CITATION: Tay L, Lim YS, Sng EH. 1994. Antimicrobial resistance among enteropathogens in Singapore, 1989-1992. APUA Newsletter 12(4):1-4.


Newsletter article on community-acquired bacterial pathogens in Singapore, 1999

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Antimicrobial resistance among enteropathogens in Singapore, 1989-1992
Leng Tay, Yok Seng Lim, Ewe Hui Sng
Department of Pathology, Singapore General Hospital, Singapore

Diarrheal diseases with their associated morbidity and mortality are still prevalent in many parts of the world including Singapore. The major therapeutic considerations for patients with gastroenteritis include fluid and electrolyte replacement, dietary intake, nonspecific therapy with antidiarrheal compounds and specific therapy with antimicrobial agents. The latter is not indicated for all bacterial gastrointestinal infections though it has been found to be clinically effective in cholera and shigellosis (1). Selection of antimicrobials for therapy however has been complicated by the emergence of bacterial strains resistant to multiple antimicrobials (2).

Bacterial agents commonly causing gastrointestinal infections in Singapore are Salmonella spp, Campylobacter spp, Vibrio spp, Shigella spp and others (3). Antimicrobial susceptibility of selected enteric pathogens isolated by the Enteric Bacteriology Laboratory, Department of Pathology, Singapore General Hospital during 1989-92 was determined using the method of Bauer et al. (4). Of the nine antimicrobial agents tested, only ciprofloxacin was included at a later stage, in August 1991. Most of the pathogens were isolated from stools with some from extra-intestinal sources including blood. The specimens were received from all government and restructured hospitals, clinics and institutions and from some private clinics and throughout Singapore.

Salmonella typhi and Salmonella paratyphi
Enteric fevers (typhoid and paratyphoid) are endemic in Singapore. An average of 135 typhoid and 27 paratyphoid A cases were reported each year during 1989-92 to the Ministry of the Environment. Paratyphoid B and C cases were rare. About two-thirds of typhoid and half of the reported paratyphoid A cases were imported (5).

Of the 413 S. typhi strains isolated during 1989-92, 77% were found to be resistant to one or more antimicrobial agents: 67.6% were resistant to one antimicrobial agent and 9.2% were multidrug-resistant (Table 1). Compared to the strains isolated in 1984 (6), there was increased resistance of S. typhi strains from 0 to 8% for ampicillin and trimethoprim-sulfamethoxazole, 0 to 9% for chloramphenicol, 1 to 9% for tetracycline and 60 to 76% for streptomycin. All the strains tested were susceptible to gentamicin, ceftriaxone and ciprofloxacin (Table 2).

The first local strain of S. typhi to show resistance to chloramphenicol was detected in 1989. Although 9% of S. typhi strains isolated during 1989 were resistant to chloramphenicol, only 5 (1.2%) were indigenous strains.

The most predominant antimicrobial resistance pattern was to streptomycin (.3%). 67 of the 413 strains analyzed (8.7%) showed a multiple drug resistance pattern of CTSAX (Table 3). 81.3% of the 75 strains of S. paratyphi A isolated during 1989-92 were resistant to single antibiotics (Table 1). All were found to be susceptible to chloramphenicol, kanamycin, trimethoprim-sulfamethoxazole, tetracycline, gentamicin, ceftriaxone and ciprofloxacin. 3% were resistant to ampicillin and 81% to streptomycin (Table 2). The most predominant resistance pattern was streptomycin (78.7%) followed by A (27%) (Table 3).
The antimicrobial of choice for enteric fever in most areas of the world, including Singapore, is still chloramphenicol. Although none of the
S. paratyphi A and only 6 (1.2%) of our local S. typhi strains (one each was isolated in 1989, 1990 and 1992; two in 1991) were resistant to chloramphenicol, a cause for concern is the detection of 8.7% of S. typhi strains showing multiple resistance to chloramphenicol, tetracycline, streptomycin, ampicillin and trimethoprim-sulfamethoxazole. As both ampicillin and trimethoprim-sulfamethoxazole are usually alternative choices to chloramphenicol, third-generation cephalosporins like ceftriaxone can be considered in these circumstances (7).

Other Salmonella serotypes
Salmonellosis continues to be the most common bacterial gastroenteritis in Singapore. Predominant Salmonella serotypes isolated during 1989-92 were
S. typhimurium, S. blockley, S. weltevreden and others (3). Antimicrobial susceptibility results showed 84.3% of 3,221 strains tested were drug resistant with 61.3% showing multiple resistance to two or more drugs (Table 1).

Antimicrobial resistance in non-typhoid Salmonella has increased since 1984 from 3 to 8% for ampicillin, 2 to 9% for trimethoprim-sulfamethoxazole, 3 to 15% for kanamycin, 5 to 21% for chloramphenicol and 20 to 72% for streptomycin (6). Resistance to gentamicin remained constant at 1%. Only 6 (0.2%) of the 3221 isolates tested during 1989-1992 were resistant to ceftriaxone whilst all the 1148 strains screened were susceptible to ciprofloxacin (Table 2). Common resistance patterns over the four-year period were TS (25.8%), S (13.1%), T (8.8%), CTSK (7.8%), CTSA (6.4%), TSK (3.1%) and TSX (2.7%)(Table 3).
Although the overall frequency of resistance has increased, it is important to note that the frequency varied by serotype and by specific antimicrobial (8).

Antimicrobials are usually not indicated for acute uncomplicated Salmonella gastroenteritis since treatment does not reduce the duration or severity of symptoms, may prolong convalescence and the carrier state and may result in the emergence of resistant organisms (9). They are, however, essential for treating invasive human salmonellosis.

In Singapore, S. typhimurium has been the most common human serotype for many years since an outbreak occurred in September 1971. 37 strains sent for phage typing in 1974 were found to belong to type 193 (11). Many of the S. typhimurium strains isolated from poultry (12) and pigs (13) in Singapore were found to belong to the same phage type. Hence veterinary use of antimicrobials may have affected resistance patterns in our Salmonella isolates.

Shigella
Shigellosis is also endemic in Singapore. The number of shigellosis cases had been decreasing steadily from 215 in 1989 to 35 in 1992. The predominant serotypes were
Sh. flexneri (55.3%) and Sh. sonnei (40.8%). Sh. boydii and Sh. dysenteriae were rare, both serotypes accounted for 3.9%.

The incidence of drug resistance in Shigella as a group during 1989-92 was 84.1%, with 60.6% of the strains being multidrug resistant. Sh. flexneri had a higher incidence of drug resistance than did Sh. sonnei and about 85% of its strains showed multidrug resistance in contrast to the 24.2% of Sh. sonnei isolates (Table 1).

Compared to antimicrobial resistance of strains isolated in 1984, Shigella strains isolated during 1989-92 as a group revealed decreases in resistance from 72 to 52% for ampicillin, 58 to 49% for chloramphenicol and 78 to 58% for tetracycline. Slight increases in resistance were observed for streptomycin and trimethoprim-sulfamethoxazole. Resistances to kanamycin and gentamicin remained constant (6) (Table 2). All four Shigella serotypes were susceptible to ceftriaxone and ciprofloxacin and showed low resistances to gentamicin and kanamycin. They varied, however, in resistance to the other antimicrobials tested. Sh. sonnei showed lower resistances to the various antimicrobial agents in comparison with the other three Shigella serotypes (Table 2).

Common resistance patterns encountered in Shigella species included CTSA, S and CTSAX (Table 3). Ampicillin and trimethoprim-sulfamethoxazole are effective in the treatment of shigellosis and have been the drugs of choice for the management of bacillary dysentery for the last 15 years (14). Strains of Sh. flexneri, and Sh. dysenteriae that are resistant to both drugs have been identified in other parts of the world besides Singapore (15,16). Alternatives to ampicillin and trimethoprim-sulfamethoxazole for the treatment of shigellosis include nalidixic acid, amdinocillin pivoxil or the newer quinolones (17). The latter can only be used in adults as they are not safe for children. An additional group of drugs that are beneficial for treating shigellosis are the third-generation cephalosporins such as ceftriaxone (18). Like the quinolones, these are expensive.

Vibrio cholerae 01
El Tor cholera was first introduced into Singapore in 1944 (19). It was reintroduced into Singapore in 1963 during the seventh cholera pandemic which originated in Sulawesi, Indonesia, in 1961 (20). Sporadic cholera cases continued to occur in Singapore in subsequent years with outbreaks occurring occasionally.

A total of 116 cholera cases were reported during 1989-92 to the Ministry of the Environment (5). All were caused by V. cholerae serogroup 01 (biogroup El Tor). 85% belonged to serotype Ogawa and 15% to serotype Inaba.

Drug resistance was found in 46% of the 113 isolates studied with 10.6% of the strains showing multiple drug resistance (Table 1). Compared to the 1984 data, resistance in V. cholerae strains had increased from 1 to 11% for ampicillin, 1 to 5% for kanamycin and 1 to 37% for streptomycin. All the strains remained susceptible to tetracycline, chloramphenicol and gentamicin except for 2% being resistant to trimethoprim-sulfamethoxazole (6) (Table 2). All the strains screened were also found to be susceptible to ceftriaxone and ciprofloxacin.

Predominant antimicrobial resistance patterns during the four-year period were S, A and SKA (Table 3).
Fluid and electrolyte replacement is the mainstay of cholera therapy. Antimicrobial treatment will shorten the duration of diarrhea and reduce fluid losses. Fortunately, all our
V. cholerae strains isolated so far are susceptible to tetracycline which remains the drug of choice for cholera in adults (21). Trimethoprim-sulfamethoxazole is the alternative drug for children.
Our findings revealed varying rates and patterns of resistance among different enteropathogens to specific individual antimicrobial agents. Thus, knowledge of the antimicrobial resistance patterns of our local isolates would be of value to enable rational choice of empiric antimicrobial therapy should the need to treat arise. In addition, appropriate antimicrobial therapy requires the accurate and rapid identification of the offending enteropathogen.

It is essential that monitoring of the antimicrobial resistances of enteropathogens be continued to detect emergence of resistance to drugs to which the organisms are currently still susceptible.

References

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  2. MacDonald KL, Cohen ML, Hargrett-Bean NT, et al. JAMA 1987; 1498-9.
  3. Department of Pathology, Singapore General Hospital, Singapore. Annual Reports 1989-1992.
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  5. Quarantine and Epidemiology Department, Ministry of the Environment, Communicable Disease Surveillance in Singapore 1989-92.
  6. Tay L, Lam S. Gastrointestinal infections in Southeast Asia (V). Proceedings of the 14 SEAMIC Workshop. Southeast Asian Medical Information Centre, Japan, 1988; 97-107.
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  13. Liow TM. Singapore J pri INd 1975; 3(2);136-141.
  14. Chang MJ, Kunkle LM, Van Reken D, Anderson D, Wong ML, Felgin RD. Pediatrics 1977; 59:726-9.
  15. Bennish M, Eusol A, Kay B, Wierzba T. [Letter]. Lancet 1985;2-441.
  16. Centers for Disease Control. MMWR 1986;35:753-5.
  17. Carlson JR, Thornton SA, DuPont HL, West AH. Antimicrob Agents Chemother 1983;24:509-13.
  18. Kabir I, Butler T, Thanam A. Antimicrob Agents Chemother 1986;29:645-8.
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  20. World Health Organization. Public Hlth Papers, 1970, No. 40.
  21. World Health Organization/Control Diarrhoeal Diseases/Services/1992;91.15.
 

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