Saleem Hafiz ( Mid East Medical Center, Karachi. )
Farangis Habib ( Clifton, National Innstitute of Child Health, Karachi. )
Naeem Ahrnad ( Punjab Medical College, Faisalabad, Allied Hospital P.M.C. Faisalabad. )
Irshad-ul Haq ( Punjab Medical College, Faisalabad, Allied Hospital P.M.C. Faisalabad. )
Rafaqat Husain ( Punjab Medical College, Faisalabad, Allied Hospital P.M.C. Faisalabad. )
Typhoid group of fevers pose a major threat and are a cause of high morbidity and mortality in the tropical countries. Over the last decade there has been a steady increase in the development of multiresistant strains of Salmonellae all over the world. Multiresistance ranges between 5% to 86%. In a recent study in Pakistan multidrug resistance in Salmonellae has increased to over 39%. Hence alternative therapy is needed. Fluroquinolones are an effective alternative requiring a shorter course of treatment than conventional antimicrobial agents. Lomefloxacin because of its longerhaif life and convenient BD dose was used in a multicentre study to treat cases of typhoid group of fevers including cases due to multiresistant isolates. In order to overcome the challenge presented by the multiresistant salmoneallae, a dual purpose multicentre study was conducted in two stages. The first stage included a vitro study and the second in vivo study. Two hundred local salmonellae isolates were collected and their sensitivity and minimum inhibitory concentrations were determined by standard methods. Two hundred and fourteen patients clinically suspected of suffering from typhoid groups of fevers were given Lomefloxacin 200 mg. BD for 14 days. Forty percent of Salmonellae isolates were found to be multiresistant while only 2% were found to be resistant to Fluroqunilones. The mean MIC 90 was found to be 0.06 mg/L Lomefloxacin was found to be effective in over 97% cases for treating typhoid group fevers including the ones due to multiresistant isolates. The side effects were found to be minimal and transient (JPMA 48: 168, 1998).
Typhoid is a very important disease in the developing countries where potable water which plays a major role in the spread of enteric diseases is still a rare commodity1. Typhoid fever is a severe, debilitating and potentially life threatening illness. Salmonella typhi, S. paratyphi A and B are important because of their frequent association with severn disease and bacteremia2-4. These serotypes are endemic in developing countries and results in high morbidity and mortality. The organisms invade the bowel mucosa and multiply in the submucosa and depending upon the virulence of the strain and the host response, they may invade the blood stream, lymphatic tissue or both5-7. The situation is more complicated by the fact that a high percentage of the isolates are resistant to the three commonly used antibiotics i.e. Cotrimoxazole, Ampicillin and Chloramphenicol8. As multiresistance is increasing, there is great room for the use of alternative therapy.
To overcome the challenge presented by the mulliresistant salmonellae, a dual purpose multicentre study was conducted in two stages. The first stage included in vitro study and the second stage was in vivo study.
Methods and Subjects
In Vitro Study
Two hundred local Salmonellae isolaates were obtained from Karachi, Lahore and Rawalpindi/Islamabad. These were consecutively collected routine isolated from the blood of patients with Typhoid group of fevers confirmed by API and Serological tests. Their sensitivity and minimum inhibitoiy concentration was determined by sensitivity discs and agar dilution method6 using Brain Heart infusion agar. The Discs were standard discs manufactured by DIFCO USA9. The in-vitro study was conducted at one centre. Isolates from the other centres were isolated, identified and transported to Karachi on agar slopes where they were reconfirmed and all tests performed for sensitivity and MIC. Fifty isolates of Salmonealla included Salmonella typhi 30, Salmonella paratyphi A 10 and Salmonella paratyphi B 10. There were taken randomly from the 200 isolates and minimum iithibitoxy concentration to Lomefloxacin was carried out at Karachi centre by incorporating the antibiotic in Brain Heart infusion agar and inoculating by multipoint inoculator (Denley).
In Vivo Study
An open multicentre trial was conducted to evaluate the safety and efficacy of Lomefloxacin (2x200 mg for 14 days). In all 214 patients clinically suspected of suffering from typhoid group of fevers were asked for their consent and detailed history was taken. Blood was collected for Haematology, Biochemistry and Microbiological tests including serological tests. Then the patients were given Lomefloxacin 200 rug BD for 14 days after which blood cultures were taken and after 21 days three consecutive stool samples were collected to evaluate the eradication of Salmonella species. The in-vivo study was conducted at Karachi, and Faisalabad.
Typhoid fever is a very common disease seen in the developing countries, the main promoting factor being contaminated water. Typhoid is endemic in Pakistan and usually a higher frequency is seen in the wanner months. There is a gradual increase in the multiresistant strains in the community6 thus causing tremendous difficulties in the treatment of typhoid fevers.
The in-vitro study suggested that 99% of the isolates are sensitive to Lomefloxacin hence a in-vivo study was conducted. It is interesting to note that of the 220 patients included in the study, only 9.5% had received no medication before presentation. This is quite common in countries where medicines ate available over the counter leading to self medication. The most vulnerable age group was found to be 20-29 years. This could be due to the fact that individuals in this age group are adventurous and consume food which is exposed to contamination. The most common clinical symptom was found to be gastrointestinal upset. The culture waspositiveonly in 100 (46.8%) cases this could be due to thefact that the Laboratory standards are not the same orbecause most of the patients had taken some medication prior to presentation. Widal test was positive in 137 patients and is probably the test which is relied onby most of the local physicians.
Lomefloxacin (2x200 mg) was found to be effective in treating Typhoid group of fevers in 97.6% of patients which inicuded patients who had multiresistant salmonella isolates. The mean MIC of Salmonella isolates was found to be 0.5 uG/ML, which is generally achievable at all body sites. The pathogen was eradicated in 98% cases hence the drug was found to be effective in eliminating the possibility of conversion of patients into the carrier state. This would help in the Epidemiological control of the disease.
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