Single vs multidrug therapy in enteric fever
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《美国医学杂志》
Kanchi Kamakoti CHILDS Trust Hospital (KKCTH), Chennai, India
The emergence of multidrug resistant S.typhi (MDRST) and concern about delayed response to quinolones have resulted in a lot of anxiety among treating physicians.
We carried out a comparative analysis of 62 cases of enteric fever proven by blood culture during 2001 to 2002, out of which 37 (59%) cases received a single drug (either a quinolone or cephalosporin) and 25 ( 40.3%) cases received 2 drugs simultaneously. The clinical course, complications, total duration of fever, time taken for defervescence of fever after starting therapy were analyzed retrospectively.
Majority (29) of the cases (46.78%) belonged to the age group above 5 years and 9 cases (14.4 %) were below 1yr. The male and female distribution of cases was 21 (34%) and 41 (66%) respectively. Gastro-intestinal symptoms were observed in 46 (75%) cases with jaundice, with bleeding manifestations occurring in 4 of them. Hepatomegaly and splenomegaly were observed in 28 (46%) and 23 (37%) cases respectively, and hepatosplenomegaly was present in 22 (36%) cases.
Regarding the drug therapy given, single drug therapy with a quinolone was given in 15 cases and 22 children received Ceftriaxone alone. Only one child received Ciprofloxacin as a single drug. In the group of 25 cases who received multidrug therapy, 19 (30.6%) cases received a combination of Ceftriaxone with Ofloxacin, with the other combinations being cefixime with ofloxacin in 2 (3.22%), Cefotaxime with Ofloxacin in 3 (4.83%) and Ceftriaxone with Ciprofloxacinin 1(1.6%).
The total durations of fever from the beginning of illness to the time of defervescence in the single drug group and multiple drug group were 13.54 days and 13.84 days respectively. Mean duration for defervescence of fever after initiation of antimicrobial therapy in the single drug group was 5.24 days and mean duration in the multi-drug group was 4.32 days. The difference in the total duration of fever and the time taken for the defervescence of fever after initiation of antimicrobial therapy in the two groups were not statistically significant (p >0.01).
Increasing MIC for Ciprofloxacin and failure of therapy in spite of in vitro sensitivity have been reported.[1] A gradual decrease in the clinical efficacy of Quinolone mono therapy in enteric fever has been observed.[2],[3] An epidemic of Ciprofloxacin resistant typhoid has been reported. In the present study, there was no significant difference in the total duration of fever or the time taken for the defervescence of fever after initiation of therapy in the single and multidrug groups. This reinforces the traditional recommendation of treatment of enteric fever with one drug at a time.
There have been very few reports of improved efficacy of multidrug therapy in enteric fever. Chloramphenicol- furazolidine combination[4] and cephalexin-gentamicin combination have been reported to be effective. Recommendation has earlier been made for the combined therapy of a quinolone with cephalosporin or aminoglycoside in quinolone resistant and complicated enteric fever.[1] Usage of more than one drug may increase the risk of side effects and may result in increasing resistance to quinolones and cephalosporins in addition to increase in the cost of therapy.
We conclude that therapy with a single drug is sufficient in enteric fever and administration of multiple drugs should be restricted to unresponsive cases.
References
1. Jesudasan MV, Malathy B, John TJ. Trend of increasing levels of minimum inhibitory concentration of ciprofloxacin to Salmonella Typhi. Indian J Med Res 1996; 103 : 247-249.
2. Prabha Adhikari M R, Baliga S. Ciprofloxacin - resistant typhoid with incomplete response to cefotaxime. J Assoc Physicians India 2002 Mar; 50 : 428-429.
3. Rodrigues C, Mehta A, Andrews R, Joshi VR. Clinical resistance to ciprofloxacin in Salmonella typhi. J Assoc Physicians India 1998 Mar; 46(3) : 323-324.
4. Bairwa A, Meena KC, Gupta M. Chloramphenicol- furazolidone combination in enteric fever. Indian Pediatr 1995 Jan; 32(1): 109.(Balasubramanian S, Rajesw)
The emergence of multidrug resistant S.typhi (MDRST) and concern about delayed response to quinolones have resulted in a lot of anxiety among treating physicians.
We carried out a comparative analysis of 62 cases of enteric fever proven by blood culture during 2001 to 2002, out of which 37 (59%) cases received a single drug (either a quinolone or cephalosporin) and 25 ( 40.3%) cases received 2 drugs simultaneously. The clinical course, complications, total duration of fever, time taken for defervescence of fever after starting therapy were analyzed retrospectively.
Majority (29) of the cases (46.78%) belonged to the age group above 5 years and 9 cases (14.4 %) were below 1yr. The male and female distribution of cases was 21 (34%) and 41 (66%) respectively. Gastro-intestinal symptoms were observed in 46 (75%) cases with jaundice, with bleeding manifestations occurring in 4 of them. Hepatomegaly and splenomegaly were observed in 28 (46%) and 23 (37%) cases respectively, and hepatosplenomegaly was present in 22 (36%) cases.
Regarding the drug therapy given, single drug therapy with a quinolone was given in 15 cases and 22 children received Ceftriaxone alone. Only one child received Ciprofloxacin as a single drug. In the group of 25 cases who received multidrug therapy, 19 (30.6%) cases received a combination of Ceftriaxone with Ofloxacin, with the other combinations being cefixime with ofloxacin in 2 (3.22%), Cefotaxime with Ofloxacin in 3 (4.83%) and Ceftriaxone with Ciprofloxacinin 1(1.6%).
The total durations of fever from the beginning of illness to the time of defervescence in the single drug group and multiple drug group were 13.54 days and 13.84 days respectively. Mean duration for defervescence of fever after initiation of antimicrobial therapy in the single drug group was 5.24 days and mean duration in the multi-drug group was 4.32 days. The difference in the total duration of fever and the time taken for the defervescence of fever after initiation of antimicrobial therapy in the two groups were not statistically significant (p >0.01).
Increasing MIC for Ciprofloxacin and failure of therapy in spite of in vitro sensitivity have been reported.[1] A gradual decrease in the clinical efficacy of Quinolone mono therapy in enteric fever has been observed.[2],[3] An epidemic of Ciprofloxacin resistant typhoid has been reported. In the present study, there was no significant difference in the total duration of fever or the time taken for the defervescence of fever after initiation of therapy in the single and multidrug groups. This reinforces the traditional recommendation of treatment of enteric fever with one drug at a time.
There have been very few reports of improved efficacy of multidrug therapy in enteric fever. Chloramphenicol- furazolidine combination[4] and cephalexin-gentamicin combination have been reported to be effective. Recommendation has earlier been made for the combined therapy of a quinolone with cephalosporin or aminoglycoside in quinolone resistant and complicated enteric fever.[1] Usage of more than one drug may increase the risk of side effects and may result in increasing resistance to quinolones and cephalosporins in addition to increase in the cost of therapy.
We conclude that therapy with a single drug is sufficient in enteric fever and administration of multiple drugs should be restricted to unresponsive cases.
References
1. Jesudasan MV, Malathy B, John TJ. Trend of increasing levels of minimum inhibitory concentration of ciprofloxacin to Salmonella Typhi. Indian J Med Res 1996; 103 : 247-249.
2. Prabha Adhikari M R, Baliga S. Ciprofloxacin - resistant typhoid with incomplete response to cefotaxime. J Assoc Physicians India 2002 Mar; 50 : 428-429.
3. Rodrigues C, Mehta A, Andrews R, Joshi VR. Clinical resistance to ciprofloxacin in Salmonella typhi. J Assoc Physicians India 1998 Mar; 46(3) : 323-324.
4. Bairwa A, Meena KC, Gupta M. Chloramphenicol- furazolidone combination in enteric fever. Indian Pediatr 1995 Jan; 32(1): 109.(Balasubramanian S, Rajesw)