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Dr. S. MANZOOR KADRI

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These Are Research Articles By The Members Of IMIA, Medical Students, Research Workers etc.

IMIA takes no responsibility about the authencity of contents, research or standard of the published material, which is the sole responsibility of the author/s.

TO WHOM  IT MAY CONCERN

I certify that the article submitted for publication is the original work of the contributors and has not been submitted for publication or presentation any where else                                                                                  S. Manzoor Kadri

URINARY TRACT INFECTION : CURRENT SENSITIVITY AND RESISTANCE PROFILE IN Kashmir  , INDIA

   S. MANZOOR KADRI *

BASHIR GASH **

ASIF RUKHSANA *

*Jr. resident Dept. Of Microbiology Government Medical College , Srinagar , Kashmir , India

**  Epidemiologist , Kashmir Province , India

·         HOD , Dept. Of Microbiology Government Medical College , Srinagar , Kashmir , India

 

 

ABSTRACT:-

 

Urinary tract infections are common and are generally treated empirically by General Practitoners,for which they need to be aware of the locally prevalent strains and their sensitivity pattern.Since over the last few decades the resistance pattern of urinary isolates has been showing dramatic changes all over the world,it was felt clinically useful to study the existing microbiological pattern of the urinary tract infections in Kashmir valley and to assess the current sensitivity profile of the isolated organisims to the generally used antibiotics for empirical therapy in Primary  health care settings.The retrospective analysis of 324 such samples which were found positive for pathological bacteria by the Microbiology laboratory of Government Medical College Srinagar,Kashmir India revealed that 90.1% of the isolates were E.Coli followed by Klebsiella (7.7%) and Staphylococcus (1.3%).Significantly 43.6% of the E.Coli exhibited resistance to the commonly used antibiotics,and the most effective in vitro agents were found to be Amikacin followed by Gentamicin among the injectables and ciprofloxacin among the orally administered antibiotics.Other useful oral antibiotics were Nitrofurantoin,Chloramphenicol and Nalidixic acid.The organisms showed resistance to currently preferred urinary antibiotics and chemotherapeutic agents as Cotrimoxazole,Norfloxacin,Pefloxacin and Cephalexin.Conclusion was that among the orally administered antibiotics Ciprofloxacin remains the choice while other Quilolones have turned ineffective and among the injectables Aminoglycosides are still effective.

  

Key Words:-Urinary tract infection,Culture and Sensitivity of organisms,emerging resistance,most suitable agents for empirical therapy.

 

 Urinary tract infection is a common  ailment and is exceeded in frequency among ambulatory patients only by respiratory and gasterointestinal infections.Bacteria infections of the urinary tract are the commonest cause of both community acquired and nasocomial infections in patients admitted to the American hospitals (1).Urinary tract  infection accounts for about 6% of new consultations in general practice in Europe and Scandinavia (2).Women are especially prone;about 5-6% of all sexually active women have bacteriuria (3)Which in them is associated with increased mortality as assessed in life table analysis (4).The cumulative prevalence of asymptomatic bacteriuria in females increases about 1% per decade throughout life (5) why more women acquire bacteriuria with increasing age is not known.In addition to causing considerable discomfort and ill health UTI,overt as well as asymptomatic,can lead to complications within and outside the urinary tract.

  

In the developing countries,particularly in rural settings,the problem is compunded by the fact that patients are late to seek treatment.At the same time ,because of lack of facilities,vast majority of urinary infections are treated empirically and only a small minority can get pre therapy testing.Since over the past decades the sensitivity profile of the community acquired as well as nosocomical UTI has undergone drastic changes it has become necessary to periodically monitor the changing pattern of sensitivity and emerging resistance locally to provide feedback to general practitioners on the most antibiotic agents for a particular community.

 

 With this objective a retrospective study of aerobic cultures of 1,281 urine samples sent from the outpatients as well as inpatient departments of the SMHS hospital to the Microbiology laboratory of the Govt.Medical College ,Srinagar, India  during 1997-98 (With subsequent sensitivity testing of the positive isolates)was undertaken.Pathological microbes were isolated from 324 samples (25.30%) which in the vast majority of cases (90.12%) were E.Coli

 followed,in order by Klebsiella (7.7%)and staphylococcus (1.3%). Out of the total 201 female testing positive on culture 94% exhibitied E.Coli and 4.5% Klebsilla,whereas among the culture positive males 83.75% revealed E.Coli with as many as 13% showing Klebsiella. One case of pseudomonos and  two cases of mixed infections (klebsiella and E.Coli) were detected in males only.About 80% (259) samples came from the outpatient departments while only 21.1% (65) where sent from the medical and surgical wards of the S.M.H.S hospital.Majority of E.Coli and Klebsiella (80.5% and 76% respectively)Isolates had thus come from the outpatients clinics (Table#1)

 

Of the E.Coli isolates 43.57% showed resistance to the commonly used antibiotics.The highest sensitivity was shown to Amikacin followed among the injectables by the Gentamicin and among the orally administered antibiotics chloramphenicol,Ciprofloxacin,Nalidixic acid and Nitrofurantoin .In comparision  to Ciprofloxacin,Pefloxacin had a dismal invitro performance and the isolates of E.Coli showed resistance to sporidex,Tertracycline,Streptomycin and Cotrimaxazole.No strain was sensitve to Cephalexin and Norfloxacin.Such isolates from the wards and from the females followed the same general pattern while as those from the O.P.D. and male patients,most likely to be complicated,revealed much have sensitivity to antibiotics.(Table#2 and 3)

 

Of  the Klebsiella isaolates only 37.97% proved sensitive to generally used antibiotics while as 62.1% were either boder line sensitive or resistant.High degree of sensitivity was shown to Amikacin followed by Gentamycin,Ciprofloxacin,Pefloxacin,and Nalidixic acid.Wide spread resistance was evident to all other generally used Antibiotics for Emprically therapy here.(Table#2&4).The University of Calfornia study (19)revealed that nearly half of the strains of E.Coli were resistant to Ampicillin.Progressively lesser resistance was seen to Cephalexin,Cotrimoxazole and Amoxacillin/Clavulanic acid.A 7 year monitoring from 1991 till 1997 showed no resistance to Nitrofurantion and Ciprofloxacin.

 

In the 70s and 80s when almost all antibiotics,including Pencillins, Penicillin combinations,Cefalosporins,Old and new Quinolones,Aminoglycosides,trimethoprim as well as Cotrimoxazole were effective in uncomplicated UTI (23) and the general consensus was that all these could be used for emprical or calculated therapy (if a rate of resistance of 10% was acceptable) currently the opinion is that widespread emergence of resistance makes it difficult to suggest empiric treatment of urinary tract infections.(16).This is advisable in places where microbiological pretherapy analysis is possible at the primary health centre health centre level as in the U.S.A,Europe and Scandinavia.In places like ours where such facalities are available,only  inadequately  and insufficiently,at the teaching hospitals  only,the large majority of the Physicians will have to restore to empricial therapy.Singh et al (1992) in north Indian studies found that most of the isolates (63.2%) were resistant to one or more drugs,of which 41% were multidrug resistant.Most were resistant to ampicillin,tetracyclines and trimethoprims.(24).The researchers conclude that there is a high frequency of multidrug resistant strains of E.Coli in northern India,.and our study has revealed that our valley shares this resistance pattern.Other than the parenterally administered Amikacin and Gentamycin,oral Ciprofloxacin,presently considered the drug of choice for UTI caused by Gram positive as well as Gram Negative organisms in Germany,Harare,Japan and Sweden (7,15,20,23) emerges as the most effective agent.

 

Other useful orally given could be Nitrofurantoin,Nalidixic acid and Chloramphenicol.

 

It is not out place to mention that organisms isolated have shown widespread resiatance to our current favourites Amoxycillin/Ampicillin,Cotrimoxazole and Norfloxacin which evidently can not be recommended for empirical therapy in the valley.Tambic et al(1996) and Dyer et al (1998) have rightly emphasized the need for continous surviellance of the prevallence and antibiotic sensitivity pattern of microorganisims locally which should be the basis for effective therapy (18,19).Practitioners need to be kept aware of the emerging resistance patterns of infectious diseases in a community.

 DISCUSSION:-

 

UTI in adults is mostly confined to the lower urinary tract and is ascending in nature.E.Coli has been the predominant organism isolated and no significiant change has occured in this picture over the last so many decades.The researchers who assessed the microbiological pattern of the urinary isolates in the 70s and 80s found that E.Coli remained the most prominent isolate in acute UTI with an isolation frequency of more than 70% every year.(6);in Chronic UTI also E.Coli remained the most frequent species with isolation rates of 17-37%.(6).During the same  two decades some change was seen in the frequency patterns of other organism including Staphylococcus,Proteus,Klebsiella and Enterobacterium.(7).World wide studies have revealed a preponderance of E.Coli in Urinary isolates in the 70s,80s and 90s:65.3% in Japan (8),69% in Italy (9) 74% Sweden (10),75% in England (11) and upto 90% in U.S.A (12).Recent studies in Europe again have indicated that E.Coli still remains the most common isolated organism from the uncomplicated U.T.I ranging from 41.6% in Italy (13),60%Caudad (14) ,90% in England (15) to as high as 94% in Isreal (16) E.Coli was the most frequently isolated organism in community infections in England and Ireland (17) and Zagrab (18).A recent American study (19) showed that the proposition of E.Coli in the current decade has risen significantly;It accounted for 69% of positive cultures in 1991 which increased to 75% in 1994 and 81% in 1997.In Harare 88.5% of out patient urinary tact infections showed Gram negative organisms out of which 40.5% were E.coli (20).Our study revealed an isolation frequency of 90.12% for E.Coli which is not different from that seen in England,Isreal and U.S.A. Because of absence of clinical details we could not ascertain the proportion of outpatients belonging to complicated UTI nor could we find the number of uncompained UTI sent from the wards .

 

Sexwise break up revealed that E.Coli was commoner isolate (94.03%) among females as compared to 83.75% from males.Obi et al (1996) in Harare also reports that E.Coli is more common in females than males(20).On the Contrary  Klebsiella has been 3 times commoner in urine of males (13.0%:4.48%) in our analysis.Klebsiella has been the second most frequent organism isolated in our study as has been the case elsewhere (7,8,20).Many studies in Southeast Asia have shown Klebsiella to be the most frequent isolate in hospital urinary infections (7,21,22) but in our series E.Coli remained the most frequently isolated organism from the hospital acquired infections also.The results show that in our place the urinary infection is primarily caused by E.Coli whether in the community (general practice) or within the hospitals.

 

Although the spectrum of pathological bacteria isolated from the urine of patients across the globe remained largely unchanged over the past few decades there have been dramatic changes in the resistance pattern and sensitivity profile in most countries. Fakatsu et al (1992) in Japan who followed sensitivity patterns of the uncomplicated UTI from January 1988 till December 1991 found that E.Coli were sensitive to all drugs except Ampicillin,and that Klebsiella were highly sensitive to Norfloxacin.(15).A similar pattern had been seen  by Doi et al earlier who followed emerging resistance patterns from 1977 to 1984;a decrease in sensitivity of E.Coli to ampicillin in UTI had been reported by them (6).Grunneberg (1984) monitoring resistance patterns form 1973-1984 found that sensitivity continued to fall to Ampicillin/Amoxycillin,Nalidixic acid and Cephaloridine (7).Farry et al (1988) in Sweden observed increasing drug resistence in the isolated strains of E.Coli strains even to drugs not used for therapy of UTI generally (10).Schito et al (1992) in Italy observed that Amoxycillin and Norfloxacin were the least active compounds aganist E.Coli (13).Villar et al (1996) reported a wide spread resistance of E.coli to most common agents used in general practice,and among them quinolones and Nitrofurantoin were more prominent (14).Obi et al (1996) in Harare found that E.Coli as well as Klebsiella were resistant to Ampicillin,Nitrofurantoin,Cotrimoxazole and Tetracycline (20).Finkelstein et al(1998)  found high rates of resistance to Ampicillin,Cefazoline,Cefuroxime,CotrImoxazole as well as the Amoxycillin clavulanate combination (16) while the organisms were still sensitive to quinolones and Nitrofurantoin

REFERENCES:-

 

1.Reller,L.Barth.The patient with urinary tract infections.In Manual of Nephrology,Diagnosis and treatment (Ed Schrieder),1986;Little Brown and Co,Boston;Pg 99

 

2.Gaymans R,Valkenburg HA,Haverkorn MJ,Goslings WHO.A prsopective study of urinary tract infection in a Dutch general practice,Lancet 1976;2:674-7.

 

3.Maskell R.Urinary tract infection in clinical and laboratory practice.Edward Arnold,1988;1:69

 

4.Evans DA,Kass EH,Hennekens CH.Bacteriuria and subsequent mortality in women.Lancet1982;1:156-8

 

5.Kunin CM .Detection,prevention and management of UTI.1979;3rd ed;Lea and Febiger,Philadelphia.

 

6.Doi T,Takeda A,Okana M,Fujihiro S,Hantano K,Kato N,Kanemastu M,Ban Y.Hinykokika Kiyo 1987;33:12

 

7.Grunneberg RN.Antibiotic sentivities of urinary pathogens 1971-82.J Antimicrob chemother 1984;14:17-23.

 

8.Kosakai N,Igari J,Kumamoto Y,Sakai S,Shigeta S,Shiraiwa Y,Abe K,Tazaki H,Iri H,Uchida H.J Antibiot 1985;38:8;2185-229

 

9.Nava L,Fiorentini,Siena MM.Comparative study of the microbiological components in urinary Tract infection.J.Ital chemother 1989;36:69-87

 

10.Ferry S,Butman LG,Holm SE.Clinical and Bacteriological Effects of therapy of urinary Tract infection in Primary Health care:Relation to in vitro testing.Scand J Infect Disease 1988;20:5:535-44

 

11.Macleod J.Urinary Tract infection .In Davidson's Principles and Practice of Medicine.1984;395-8;ELBS-Churchill livingstone,UK

 

12.Reller LB.The patient with urinary Tract infection.Manual of Nephrology,Diagnosis and therapyEd.Schrieder,1986;Little Brown and Co,Boston;Pg 103.

 

13.Schito GC,Chezzi C,Nicoletti G,Moreddu M,Arcangelleti MC.Susceptibility of frequent urinary pathogens to Fosfomycin,trometamol and eight other antibiotics.Results of an italian multicentre study. Infection 1992;20 suppl;4s:291-5

 

14.Villar Gill J,Baeza Berruti JE,De diego sierra D,Ruiz poveda ,Garcia Rojo A.Bacteriological and Resistence in Ambulatory Urinary infections.Aten primaria 1996:18(6) 315-7

 

15.Fakatsu H,Honda N,Mizumoto H,TakiT,Mitsui K,NonomouraH.Bacteria Isolated From Urinary Tract infections and their susceptibility to New quinolones.Hinyokika Kiyo 1992;38(11):1215-23.

 

16 Finkelstein R,Kassis E,Reinhetz G,Gorenstein S,Verman P.Community acquired urinary Tract infection in Adults.J Hosp infect 1998;:38:3:193-202

 17.Scully PG,O'Shea B,Flanagan KP,Falkner FR.Urinary Tract Infection in General infection in General practice,Direct sensitivity Testing as a Potential Diagnostic Method.Ir JMed sci 1990;159:4:98100

 18.Tambic A,Tambic T,Kucisec tepes N.Prevalence and Antibiotic sensitivity pattern variations of bacterial isolates in different settings and different periods of time.Acta Med croatica1996:50:1:5-10

 19.Dyer IE,Sankay TM,Dawson JA.Antibiotic Resistance in Bacterial Urinary Tract infection;1991 to 1997.West J Med(Nov).1998;169:265-8

 20.Obi Cl,Tarupiwa A,Simango C.Scope of Urinary Pathogens isolated in the public Health bacteriology Laboratory,Harare:Antibiotic Sensitivity patterns of isolates and incidence of Haemolytic Bacteria.Cent Afri J Med 1996;42:8244-9

 

21.Chan RK,Lye WC,Lee EJ,Kumarasinghe G.Nosocomial Urinary Tract infection:A microbiological Study.Ann Acad Med,Singapore 1993;22:6:873-7

 

22.Kawamura J,Hayashi N,Okabe S,Kawahara S,Chigusa I,Araki T.Microorganisms isolated from urinary tract infections and their beta lactamase production and evaluation of clinical efficacy of Sulperazone.Hinyokika Kivo 1988;34:8:1503-14.

 

23.Naber KG,Bauerfeind A,Dietlein G,Wittenberger R.Urinary Pathogens and Bacterial Sensitivity in Hospitalised urological patients based upon clinical aspects.Scand J urol Nephrol Suppl 1987;104:47-57

 

24.Singh M,Chaudhary MA,Yadava JN,Sanyal SC.The spectrum of Antibiotic resistence in human and Veterianry isolates of E.Coli collected from 1984-86 in northern india.J.Antimicrob Chemother 1992;29:2159-68.

 

TABLE#1.Distribution of cases according to the organism isolated,sex of the patient and venue of referral.

S.                Organism                             Total                                        Females                  Males                OPD                        IPD

No.          isolated                   No                (%)                          No                (%)                          No                 (%)                No                (%)                No                (%)

1.E.Coli                                   292                (%)                          189                94.03                103                83.75 235 80.48 57  19.52

2.Klebsiella                            25                7.72                         9                4.48                         16                13.00 19  76.00 6    24.00

3.Stsphylococcus                 4                1.24                         3                1.49                         1                0.81             3                75.00  1                25.00

4.Pseudomonas                1                0.31                         -                -                               1                0.81            1                 100.00 0  -

5.Mixed (E.coli+                2                0.61                         -                -                               2                1.63              1                   50.00 1 50.00

Klebsiella)

Total                                                        324                100                          201                100                          123                100                259                          -                65                -

 

Table # 2 Sensitivity profile of E.Coli and Klebsiella isolates to commonly used Antibiotics.(*)

Antibiotic tested                Sensitive E.Coli isolates                Sensitive Klebsiella isoloates

                                                                No                           Percentage            No                           Percentage

Amikacin                                 141                          16.33%                    12                            15.19%

Gentamacin                            83                            9.61                                                                      7.60

Chloramphenicol                58                            6.72                                         1                              1.26                        

Ciprofloxacin                          51                            5.90                                         3                              3.80

Nalidixic acid                         49                            5.68                                         4                              5.06

Nitrofurantoin                          48                            5.56                                         1                              1.26

Pefloxacin                               28                            3.25                                         3                              3.80

Sporidex                                 17                            1.97                                         0                              -

Tetracycline                            6                              0.70                                         0                              -

Streptomycin                           4                              0.46                                         0                              -

Cotrinoxazole                         2                              0.23                                         0                              -

Cephazoline                           0                              -                                               0                              -

Norfloxacin                             0                              -                                               0                              -

Total                                                        487                          56.43                       30                            37.97

(*)Total number of isolates tested was 863 E.coli and 79 Klebsiella

 

 

                                                                Table# 3 Comprative Susceptibility of E.Coli  in respective groups.(in percent)

Antibiotic                                                Overall                                    Venue of                                 Sexswise                

Tested                                     Sensitivity                                              referral                                    comprassion

                                                                %                                             OPD                IPD                          Males                      Females                 

Amikacin                                 28.37                       26.77                33.62                32.39                       26.48                      

Gentamacin                            16.70                       18.90                15.52                13.07                       11.53

Chloramphenicol                11.67                       12.86                7.76                         11.37                       11.84

Ciprofloxacin                          10.26                       10.50                9.49                         13.64                       8.41

Nalidixc acid                          9.86                                         9.71                         12.93                8.52                                         10.90

Nitrofurantion                          9.65                                         9.45                         10.35                7.95                                         10.60

Total                                                        487(100)                 373(100)                114(100)                172(100)                 315(100)

 

Table# 4 Comprative Susceptibility of Klebsiella in respective groups.(in percent)

Antibiotic                                                Overall                                    Venue of                                 Sexswise                

Tested                                     Sensitivity                                              referral                                    comprassion

                                                                %                                             OPD                IPD                          Males                      Females                 

Amikacin                                 30.00                       34.61                75.00                47.06                       30.77                Gentamacin                           20.00                       23.08                -                               17.65                       23.08

Nalidixc acid                          13.33                       15.38                -                               -                                               7.70

Ciprofloxacin                          10.00                       7.69                         25.00                5.88                                         15.38

Pefloxacin                               10.00                       7.69                         -                               11.76                       7.70

Total                                                        30(100%)                26(100%)4(100%)  17(100%)                13(100%)

Fur Further Information Please Contact :

 

Dr. S. MANZOOR KADRI

Post Box # 1143

GPO, Srinagar –190001

 Kashmir , India

Contact # 91-194-46125

Facsimile : 91-194-461245 

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