Diseases Society and the
European Society for Microbiology and Infectious Diseases suggest that
antimicrobials with a resistance rate above 20% should not be prescribed
empirically to patients with uncomplicated cystitis, unless susceptibility is
determined by prior isolation in culture (4) .
2- This reinforce the recommendation of various clinical guidelines related to
the empirical prescription of nitrofurantoin for uncomplicated cystitis
3- We noticed that the level of resistance of E-coli for Norfloxacin ( from Qunilones
antibiotics that are widely used here in Jordan to manage UTI ) has increased by two
folds from 2008 until 2014 . High resistance rates of uropathogens to quinolones
and sulfamethoxazole-trimethoprim draws attention to the choice of these drugs
on empirical treatments , Therefore, quinolones as empirical therapy must be
considered carefully .
“ these antibiotics ( Qunilones ) could no longer be effective
against E.coli-based urinary infections in approximately 20 years if their indiscriminate
use in empirical treatment continues (3) “ .
4- Regular monitoring is required to establish reliable information about susceptibility
pattern of urinary pathogens for optimal empirical therapy of patients with UTI.
References
1- ( Murshidi & Farah , 2002 ) , Alshara , 2011 .
2- Antimicrobial resistant pattern of Escherichia coli strains isolated from pediatric in
Jordan , Alshara 2011
3- Antibiotic Resistance of Bacteria Involved in Urinary Infections in Brazil: A CrosSectional and Retrospective Study , wellington Rodrigues .
4- Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, et al.
International clinical practice guidelines for the treatment of acute
uncomplicated cystitis and pyelonephritis in women: a 2010 update by the
Infectious Diseases Society of America and the European Society for
Microbiology and Infectious Diseases.
Cleveland Clinic Center for Continuing Education
56- Reterospective analysis of antibiotics resistance pattern to urinary pathogens in
a tertiary care hospital in south India