Antimicrobial Susceptibility and Phage Types

A retrospective study of the patterns of antimicrobial susceptibility and phage types of 111 Salmonella typhi strains isolated in 1996 from Vietnam was carried out. The strains were tested for susceptibility to chloramphenicol, ampicillin, tetracycline, trimethoprimsulfamethoxazole, nalidixic acid, ceftazidime, ceftriaxone and ciprofloxacin. Simultaneous resistance to chloramphenicol, ampicillin, tetracycline and trimethoprim-sulfamethoxazole were present in 84 strains (75.7%). Nalidixic acid resistance was only observed in 2 multidrugresistant strains (1.8%). Twenty-one strains (18.9%) were completely susceptible to all drugs tested. All 111 strains were susceptible to ceftazidime, ceftriaxone and cipropfloxacin. The MIC values for chloramphenicol, ampicillin and trimethoprim-sulfamethoxazole corresponded with the results by disk diffusion method. On Vi phage-typing, 5 different phage types (28, A, D1, E1 and M1) were found in 12 strains (10.8%). However, most S. typhi strains were indistinguishable by this typing technique because they were degraded Vi-positive or untypeable Vipositive strains (35.1% and 54.1%, respectively). There were no correlations between antimicrobial resistance patterns and phage types in the tested S. typhi strains in this study. A combination of effective antimicrobial therapy, improved sanitation and hygiene, and vaccines reduce significantly the morbidity and mortality from typhoid fever. Under selective antibiotic pressure the organism has developed different mechanisms of antibiotic resistance. Owing to the development of bacterial resistance to chloramphenicol during the 1970s and 1980s, treatment with this drug was widely replaced by ampici l l in and trimethoprim-sulfamethoxazole. However, by the 1980s and 1990s, S. typhi developed resistance simultaneously to all drugs used for first-line treatment, namely, chloramphenicol, ampicillin and trimethoprim-sulfamethoxazole (Bhutta et al, 1992). The widespread emergence of resistance to drugs used to treat typhoid fever led to large epidemics, particularly in Asia, and complicated the treatment of this serious infection (Parry, 2004). INTRODUCTION Typhoid fever is a worldwide health problem, especially prevalent in developing countries. Globally, there are approximately 16 million cases of typhoid fever with 600,000 deaths annually (Ivanoff, 1995). The regions with a high incidence of this disease (>100/ 100,000 persons/year) include Southcentral and Southeast Asia (Crump et al, 2004). In some developing countries of Asia and Africa, the annual incidence of infection may reach 1% with case fatality rates as high as 10%. About 70% of all fatalities from typhoid fever occur in Asia (WHO, 2005). SOUTHEAST ASIAN J TROP MED PUBLIC HEALTH 488 Vol 38 No. 3 May 2007 In Vietnam, resistance to chloramphenicol was first observed in the south in 1971, and this resistance spreaded rapidly to two-thirds of S. typhi isolated (Brown et al, 1975; Meyruey et al, 1975). Ampicillin and trimethoprim-sulfamethoxazole were clinically effective alternative drugs (Butler et al, 1977). Multidrug-resistant (MDR) typhoid fever [simultaneous resistance to chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole (CmApTmSu) and other antibiotics] was first detected in the late 1980s and emerged as a problem in 1992 causing several large outbreaks over the succeeding years (Hoa et al, 1998). The initial outbreak of MDR typhoid fever was described in Kien Giang Province (southern Vietnam) in 1993 (Nguyen et al, 1993). By 1994, over 80% of all S. typhi strains isolated in southern Vietnam were multidrug-resistant (Vinh et al, 1996) while MDR strains were reported in less than 5% and 10% of cases in central and northern Vietnam, respectively (Nguyen and Tran, 1994; Pham and Dang, 1994). Three other MDR typhoid outbreaks occurred in southern Vietnam from 1993 to 1997. Some of the MDR strains from the outbreaks were associated with nalidixic acid resistance (Nguyen et al, 1993; Tran el al, 1995; Vinh el al, 1996). Strains within S. typhi are separated into a number of phage types by their patterns of susceptibility to lysis by a series of variants of a single phage, Vi-phage II, which has been adapted to the different types of typhoid bacillus. There is a high degree of correlation between the phage-type and the epidemic source of typhoid fever. Consequently, phage typing has been one of the most effective tools for the classification of the pathogen at the intraspecific level. Determination of the phage type obtained from patients is valuable for epidemiological study of infections (Anderson and Williams, 1956). So far about 106 different phage types of S. typhi have been defined and are designated by letter or number (Hampton et al, 1998). In the present study, we aimed to identify the patterns and levels of antibiotic resistance in clinical strains of S. typhi isolated in Vietnam in 1996 and to investigate Vi-phage types and their correlation to resistance patterns in selected strains. MATERIALS AND METHODS