Correspondence
Typhoid Fever
N Engl J Med 2003; 348:1182-1184March 20, 2003
- Article
To the Editor:
In their review article about typhoid fever, Parry et al. (Nov. 28 issue)1 describe the clinical features of infection with Salmonella enterica serotype typhi but do not mention renal failure as an important complication. We have reviewed data for all hospitalized adults with proven enterobacterial infection during a two-year period. Patients with chronic renal failure were excluded. Renal failure was defined as a serum creatinine concentration of more than 1.5 mg per deciliter for men and more than 1.3 mg per deciliter for women. Of 107 adults included in the study, 44 had salmonella infection and 63 had gastroenteritis caused by other pathogens. Acute renal failure was present in 16 patients in the salmonella group and 3 patients in the comparison group. In both groups, all patients recovered renal function without undergoing hemodialysis. The groups differed only in terms of the levels of C-reactive protein, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase. Values for variables reflecting hydration status did not differ between the two groups.
Renal insufficiency in patients with enterobacterial infections has been reported in several case reports, and dehydration and rhabdomyolysis are the most accepted causes of renal insufficiency.2,3 We postulate that a toxic injury occurs, since the association between endothelial dysfunction and chronic inflammation or infection has been documented.4 Reversible renal endothelial injury may explain the pathogenesis of renal insufficiency caused by the salmonella toxin. In our region, salmonella gastroenteritis in adults is frequently complicated by acute renal failure, and dehydration or rhabdomyolysis does not usually explain this complication.
4 ReferencesKarin Janssen van Doorn, M.D.
Denis Pierard, M.D., Ph.D.
Dierik Verbeelen, M.D., Ph.D.
Academisch Ziekenhuis Vrije Universiteit Brussel, 1090 Brussels, Belgium
hendrica.janssenvandoorn@az. vub. ac. be 1
Parry CM ,Hien TT ,Dougan G ,White NJ ,Farrar JJ . Typhoid fever. N Engl J Med 2002;347:1770-1782
Full Text | Web of Science | Medline2
Sion ML ,Hatzitolios A ,Toulis E ,Kounanis A ,Prokopidis D . Rhabdomyolysis and acute renal failure associated with Salmonella enteritidis bacteremia. Nephrol Dial Transplant 1998;13:532-532
CrossRef | Web of Science | Medline3
Campistol JM ,Perez Villa F ,Montoliu J ,Moreno A ,Revert L . Rhabdomyolysis and acute renal failure associated with Salmonella enteritidis infection. J Hosp Infect 1989;14:267-268
CrossRef | Web of Science | Medline4
Hingorani AD ,Cross J ,Kharbanda RK , et al. Acute systemic inflammation impairs endothelium-dependent dilatation in humans. Circulation 2000;102:994-999
Web of Science | Medline
To the Editor:
In the typhoid capitals of the world, such as Kathmandu, Nepal, and New Delhi, India,1 there are still many cases of severe typhoid every year. Severe typhoid is defined by delirium, obtundation, stupor, coma, or shock. Yet very few, if any, hospitals use the high-dose dexamethasone treatment (3 mg per kilogram of body weight as an initial dose, followed by eight doses of 1 mg per kilogram every six hours) that was recommended on the basis of the Indonesian study2 cited by Parry et al. A Medline search revealed no other study using such high doses of dexamethasone for severe typhoid in adults. Because severe typhoid continues to affect persons in these resource-poor countries, it may be prudent to determine whether the results of this Indonesian study are reproducible before advocating high-dose corticosteroids in the treatment of severe typhoid. Perhaps a joint venture of organizations such as the Centers for Disease Control and Prevention and hospitals in this part of the world would be useful to determine the reproducibility of this important Indonesian study.
2 ReferencesBuddha Basnyat, M.D.
Nepal International Clinic, 3596 Kathmandu, Nepal
rishibas@wlink.com. np 1
Sinha A ,Sazawal S ,Kumar R , et al. Typhoid fever in children aged less than 5 years. Lancet 1999;354:734-737
CrossRef | Web of Science | Medline2
Hoffman SL ,Punjabi NH ,Kumala S , et al. Reduction of mortality in chloramphenicol-treated severe typhoid fever by high-dose dexamethasone. N Engl J Med 1984;310:82-88
Full Text | Web of Science | Medline
To the Editor:
The review of typhoid fever by Parry et al. largely refers to adults (only 361 of the 3507 patients for whom data are shown in Table 2 are children) and includes a disproportionate number of trials from one country (Vietnam). The majority of cases of typhoid fever in areas where typhoid is endemic occur in children.1,2 The trials reported are disproportionately hospital-based, whereas typhoid in children is usually managed in outpatient settings. Therefore, the pooled analysis and rates of clinical failure reported with first-line agents such as chloramphenicol may not accurately reflect experience with this agent in children.
Multidrug resistance by S. enterica serotype typhi has led to widespread use of fluoroquinolones. However, resistance has emerged rapidly, and failures of quinolone therapy are increasingly reported.3 At our institution, 18 percent of isolates from children (65 of 366) showed reduced susceptibility to ciprofloxacin (minimal inhibitory concentration [MIC], >0.125 μg per milliliter), and 4 percent of the isolates were fully resistant (MIC, >1 μg per milliliter) in 2002. In contrast, susceptibility to chloramphenicol has reemerged (70 percent of isolates were susceptible in 2002). Similar trends have been reported in other areas.4 In Pakistan, ciprofloxacin is 25 times as expensive as chloramphenicol and is not registered for pediatric use. Therefore, in our view, chloramphenicol remains the agent of choice for the treatment of uncomplicated typhoid in children.
4 ReferencesAnita K.M. Zaidi, M.B., B.S.
Rumina Hasan, M.B., B.S.
Zulfiqar A. Bhutta, M.B., B.S., Ph.D.
Aga Khan University Medical College, 74800 Karachi, Pakistan
anita.zaidi@aku. edu 1
Sinha A ,Sazawal S ,Kumar R , et al. Typhoid fever in children aged less than 5 years. Lancet 1999;354:734-737
CrossRef | Web of Science | Medline2
Bhutta ZA . Impact of age and drug resistance on mortality in typhoid fever. Arch Dis Child 1996;75:214-217
CrossRef | Web of Science | Medline3
Mermin JH ,Villar R ,Carpenter J , et al. A massive epidemic of multi-drug resistant typhoid fever in Tajikistan associated with consumption of municipal water. J Infect Dis 1999;179:1416-1422
CrossRef | Web of Science | Medline4
Wasfy MO ,Frenck R ,Ismail TF ,Mansour H ,Malone JL ,Mahoney FJ . Trends of multiple-drug resistance among Salmonella serotype Typhi isolates during a 14-year period in Egypt. Clin Infect Dis 2002;35:1265-1268
CrossRef | Web of Science | Medline
Author/Editor Response
The list of complications in our review of typhoid was intended to highlight common complications but inevitably could not be exhaustive. As van Doorn and colleagues point out, renal failure and nephritis have been reported, but these complications are uncommon.1 Of 309 consecutive patients admitted to our hospital in Vietnam with blood-culture–positive enteric fever, 12 (3.9 percent) had an increased serum creatinine concentration (>1.5 mg per deciliter), but in only 2 patients (<1 percent) was the renal failure clinically significant (unpublished data).
Despite the results from Indonesia, where high-dose dexamethasone treatment was shown to reduce mortality among patients with severe typhoid treated with chloramphenicol,2 we agree with Basnyat that few hospitals use dexamethasone as recommended. Whether corticosteroids provide less benefit in patients with severe typhoid fever when they are treated with the more potent fluoroquinolones remains to be determined.
We agree with Zaidi et al. that typhoid fever in areas where typhoid is endemic is predominantly a childhood disease, but we disagree that our pooled analysis of treatment trials focused disproportionately on adults and trials from Vietnam. Our Table 2 included all the published randomized, controlled clinical trials we could obtain with the use of standard strategies for searching the literature. Of the 3507 patients in the trials we cited, 1243 (35 percent) were children. We believe the information in the table to be representative of the available published literature.
Zaidi et al. argue that chloramphenicol should remain the treatment of choice for typhoid in children, since resistance has decreased in some areas3 whereas quinolone resistance has increased and fluoroquinolones are expensive. They report 70 percent susceptibility to chloramphenicol in Karachi, Pakistan, in 2002. This still leaves 30 percent of patients in whom chloramphenicol will be ineffective. S. enterica serotype typhi with reduced susceptibility to ciprofloxacin was isolated from a small number of patients in the Tajikistan epidemic, but ciprofloxacin rather than chloramphenicol was used for treatment, and this was considered by the authors to have contributed to the low mortality rate.4,5 Short (3-to-7-day) courses of fluoroquinolones are more effective than the traditional 14-to-21-day courses of chloramphenicol and, depending on the source of fluoroquinolones, may be less expensive.
We believe that the fluoroquinolones are the current treatment of choice for typhoid fever in all age groups and that this is well supported by the available published evidence. Continued surveillance of resistance levels is clearly important for detection of the emergence of new patterns of resistance. We would welcome further randomized trials, particularly in children, to increase the evidence base in this important and neglected disease.
5 ReferencesChristopher M. Parry, M.B.
University of Liverpool, Liverpool L69 3BX, United KingdomTran Tinh Hien, M.D.
Hospital for Tropical Diseases, Ho Chi Minh City, VietnamNicholas J. White, M.D., D.Sc.
Wellcome Trust–Mahidol University Hospital for Tropical Diseases, Bangkok, ThailandJeremy J. Farrar, M.B., D.Phil.
Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
jeremyjf@hcm.vnn. vn 1
Huckstep RL. Typhoid fever and other salmonella infections. Edinburgh, Scotland: E & S Livingstone, 1962.
2
Hoffman SL ,Punjabi NH ,Kumala S , et al. Reduction of mortality in chloramphenicol-treated severe typhoid fever by high-dose dexamethasone. N Engl J Med 1984;310:82-88
Full Text | Web of Science | Medline3
Mermin JH ,Villar R ,Carpenter J , et al. A massive epidemic of multidrug-resistant typhoid fever in Tajikistan associated with consumption of municipal water. J Infect Dis 1999;179:1416-1422
CrossRef | Web of Science | Medline4
Murdoch DA ,Banatvala NA ,Bone A ,Shoismatulloev BI ,Ward LR ,Threlfall EJ . Epidemic ciprofloxacin-resistant Salmonella typhi in Tajikistan. Lancet 1998;351:339-339[Erratum, Lancet 1998;351:1592.]
CrossRef | Web of Science | Medline5
Wasfy MO ,Frenck R ,Ismail TF ,Mansour H ,Malone JL ,Mahoney FJ . Trends of multiple-drug resistance among Salmonella serotype Typhi isolates during a 14-year period in Egypt. Clin Infect Dis 2002;35:1265-1268
CrossRef | Web of Science | Medline
- Citing Articles (3)
Citing Articles
1
Jung Min Oh, Na Ra Lee, Hyung Eun Yim, Kee Hwan Yoo, Woon Yong Jeong, Young Sook Hong, Joo Won Lee. (2010) Acute Tubulointerstitial Nephritis with Renal Failure Complicated by Typhoid Fever. Journal of the Korean Society of Pediatric Nephrology 14:2, 236
CrossRef2
Zulfiqar A. Bhutta. (2006) Typhoid Fever. Infectious Diseases in Clinical Practice 14:5, 266-272
CrossRef3
M. D. Lewis, O. Serichantalergs, C. Pitarangsi, N. Chuanak, C. J. Mason, L. R. Regmi, P. Pandey, R. Laskar, C. D. Shrestha, S. Malla. (2005) Typhoid Fever: A Massive, Single-Point Source, Multidrug-Resistant Outbreak in Nepal. Clinical Infectious Diseases 40:4, 554-561
CrossRef
