Antibiotic Sensitivity Patterns in Urinary Tract Infections at a Tertiary Hospital.


Me
zue Kenechukwu*, Ofong Chinekwu*,
Nmezi Davidson*, Ugochukwu-Obi Golibe*

Dept of Medicine and Surgery, University of Nigeria Enugu Campus

 


ABSTRACT
Urinary tract infections (UTIs) are some of the most common infections experienced by humans, exceeded in frequency among ambulatory patients only by respiratory and gastrointestinal infections.It is also the most common cause of nosocomial infections in adults. A total of 1,814 urine samples were collected in sterile universal containers from patients attending University of Nigeria Teaching Hospital between April 2004 and March 2005 and studied. The commonest isolates were Escherichia coli, Staphylococcus aureus, Streptococcus faecalis and Proteus spp. (These represented 46.3%, 30.7%, 9.1% and 5.4% of isolates respectively). The Gram-positive organisms were very sensitive to Augmentin and the Fluoroquinolones. E. coli showed the highest sensitivity to Nitrofurantoin (76%) while it was also very susceptible to the Fluoroquinolones (74%).
The study clearly shows that Nitrofurantoin is a very effective first line drug for UTIs.

Key words : UTI, Urinary Tract Infection, Antibiotic Sensitivity Patterns, Antibiogram.

Introduction
Urinary tract infection (UTI) is a broad term that encompasses both asymptomatic microbial colonization of the urine and symptomatic infection with microbial invasion and inflammation of urinary tract structures(1). Apart from the outer one-third of the female urethra, the urinary tract is normally sterile(2).From a microbiologic perspective, urinary tract infection exists when pathogenic microorganisms are detected in the urine, urethra, bladder, kidney, or prostate. In most instances, growth of more than 105 organisms per milliliter from a properly collected midstream "clean-catch" urine sample indicates infection. However, significant bacteriuria is lacking in some cases of true UTI. Especially in symptomatic patients, a smaller number of bacteria (102 to 104/mL) may signify infection. In urine specimens obtained by suprapubic aspiration or "in-and-out" catheterization and in samples from a patient with an indwelling catheter, colony counts of 102 to 104/mL generally indicate infection. Conversely, colony counts of >105/mL of midstream urine are occasionally due to specimen contamination, which is especially likely when multiple species are found(3).
Urinary tract infections (UTIs) are some of the most common infections experienced by humans, exceeded in frequency among ambulatory patients only by respiratory and gastrointestinal infections(4). Every female has a 20% life time risk of coming down with a UTI(5). In children approximately 5% of girls and 1% of boys have a UTI by 11 years of age(6). It is also the most common cause of nosocomial infections in adults.
The major organisms causing UTIs in the Eastern Nigeria environment are the Coliforms, Staphylococcus aureus and Proteus spp(7). Antibiotics which have been
recommended to treat UTIs include Ampicillin, Trimethoprim-Sulfamethoxazole, Flouroquinolones and Nitrofurantoin(8). However due to incessant abuse and misuse of these antibiotics, extensive resistance of micro-organisms to these antibiotics has developed.This study is aimed at establishing the main organisms causing of UTIs in this environment and ascertaining the extent of resistance of the causal organisms to commonly prescribed antibiotics.

Literature Review
In a study done in July 1995 at Seychelles' Victoria Hospital(9), E. coli isolates from urine samples of UTI patients showed a 78.6% resistance against Ampicillin and Amoxicillin and a 54.8% resistance against Cotrimoxazole. The same E. coli isolates showed a 75% susceptibility to Gentamicin, Nalidixic acid and Nitrofurantoin. Also, Proteus spp isolated in the study showed a 100% resistance to Nitrofurantoin but were susceptible to Ampicillin, Septrin, Gentamicin, Nalidixic acid. Klebsiella spp. were resistant to Ampicillin, Cotrimoxazole but susceptible to Gentamicin, Nitrofurantoin, Nalidixic acid. Pseudomonas spp were susceptible to only Gentamicin and Azlocillin.
In a similar study conducted by Jha and Bapat(10) in Nepal in 2005, E.coli was the most prevalent organism isolated (49%) and it showed a 100% susceptibility to Nitrofurantoin and considerable resistance to amoxicillin and ciprofloxacin. S. aureus was 88.8% susceptible to 2nd generation Cephalosporin, 77.7% susceptible to Nitrofurantoin and 75% susceptible to NorfloxacinA study carried out in 1990(11) on all women aged 15- 44 who had ever presented to the GP's clinic with symptoms of UTI, it was noted that after 28 days, patients with initial amoxicillin prescription were likely to come back for a second prescription (i.e relapse with amoxicillin noted Another study carried out in 2003 by Dr Joseph Ehimmadu(12) of the Faculty of Pharmaceutical Sciences, ABU Zaria showed large isolates of Pseudomonas aeruginosa (53.4%), Staph aureus (43.3%) and E. coli (40.7%) in the urine samples. Ciprofloxacin was shown to be the most effective antibiotic and Amoxicillin the least effectivein the study.Gupta et al(13) and Prais et al(14) found out in their respective studies that a Trimethoprim and sulphamethoxazole combination was not effective for the treatment of urinary tract infections as all the uropathogens from inpatients and outpatients showed high degrees of resistance to co-trimoxazole.In Canada, Allen UD et al(15) discovered that selective antimicrobial pressure and multiple admissions to hospital were among the risk factors associated with antimicrobial resistance in children. While in Singapore, Chan RK et al (16) found out from their study of nosocomial UTIs that the two main complicating factors in nosocomial UTIs were urogenital instrumentation (70.4%) and diabetes mellitus (24.2%) and the commonest organism isolated in their study was Klebsiella spp

Materials and Methods
A total of 1,814 urine samples were collected in sterile universal containers from patients attending University of Nigeria Teaching Hospital between April 2004 and March 2005 and studied. All samples showing significant bacteriuria were studied and isolates identified using standard bacteriogical methods. Antibiotic sensitivity testing was performed on sensitivity test agar (Biotec, UK) using the disc diffusion method in accordance with the National Committee for Clinical Laboratory Standards. Interpretation as 'Sensitive' or 'Resistant' was done on the basis of the diameters of zones of inhibition of bacterial growth as recommended by the disc manufacturer. Antibiotics against which sensitivity was tested in the present study included Co-trimoxazole, Ampicillin, Ofloxacin, Ciprofloxacin, Gentamicin, Nitrofurantoin, Augmentin and Tetracycline.Statistics collected were analysed by the Statistical Program for the Social Sciences SPSS version 13.

Results
A total of 791 urine specimens (43.61% of all urine specimen received by the laboratory within the period) showed significant bacteruria and the organisms isolated were tested for antibiotic sensitivity.The commonest isolates were Escherichia coli, Staphylococcus aureus, Streptococcus faecalis and Proteus spp. (These represented 46.3%, 30.7%, 9.1% and 5.4% of isolates respectively). There were only 13 isolates of Pseudomonas spp in the series studied. (Table 1).The Gram-positive organisms were very sensitive to Augmentin and the Fluoroquinolones. S. aureus was 85% and 87% sensitive to Augmentin and Ciprofloxacin respectively while it was only 60% sensitive to Gentamicin which had a low sensitivity to gram positives. Surprisingly, Nitrofurantoin was 86% sensitive to S. aureus but only 67% sensitive to S. faecalis. The gram positives were highly resistant to Nalidixic acid, Cotrimoxazole and Tetracycline. (See Table 2).
E. coli showed the highest sensitivity to Nitrofurantoin (76%) while it was also very susceptible to the Fluoroquinolones (74%), and moderately susceptible to the Aminoglycosides (52%) however it was resistant to other antibiotics studied in the series especially Amoxicillin (12%) and Cotrimoxazole (13%). On the other hand Proteus showed a marked resistance to Nitrofurantoin (29%) but it was very sensitive to the Fluoroquinolones, Augmentin and Gentamicin. Pseudomonas spp. were only sensitive to the Fluoroquinolones (62%) and were relatively resistant to other antibiotics in the series studied. (Table 2)Irrespective of the organism isolated, the Fluoroquinolones were active against 80.3% of all organisms isolated while Nitrofurantoin was active against 75.2% of all organisms. Cotrimoxazole was active against only 13.6% of organisms isolated.


Table 1: Organisms Isolated

Organism

Frequency

Percent

E. coli

366

46.3

S. aureus

243

30.7

Non Lactose Fermenting Enterobacteriaceae

2

.3

Klebsiella spp

13

1.6

Proteus spp

43

5.4

S. viridans

6

.8

S. faecalis

72

9.1

S. epidermidis

21

2.7

Pseudomonas

13

1.6

Beta Hemolytic Streptococcus

3

.4

S. pyogenes

4

.5

S. albus

5

.6

Total

791

100.0

 

Table 2: Antibiotics Sensitivity Pattern (to different organisms).

 

 

E. coli

S. aureus

S. faecalis

Proteus spp.

Pseudomonas

Amoxicillin

Sensitive
Resistant

13%
87%

55%
45%

68%
32%

31%
69%

0%
100%

Augmentin

Sensitive
Resistant

34%
66%

85%
15%

77%
23%

61%
39%

0%
100%

Ofloxacin / Ciprofloxacin

Sensitive
Resistant

74%
26%

87%
13%

86%
14%

86%
14%

62%
38%

Gentamicin

Sensitive
Resistant

52%
48%

60%
40%

34%
66%

58%
42%

31%
69%

Nalidixic acid

Sensitive
Resistant

44%
56%

21%
78%

12%
88%

38%
63%

14%
86%

Nitrofurantoin

Sensitive
Resistant

76%
24%

86%
14%

67%
33%

29%
70%

14%
86%

Cotrimoxazole

Sensitive
Resistant

12%
88%

17%
83%

12%
88%

8%
92%

14%
86%

Tetracycline

Sensitive
Resistant

17%
83%

32%
68%

39%
61%

15%
85%

14%
86%

 Table 3: Overall Antibiotic Sensitivity (irrespective of isolate).

Antibiotic

% Sensitive

% Resistant

Amoxicillin

34.3

65.7

Augmentin

57.9

42.1

Ofloxacin/Ciprofloxacin

80.3

19.7

Gentamicin

52.5

47.5

Nalidixic Acid

34.2

65.8

Nitrofurantoin

75.2

24.8

Cotrimoxazole

13.6

86.4

Tetracycline

23.3

76.7

 

 



Discussion and Conclusion

Escherichia coli is still the major causative organism in Urinary Tract Infections as affirmed in this study accounting for almost half off all cases(7). The role of Staph aureus as a cause of UTI is gradually increasing and this may be due to an increasing virulence.The Fluoroquinolones have always been a reliable therapeutic intervention in UTI because of their broad spectrum activity as well as strong action on gram-negatives. However it is advocated that they should be used as a last line (not a first line antibiotic) due to their serious side effects profile especially younger patients and their cost. Some low cost alternatives which were used in the past include Cotrimoxazole, Amoxicillin, Augmentin, and Nitrofurantoin. From this study, it can be seen that Cotrimoxazole is virtually useless against pathogens that cause UTI as it was only active against about 14% of all isolated organisms. Amoxicillin and Augmentin are only slightly better.A clear alternative as a first-line drug against UTI before culture and sensitivity is Nitrofurantoin. It showed strong activity against about 75% of all isolated organisms and was very active against Escherichia coli and Staph aureus particularly. It is also very cheap and readily available in developing countries. However it has a very weak activity against Proteus spp and Pseudomonas spp. It has also been shown to be very safe in pregnancy(17) and also a recent study in India showed that Nitrofurantoin had the best in-vitro susceptibility profile against E.coli(18). The consistent and high-level susceptibility of E. coli to nitrofurantoin may be influenced by nitrofurantoin's narrow spectrum of activity, limited indication (treatment of acute cystitis), narrow tissue distribution (low or undetectable serum concentrations), and limited contact with bacteria outside the urinary tract(19). There is a reluctance among doctors to prescribe
Nitrofurantoin and this may be due its sideEffect profile but it is clearly a very important drug in Urinary Tract Infections.This study also shows clearly that there is clearly little benefit in Gentamicin in UTIs except indicated specifically by an antibiogram as the drug is expensive and has a large side effect profile and its activity against all organisms causing UTIs is about 50:50. In conclusion one can truly affirm that the choice of drugs in the treatment of UTI is quite narrow today due to the widescale resistance that the common UTI pathogens show to drugs which have been used previously. Drugs like Cotrimoxazole which used to be the mainstay for outpatient treatment of UTI cannot be considered as effective first line therapy due to this massive resistance. But it is clear that Nitrofurantoin still has a role to play in the treatment of UTI as its antibiotic sensitivity profile is very effective.

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