The antibiotic of choice for the treatment of typhoid fever in most parts of the world is still chloramphenicol. Ampicillin and cotrimoxazole have been used in recent years. Selection of antimicrobials for therapy has been complicated by the emergence of Salmonella typhi strains resistant to the above mentioned antibiotics. Blood and/or bone marrow cultures of 30 adult patients grew S. typhi that was resistant to chloramphenicol, ampicillin and cotrimoxazole. However, these strains were sensitive to cefotaxime, ceftrioxone, aztreonam and ofloxacin. Ofloxacin 400 mg twice a day was given orally to these patients for 14 days. All patients recovered with no untoward side effect. We concluded that ofloxacin can be used as a drug of choice for typhoid fever, in those adult patients who are infected with S. typhi resistant to chloramphenicol, ampicillin and cotrimoxazole

Ashfaq, M K

Farooqui, B J

Ishaq, M

Khan, M A

English

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eCommons@AKUSection of Cardiology Department of MedicineAugust 1990Therapeutic implications of ofloxacin in thetreatment of typhoid fever caused by multiplyresistant Salmonella typhiM IshaqAga Khan University, ishaq.mohammad@aku.eduB J. FarooquiAga Khan UniversityM K. AshfaqAga Khan UniversityM A. KhanAga Khan UniversityFollow this and additional works at: https://ecommons.aku.edu/pakistan_fhs_mc_med_cardiolRecommended CitationIshaq, M., Farooqui, B. J., Ashfaq, M. K., Khan, M. A. (1990). Therapeutic implications of ofloxacin in the treatment of typhoid fevercaused by multiply resistant Salmonella typhi. Journal of Pakistan Medical Association, 40(8), 176-178.Available at: https://ecommons.aku.edu/pakistan_fhs_mc_med_cardiol/89THERAPEUTIC IMPLICATIONS OF OFLOXACIN IN THETREATMENT OF TYPHOID FEVER CAUSED BYMULTIPLY RESISTANT SALMONELLA TYPHIPages with reference to book, From 176 To 178 Mohammad Ishaq, M. Ata Khan  ( Department of Medicine, The Aga Khan University/Hospital, Karachi. ) Bader J. Farooqui, M. Khalid Ashfaq  ( Department of Microbiology, The Aga Khan University/Hospital, Karachi. ) ABSTRACT The antibiotics of choice for the treatment of typhoid fever in most parts of the world is stillchloramphenicol. Ampicillin and cotrimoxazole have been used in recent years. Selection ofantimicrobials for therapy has been complicated by the emergence of Salmonella typhi strains resistantto the above mentioned antibiotics. Blood and/or bone marrow cultures of 30 adult patients grew S.typhi that was resistant to chloramphenicol, ampicillin and cotrimoxazole. However, these strains weresensitive to cefotaxime, ceftrioxone, aztreonam and ofloxacin. Ofloxacin 400mg twice a day was givenorally to these patients for 14 days. All patients recovered with no untoward side effect. We concludedthat ofloxacin can be used as a drug of choice for typhoid fever, in those adult patients who are infectedwith S. typhi resistant to chioramphenicol, ampicillin and cotrimoxazole (JPMA 40: 176, 1990).INTRODUCTION Typhoid fever is an acute and systemic illness. Although the incidence has decreased in the West,typhoid fever is still endemic in Karachi, as it is in other parts of the world with poor sanitation1-3. Thecommonest organism which causes typhoid fever is Salmonella typizi and less so are Salmonellaparatyphi A, Salmonella paratyphi B, and Salmonella paratyphi C4. The diagnosis of typhoid fever isusually suspected on clinical ground and confirmed on the basis of isolation of the organism fromblood5. In the absence of antimicrobial therapy, blood cultures are positive in over 80% of patients seenin the first week of illness6. Antimicrobial therapy diminishes possibility of recovery of the causativeagents from blood. In these patients cultures of supplementary site such as bone marrow is a bettersource of organism than blood7. The antimicrobial of choice for typhoid fever in most areas of theworld is still chloramphenicol8,9. Ampicillin is also effective in the treatment of typhoid fever10 .Several studies have demonstrated a slower response rate to ampicillin than chloramphenicol10,11.Trimethoprim-sulfamcthoxazole has been used in recent years in the treatment of typhoid fever12.Strains of Salmonella typhi resistant to chloramphenicol have been reported in recent years fromMexico, Vietnam and India13. Ampicillin is recommended as an alternative to chloramphenicol asantibiotic therapy for typhoid fever caused by chloramphenicol resistant strains of Salm onella typhi14.Only occasional strains of Salmonella typlii are known to be resistant to both chloramphenicol andampicillin15. Trimethoprim-sulfamethoxazole is the drug of choice for typhoid fever caused bychloramphenicol or ampicillin resistant strains of Salmonella typhi16. Over a period of three years 3224patients attended emergency room and consulting clinic of the Aga Khan University Hospital Karachi,for pyrexia of unknown origin. Blood cultures from all of these patients and bone marrow fromselective patients were collected and sent to Microbiology laboratory of The Aga Khan UniversityHospital for culture. Total positive isolated were 13% out of which 3 1.5% were Salmonella species.Further sub typing of species showed Salmonella typhi in 83%. Antibiotic sensitivities result of thesestrains showed that approximately 30% were resistant to ampicillin, chloramphenicol andcotrimoxazole. We report management of 30 such patients suffering from typhoid fever caused bySalmonella typhi resistant to the first line antibiotics (chioramphenicol, ampicillin and cotrimoxazole).The aim of this study was to determine the effectiveness of ofloxacinin the treatment of such patients.MATERIALS AND METHODS Samples of blood and/or bone marrow were collected from 30 patients suspected for typhoid fever.Each blood sample (4-5 mls) or bone marrow sample (0.5 — 1.Oml) was collected in each of the 2blood culture bottles containing 45ml of aerobic medium (brain heart infusion brOth) and anaerobicmedium (thioglycolate broth). Bottles were immediately transported to the laboratory and incubated at37°C for 7 days. Gram stain film was made from each bottle daily for 7 days. All bottles were subcultured after 24,48,72 hours and 7th day of incubation on to blood agar and MacConkey's media. Nonlactose fermenting colonies from MacConkey’s plate were biochemically speciated using API 20E*strips. Serological confirmation was done by type specific sera. Antibiotic sensitivity testing of allisolates was performed by the method described earlier17. The antibiotic discs used were anipicillin(10mcg), cotrimoxazole (25mcg), chloramphenicol (30mcg), cefotaxime (3Omcg), aztreonam (30mcg),ceftrioxone(3Omcg) and ofloxacin (5mg).RESULTS A wide variety of clinical presentations were observed in these 30 patients (Table 1).The blood and/or bone marro* cultures from all the 30 patients grew S. typhi at varied times afterincubation (Table II).Approximately 7% of the samples grew typhi on either day 1, 4 or S post incubation. However, 53.3%and 26.7% of the samples grew S. thphi on day 2 and 3 post incubation, respectiyely. The antibioticsensitivity test showed all the isolates of S. typhi were resistant to ampicillin, cotrimox4zole andchloramphenicol, however they were sensitive to cefotaxime, aztreonam, ceftrioxone and ofloxacin. Allpatients were initially treated with the first line antibiotic therapy (ampicillin, cotrinioxazole orchloramphenicol), Eleven patients were prescribed ampicillin 1gm 8 hourly,? patients’receivedcotrimoxazole D.S. 12 hourly and 12 patients were given chloramphenicol 1gm 6 hourly. Treatmentwas reviewed after the antibiotic sensitivity results were obtained. All patients were then givenofloxacin, 400mg twice a day, orally for 10 to 14 days. Temperature of all these patients) settled within48 to 72 hours after the ofloxacin therapy.DISCUSSION This study clearly shows that most common cause of typhoid fever in Karachi is S. typhi as all theblood and/or bone marrow cultures grew this organism within 5 days of incubation, with over 50%showing growth of the organism 4t5 hours of incubation. The drugs of choice in typhoid fever arechloramphenicol, ampicillin and cotrimoxazole5,13,15. All patients were initially treated with theseantibiotics, but did not respond within 48 hours and in some cases even after 5 days of treatment. Thisobservation indicated the infection with resistant S. typhi which was confirmed by microbiologicalresults. At this point ofloxacin was administered to these patients. !n the recent past ofloxacin had beentested in vitro for its efficacy against S. typhi. The minimum inhibitory concentration (M!C) rangedfrom 0.03 to 0.12 mcg16,17.. Similarly the mean MICs of cefotaxime, aztreonam, ceftrioxone for S.typhi has been shown to be less than 0.97 mcg18. The selection of ofloxacin for our patients was donebecause the drug is effective in vitro16, can be administered orally therefore eliminates the cost ofhospitalization and is relatively less expensive than the other newer antibiotics. The recommended doseof ofloxacin in gram negative systemic infections is 200mg twice a day. As these patients are seriouslyill, theywere given 400mg twice a day. Fever subsided within 72 hours after administration of thistherapy. The treatment was continued for 14 days. No untoward effects were observed. Ofloxacin is agood drug in S. typhi infection resistant to the first line antibiotics. However this drug should riot beused in children under 14 years of age and in pregnant women. Further studies with a larger group ofpatients are recommended to evaluate the dose and effectiveness of this drug to substantiate ourconclusions.REFERENCES 1. Jamal, F., Yasin, M.S.M., Abdullah, R. et al. Salmonella aggluti nation in normal and adult sera in anendemic area. J. Diarrhoeal Dis. Res., 1986; 4 : 74.2. Black, it B., Cisneros, L., Levine, M.M., Banfi, A., Lobos, H. and Rodrigucs, H. Case-control studyto identify risk factors for pediatric endemic typhoid fever in Santiago, Chile. Bull. WHO., 1985; 63:899.3. Punjabi, N.H., Haffman, S.L., Edman, D.C. et al. Treatment of severe tyhoid fever in children withhigh dose dexamethasone. Pediat. Infect. Dis. J., 1988; 7: 598-6004. Gupta, S.P., Gupta, M.S., Bhardwai, S., et at. Current clinical patterns of typhoid fever; a prospectivestudy. J. Trop. Med. Hyg., 1985; 88: 377.5. Hook, E.W. Salmonella species (including typhoid fever), in prin ciples and practice of infectiousdiseases. Edited byG.L Mandell, R.G. Douglas Jr. and J.E;Bennet. New York, Wiley, 1985, p. 1256.6. Stuart, B.M. and Pullen, RL. Typhoid; clinical analysis of 360 cases. Arch. Intern. Med., 1946; 78 :629.7. Gilman, RN., Terminal, M., Levine, M.M. et at. Relative efficacy of blood, urine, rectal swab, boneniarrowand rose spot cultures for recoveiyofSalntonella typhi in typhoid fever. Lancet, 1975; 1:1211.8. Chin, T.D.Y. Therapy of Salmonellosis. Ration. Drug Ther., 1976;10:19. Anderson, E.S. Chloramphenicol-resistant Salmonella typhi. Lan cet, 1973; 2: 1494.10. Kayc, D., Rocha, H., Eyekmans, Let al. Comparison of parenteral ampicillin and parenteralchloramphenicol in the treatment of typhoid fever. Ann. N.Y. Acad. Sci., 1967; 145 L :423.11. Robertson, R.P., Wahab, M.F.A. and Raasch, F.O. Evaluation of chloramphenicol and ampicillin insalmonella enteric fever. N. Engi. J. Med., 1968; 278: 171.12. Snyder, M.J., Perroni, J., Gonzalez, O., Palomino, C., Gonzalez, C., Music, S., Dupont, I-LL.,Hornick, RB. and Woodward, T.E. Trimethoprim — sulfamethoxazol in the treatment of typhoid andparatyphoid fevers. J. Infect. Dis., 1973; 128 (suppl) : 734.13. Paniker, C.KJ. and Vimala, K.N. Transferable chloramphenicol resistance in Salmonella typhi.Nature, 1972; 239: 109.14. Pillay, N., Adams, E.B. and North Coombes, D. Comparative trial of amoxycillin andchloramphenicol in treatment of typhoid fever in adults. Lancet, 1975; 2: 333.15. McHugh, G.L., Hopkins, O.C., Moeflering, R.C. et aL Salmonella typhimurium resistant to silvernitrate, chloramphenicol and ampiciflin. Lancet, 1975; 1 : 235.16. Butler, T., Rurnans, L., and Arnold, K. Response of typhoid fever caused by chloramphenicol-susceptible and chloramphenicol resistant strains of Salmonella typhi to treatment with trimethoprim-sulfamethoxazole. Rev. Infect. Dis., 1982; 4 : 551.17. J3auer, A.W., Kirby, W.M.M., Sheris, J.C. and Turck, M. Antibiotic susceptibility testing by astandardized single disk method. Am. i. Clin. Pathol., 1966; 45 : 493.18. Goossens, H., Vanhoof, R., DeMol, P., et al. In vitro susceptibility of Salmonellae to antimicrobialagents. Antimicrob. Chemother., 1984; 13 : 559.19. 1-lannan, A. In vitro activity of ofloxacin against 210 clinical isolates of typhoid salmonelae.Infection, 1986; 14 (Suppl. 4): 5243.

Therapeutic implications of ofloxacin in the treatment of typhoid fever caused by multiply resistant Salmonella typhi

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Therapeutic implications of ofloxacin in the treatment of typhoid fever caused by multiply resistant Salmonella typhi

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