今日の臨床サポート

腸チフス・パラチフス

著者: 氏家 無限 国立国際医療研究センター 国際感染症センター

監修: 具芳明 東京医科歯科大学大学院医歯学総合研究科 統合臨床感染症学分野

著者校正/監修レビュー済:2018/04/18
患者向け説明資料

概要・推奨   

疾患のポイント:
  1. 腸チフス、パラチフスとはSalmonella entericaのいくつかの血清型で生じる全身性発熱性疾患であり、英語では“Enteric fever”と総称される。腸チフスとパラチフスの両者に臨床的な差異はない。
  1. 臨床症状は非特異的であり、初期(第1週)には菌血症による発熱、悪寒、前頭部の鈍痛、倦怠感、食欲低下、嘔気や比較的徐脈()などを認め、徐々に増悪する。発症後2週目には腹痛のほか、体幹や腹部にバラ疹()と呼ばれる2~4mm大で淡紅色の斑状皮疹を認めることがあり2~5日で自然消退する。
  1. 腸チフス、パラチフスは感染症法の3類感染症であり、診断後には直ちに保健所に届け出る必要がある。また、便中に排泄される病原体で経口感染をするため、感染症法により飲食物に直接接触する作業者に対して就業制限がある。
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  1. 渡航地域(特に南アジア、東南アジア)や検出された病原体の感受性を考慮して、培養検体採取後にセフトリアキソン(ロセフィン)やアジスロマイシン(ジスロマック)での治療を開始する。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
氏家 無限 : 特に申告事項無し[2021年]
監修:具芳明 : 特に申告事項無し[2021年]

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 腸チフス、パラチフスはSalmonella entericaのいくつかの血清型で生じる全身性発熱性疾患であり、英語では“Enteric fever”と総称される。
  1. 腸チフスとパラチフスの両者に臨床的な差異はない。
  1. 一般に無症候性のキャリアまたは活動性のある患者の便中に排泄される病原体で汚染された飲食物の摂取により経口感染する。
  1. 時に性交渉による糞口感染、標準予防策が破綻した際の院内感染が起こり得る。
  1. 感染から発症までの潜伏期は最大で3~60日[1]であるが、その多くは8~14日であり[2]、渡航歴から潜伏期の整合性を検討する。
  1. 臨床症状は非特異的であり、初期(第1週)には菌血症による発熱、悪寒[3]、前頭部の鈍痛、倦怠感、食欲低下、嘔気や比較的徐脈( エビデンス )などを認め、徐々に増悪する。
  1. 発症後2週目には腹痛のほか、体幹や腹部にバラ疹(<図表> エビデンス )と呼ばれる2~4mm大で淡紅色の斑状皮疹を認めることがあり2~5日で自然消退する。
  1. 抗菌薬開始後には、バラ疹の出現頻度が30%から1.5%に低下する[4]
  1. 消化器症状は下痢となることは少なく、嘔吐は激しくない。また便秘となることもある。
  1. 肝脾腫を伴うことがある。
  1. 比較的徐脈(<図表>)、バラ疹(<図表>)、脾腫が3徴とされるが、これらの出現率は30~50%程度である[5]
  1. 無治療の場合には徐々に高熱となり40℃までの発熱が2週間程度持続する。その後徐々に解熱し、4週間程度で改善する。
  1. 無治療の場合、10%程度の症例で3カ月程度便中に排菌が持続し、1~4%程度の症例がキャリアとなり1年以上にわたって便中に排菌が持続する[6]
  1. 2010年には、低~中等度所得国で、約1190万人が腸チフスに罹患し、約12万9千人が死亡したと推計される。うち、南アジアでの症例は700万人と全体の半数以上を占める。
  1. 現在の調査体制で全数把握疾患となった1999年以降に国内で報告された腸チフス、パラチフスの症例数はそれぞれ年間約16~90症例であり、その大部分を国外からの輸入症例が占める。<図表>
  1. 途上国に渡航する旅行者が腸チフスに罹患するリスクは10万人中220例程度と推計され、特に南アジアでのリスクが高い[8]
  1. 下水道設備がなく衛生環境が不良な地域(インド亜大陸・東南アジアなど)(<図表>)への渡航で罹患リスクが高い。
  1. わが国における2005~08年における報告(<図表>)の78~86%の報告はアジアでの国外感染であり、そのうちインドでの感染が35~37%と最も多い。
  1. わが国に承認はないが、国際的には注射の不活化多糖体ワクチン、経口の生ワクチンが利用可能であり、海外渡航における感染のリスクに応じてワクチン接種を考慮する(国内にも未承認ワクチンを提供する医療機関はある)。
  1. 感染症法の3類感染症であり、診断後には直ちに保健所に届け出る必要がある。また、食品に直接接触する作業者に対して就業制限がある。学校保健安全法で第三種感染症に指定されており、「病状により学校医その他の医師において感染のおそれがないと認めるまで」を出席停止の期間の基準としている。
問診・診察のポイント  
  1. 渡航地域、渡航期間、渡航目的、飲食物への曝露、ワクチン接種歴など、詳細な海外渡航歴を聴取することが重要となる。

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文献 

著者: Bradley A Connor, Eli Schwartz
雑誌名: Lancet Infect Dis. 2005 Oct;5(10):623-8. doi: 10.1016/S1473-3099(05)70239-5.
Abstract/Text Enteric fever--a more inclusive term for typhoid fever and paratyphoid fever--is a systemic infection caused by Salmonella enterica, including S enterica serotype Typhi (S typhi) and serotype Paratyphi (S paratyphi). In developed countries there have been two major changes in the pattern of the disease: a marked decline in its incidence and its characterisation as a predominantly travel-associated disease. The risk to travellers appears to vary by geographic region visited, with travel to the Indian subcontinent accounting for the greatest travel risk. Although the most common cause of enteric fever is S typhi, the incidence of disease caused by S paratyphi among travellers may be more important, since the available vaccines only protect against S typhi. Descriptions of the clinical presentation in travellers are scarce but severe complications and death are rare, probably due to rapid access to readily available medical care. Drug resistance reflects the situation in endemic countries, and shows a steady increase in multidrug-resistance patterns. Currently, the recommendation for first-line therapy is ceftriaxone and, where isolates have been found to be quinolone sensitive, fluoroquinolones can still be given. Preventive measures are educating travellers about hygiene precautions and vaccination. With an increase in multidrug-resistant strains, a more effective vaccine for S typhi and S paratyphi is urgently needed.

PMID 16183516  Lancet Infect Dis. 2005 Oct;5(10):623-8. doi: 10.1016/S・・・
著者: M K Bhan, Rajiv Bahl, Shinjini Bhatnagar
雑誌名: Lancet. 2005 Aug 27-Sep 2;366(9487):749-62. doi: 10.1016/S0140-6736(05)67181-4.
Abstract/Text Typhoid fever is estimated to have caused 21.6 million illnesses and 216,500 deaths globally in 2000, affecting all ages. There is also one case of paratyphoid fever for every four of typhoid. The global emergence of multidrug-resistant strains and of strains with reduced susceptibility to fluoroquinolones is of great concern. We discuss the occurrence of poor clinical response to fluoroquinolones despite disc sensitivity. Developments are being made in our understanding of the molecular pathogenesis, and genomic and proteomic studies reveal the possibility of new targets for diagnosis and treatment. Further, we review guidelines for use of diagnostic tests and for selection of antimicrobials in varying clinical situations. The importance of safe water, sanitation, and immunisation in the presence of increasing antibiotic resistance is paramount. Routine immunisation of school-age children with Vi or Ty21a vaccine is recommended for countries endemic for typhoid. Vi vaccine should be used for 2-5 year-old children in highly endemic settings.

PMID 16125594  Lancet. 2005 Aug 27-Sep 2;366(9487):749-62. doi: 10.101・・・
著者: L Ostergaard, B Huniche, P L Andersen
雑誌名: J Infect. 1996 Nov;33(3):185-91.
Abstract/Text Relative bradycardia in infectious diseases is a poorly defined term. No exact and useful definition exists and the underlying mechanisms are unknown. Despite this, the term is often used in the literature and in clinical practice both as a clinical sign for an individual patient and as a characteristic feature of certain specific diseases. In this study a definition of relative bradycardia as a clinical sign in an individual patient and a definition of relative bradycardia as a characteristic feature of a specific disease were established based on a reference population comprising 673 patients with various infectious diseases. Relative bradycardia as a clinical sign in an individual patient held no predictive value regarding the likely type of infection. Relative bradycardia as a characteristic feature of specific disease was found for typhoid fever (P = 0.003), Legionnaire's disease (P = 0.005), and pneumonia caused by Chlamydia sp. (P = 0.0005), but not for mycoplasma pneumonia. It was not found for other pulmonary infections, infections caused by other Salmonella sp., other extracellular Gram-negative infections, or viral infections. Thus, relative bradycardia as a clinical sign has no predictive value for obtaining a tentative diagnosis, but relative bradycardia as a feature of specific disease is seen in typhoid fever, Legionnaire's disease, and pneumonia caused by Chlamydia sp. It seems that relative bradycardia as a feature of specific disease only occurs in diseases caused by organisms that are both Gram-negative and intracellular.

PMID 8945708  J Infect. 1996 Nov;33(3):185-91.
著者: S A Klotz, J H Jorgensen, F J Buckwold, P C Craven
雑誌名: Arch Intern Med. 1984 Mar;144(3):533-7.
Abstract/Text A major common-source, foodborne epidemic of typhoid fever occurred in San Antonio, Tex, in the fall of 1981, involving 80 verified cases. We summarize the clinical course of our 34 patients who had a nonspecific symptom complex that included at the initial examination fever (32 patients, 93%), headache (19 patients, 57%), diarrhea (11 patients, 33%), and anorexia (ten patients, 30%). The most common initial diagnoses were urinary tract and upper respiratory tract infections. The subsequent isolation of Salmonella typhi from blood cultures was usually unexpected. Physical findings were different from two previous series originating in the United States. Hepatomegaly was noted in only 7% (two patients), splenomegaly was noted in 13% (four patients), and rose spots were noted in 5% (two patients) of the patients. Liver function test results, however, were abnormal in 32 (95%) of the 34 patients (mean SGOT, 155 IU/mL). Typhoid fever, as seen in this outbreak, was notable for its nonspecific and mild manifestation and uniformly favorable outcome.

PMID 6703825  Arch Intern Med. 1984 Mar;144(3):533-7.
著者: Christopher M Parry, Tran Tinh Hien, Gordon Dougan, Nicholas J White, Jeremy J Farrar
雑誌名: N Engl J Med. 2002 Nov 28;347(22):1770-82. doi: 10.1056/NEJMra020201.
Abstract/Text
PMID 12456854  N Engl J Med. 2002 Nov 28;347(22):1770-82. doi: 10.1056・・・
著者: Vittal Mogasale, Brian Maskery, R Leon Ochiai, Jung Seok Lee, Vijayalaxmi V Mogasale, Enusa Ramani, Young Eun Kim, Jin Kyung Park, Thomas F Wierzba
雑誌名: Lancet Glob Health. 2014 Oct;2(10):e570-80. doi: 10.1016/S2214-109X(14)70301-8.
Abstract/Text BACKGROUND: No access to safe water is an important risk factor for typhoid fever, yet risk-level heterogeneity is unaccounted for in previous global burden estimates. Since WHO has recommended risk-based use of typhoid polysaccharide vaccine, we revisited the burden of typhoid fever in low-income and middle-income countries (LMICs) after adjusting for water-related risk.
METHODS: We estimated the typhoid disease burden from studies done in LMICs based on blood-culture-confirmed incidence rates applied to the 2010 population, after correcting for operational issues related to surveillance, limitations of diagnostic tests, and water-related risk. We derived incidence estimates, correction factors, and mortality estimates from systematic literature reviews. We did scenario analyses for risk factors, diagnostic sensitivity, and case fatality rates, accounting for the uncertainty in these estimates and we compared them with previous disease burden estimates.
FINDINGS: The estimated number of typhoid fever cases in LMICs in 2010 after adjusting for water-related risk was 11·9 million (95% CI 9·9-14·7) cases with 129 000 (75 000-208 000) deaths. By comparison, the estimated risk-unadjusted burden was 20·6 million (17·5-24·2) cases and 223 000 (131 000-344 000) deaths. Scenario analyses indicated that the risk-factor adjustment and updated diagnostic test correction factor derived from systematic literature reviews were the drivers of differences between the current estimate and past estimates.
INTERPRETATION: The risk-adjusted typhoid fever burden estimate was more conservative than previous estimates. However, by distinguishing the risk differences, it will allow assessment of the effect at the population level and will facilitate cost-effectiveness calculations for risk-based vaccination strategies for future typhoid conjugate vaccine.

Copyright © 2014 Mogasale et al. Open Access article distributed under the terms of CC BY-NC-SA. Published by .. All rights reserved.
PMID 25304633  Lancet Glob Health. 2014 Oct;2(10):e570-80. doi: 10.101・・・
著者: Robert Steffen, Ron H Behrens, David R Hill, Christina Greenaway, Karin Leder
雑誌名: J Travel Med. 2015 Jan-Feb;22(1):1-12. doi: 10.1111/jtm.12171. Epub 2014 Nov 6.
Abstract/Text BACKGROUND: Existing travel health guidelines are based on a variety of data with underpinning evidence ranging from high-quality randomized controlled trials to best estimates from expert opinion. For strategic guidance and to set overall priorities, data about average risk are useful. The World Health Organization (WHO) plans to base future editions of "International Travel and Health" on its new "Handbook for Guideline Development."
METHODS: Based on a systematic search in PubMed, the existing evidence and quality of data on vaccine-preventable disease (VPD) risks in travelers was examined and essentials of vaccine efficacy were briefly reviewed. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework was used to evaluate the quality of the data.
RESULTS: Moderate-quality data to determine the risk of VPD exist on those that are frequently imported, whereas in most others the level of confidence with existing data is low or very low.
CONCLUSIONS: In order for the WHO to produce graded risk statements in the updated version of "International Travel and Health," major investment of time plus additional high-quality, generalizable risk data are needed.

© 2014 International Society of Travel Medicine.
PMID 25378212  J Travel Med. 2015 Jan-Feb;22(1):1-12. doi: 10.1111/jtm・・・
著者: S L Hoffman, N H Punjabi, R C Rockhill, A Sutomo, A R Rivai, S P Pulungsih
雑誌名: J Infect Dis. 1984 Feb;149(2):157-61.
Abstract/Text The sensitivity of duodenal string-capsule culture (DSCC) was compared to that of bone-marrow-aspirate culture (BMAC), single 3-ml blood culture (BC), and rectal-swab culture (RSC) for isolating Salmonella typhi and Salmonella paratyphi type A from patients with typhoid and paratyphoid fever. In 36 of 154 patients DSCC could not be used, usually because the patient was too ill to swallow the capsule. In the remaining 118 patients DSCC was positive in 57.6%, RSC in 35.6%, BC in 54.2%, and BMAC in 85.6%. The sensitivity of DSCC was improved by an additional 4.7% if subcultured daily for seven days. The DSCC has no advantage over the combination of RSC and BC and is inferior in sensitivity to the BMAC. However, when a BMAC cannot be obtained, the addition of the DSCC to BC and RSC can be expected to improve the isolation rate by greater than 17%, to at least 85%.

PMID 6421940  J Infect Dis. 1984 Feb;149(2):157-61.
著者: M H Gasem, W M Dolmans, B B Isbandrio, H Wahyono, M Keuter, R Djokomoeljanto
雑誌名: Trop Geogr Med. 1995;47(4):164-7.
Abstract/Text We studied the yield of blood and bone marrow (BM) cultures in 145 patients clinically suspected of typhoid fever (TF) in Indonesia. The objectives were to compare the positivity of blood culture using 3 ml versus 10 ml of blood and to examine in how far specific antibiotic treatment for TF interfered with the positivity of BM culture. Blood for culture was collected before antibiotic treatment was initiated in hospital and BM 1 to 10 days after the start of treatment. Cultures were performed with Oxgall subcultured on SS agar. Seventy-nine per cent of patients was treated for 14 days or more with oral chloramphenicol, 18% with chloramphenicol followed by ampicillin or cotrimoxazol and 3% with other antibiotics. Cultures were positive for Salmonella typhi or S-paratyphi A in 57 of the 145 patients (39.3%) when 3 ml of blood was cultured and in 58 (40%) when 10 ml of blood was cultured. BM culture was positive despite antibiotic treatment in 70 patients (48.2%); this positivity was significantly greater than that of blood cultures (p < 0.05). When we considered the positivity of BM culture in relation to the number of days on antibiotics in hospital, the yield of BM culture remained apparently unchanged during the first 5 days of treatment. This may be the consequence of slow elimination of S.typhi or S.paratyphi by the antibiotics used and could be responsible for relapses.

PMID 8560588  Trop Geogr Med. 1995;47(4):164-7.
著者: T E WOODWARD, J E SMADEL
雑誌名: Ann Intern Med. 1948 Jul;29(1):131-4.
Abstract/Text
PMID 18869867  Ann Intern Med. 1948 Jul;29(1):131-4.
著者: B M STUART, R L PULLEN
雑誌名: Arch Intern Med (Chic). 1946 Dec;78(6):629-61.
Abstract/Text
PMID 20278487  Arch Intern Med (Chic). 1946 Dec;78(6):629-61.
著者: R Bitar, J Tarpley
雑誌名: Rev Infect Dis. 1985 Mar-Apr;7(2):257-71.
Abstract/Text The appropriate therapy for intestinal perforation in typhoid fever has been controversial since the late 1880s. Around the turn of the century, surgery became the established mode of therapy, with a mortality of 69% based on 166 patients in the English-language medical literature, and continued to be the preferred treatment until the advent of chloramphenicol in 1948. At this time the surgical mortality was approximately 50%. Following the recovery of a few patients with perforation treated only with antimicrobial agents (six initially, then eventually 22), nonsurgical therapy became the accepted mode of treatment. This change was never justified and this review demonstrates this. Appropriate therapy is virtually always surgical, usually consisting of simple closure and irrigation. Chloramphenicol alone is inadequate antimicrobial therapy in a patient with perforation and must be supplemented by other antimicrobials directed against enteric aerobic gram-negative bacilli and enteric anaerobes.

PMID 3890098  Rev Infect Dis. 1985 Mar-Apr;7(2):257-71.
著者: J P van Basten, R Stockenbrügger
雑誌名: Trop Geogr Med. 1994;46(6):336-9.
Abstract/Text Typhoid fever is still a major health problem in the developing parts of the world, with an estimated annual incidence of 540 per 100,000. Probably one of the most lethal complications of typhoid fever is ileal perforation, which affects especially young men. We reviewed the literature published after 1960 on typhoid perforation in different developing countries, with special attention to the incidence and outcome of typhoid perforation. Information was obtained on a total number of 1,990 cases of typhoid perforation in 66,157 patients with typhoid fever, published in 52 reports all over the world. The overall frequency of intestinal perforation in typhoid fever was 3% with an overall mortality rate of 39.6%. In an endemic area of typhoid fever, the diagnosis of typhoid perforation should be made on physical examination. Surgery is perferable to medical treatment.

PMID 7892698  Trop Geogr Med. 1994;46(6):336-9.
著者: Toshiro Shirakawa, Bishnu Acharya, Shohiro Kinoshita, Shunichi Kumagai, Akinobu Gotoh, Masato Kawabata
雑誌名: Diagn Microbiol Infect Dis. 2006 Apr;54(4):299-303. doi: 10.1016/j.diagmicrobio.2005.10.016. Epub 2006 Feb 8.
Abstract/Text Typhoid fever is the most common clinical diagnosis among febrile patients presenting to hospital in Katmandu. Salmonella enterica serovar Typhi (S. enterica serovar Typhi) and Salmonella enterica serovar Paratyphi A (S. enterica serovar Paratyphi A) with decreased susceptibility to fluoroquinolones and resistance to nalidixic acid are common in recent years. In the present study, we examined the in vitro susceptibility to fluoroquinolones and the presence of gyrA gene mutations in 30 clinical strains of S. Typhi and 39 of S. Paratyphi A, all of which were isolated in Katmandu, Nepal, in 2003. In those strains, we found that 73.3% and 94.9% of S. Typhi and S. Paratyphi A strains contained gyrA gene mutation, and showed the resistance to a quinolone, nalidixic acid, and decreased susceptibility to fluoroquinolones, ciprofloxacin, and levofloxacin. Although fluoroquinolones may still be useful as antibiotics for the treatment of typhoid fever, clinicians should be aware of the possibility of treatment failures of infections with S. Typhi and S. Paratyphi A strains with decreased susceptibility to fluoroquinolones.

PMID 16466897  Diagn Microbiol Infect Dis. 2006 Apr;54(4):299-303. doi・・・
著者: Mandeep Walia, Rajni Gaind, Rajesh Mehta, Premila Paul, Pushpa Aggarwal, Mani Kalaivani
雑誌名: Ann Trop Paediatr. 2005 Sep;25(3):161-74. doi: 10.1179/146532805X58085.
Abstract/Text UNLABELLED: The last two decades have seen a change in the pattern of enteric fever with the emergence of multidrug-resistant strains (MDRS), particularly strains resistant to nalidixic acid.
AIM: The aim of the study was to undertake a retrospective analysis of blood culture-confirmed cases of enteric fever diagnosed at Safdarjang Hospital, New Delhi, India from January 2001 to December 2003.
METHODS: The epidemiological details, clinical features, treatment outcome and antimicrobial resistance patterns were studied.
RESULTS: Of 377 blood culture-positive cases, 80.6% were Salmonella typhi and 19.4% Salmonella paratyphi A; 21.7% were children aged under 5 years and 6.1% were under 2 years. A significant decline in MDRS was observed, from 21.9% in 2001 to 12.4% in 2003 (p=0.04). There was a significant increase in nalidixic acid-resistant Salmonella (NARS) from 56.9% in 2001 to 88.9% in 2003 (p=0.0001). Complete resistance to ciprofloxacin (MIC>4 microg/ml) was detected in only two isolates, both Salmonella paratyphi A. Minimal inhibitory concentrations (MICs) of ciprofloxacin for NARS were increased (0.125-0.5 microg/ml) but were within National Committee for Clinical Laboratory Standards susceptibility ranges. NARS had a significantly longer fever defervescence time (7.7 vs 4.7 days, p<0.001) and hospital stay (12.1 vs 8.2 days, p<0.001), and higher rates of complications (55.5% vs 24.0%, p=0.014) and mortality than nalidixic acid-sensitive Salmonella (NASS). The rate of isolation of MDRS was higher in NARS than NASS (18.8% vs 7.3%, p=0.013).
CONCLUSION: The high rate of occurrence of enteric fever in children <5 years and also of infections caused by Salmonella paratyphi A in India calls for critical re-assessment of vaccination strategy. Nalidixic acid resistance and rising MICs of fluoroquinolones in Salmonella spp pose a new global threat requiring debate on the optimum treatment of enteric fever.

PMID 16156980  Ann Trop Paediatr. 2005 Sep;25(3):161-74. doi: 10.1179/・・・
著者: Christopher M Parry
雑誌名: Trans R Soc Trop Med Hyg. 2004 Jul;98(7):413-22. doi: 10.1016/j.trstmh.2003.10.014.
Abstract/Text Multidrug-resistant (MDR) Salmonella Typhi (resistant to chloramphenicol, ampicillin, and trimethoprim-sulphamethoxazole) and isolates with reduced susceptibility to fluoroquinolones (indicated by resistance to nalidixic acid, NaR) have caused epidemics and become endemic in southern Viet Nam during the 1990s. Short courses of ofloxacin have proved acceptable for treating MDR/NaS isolates of S. Typhi (ofloxacin MIC90 = 0.06 mg/l) causing uncomplicated disease. Ofloxacin (10-15 mg/kg/d) given for 2, 3, or 5 d cured >90% of patients with an average fever clearance time (FCT) of 4 d. Less than 3% of patients relapsed or had a positive post-treatment stool culture. In contrast, the response of NaR isolates (ofloxacin MIC90 = 0.5 mg/l) to such regimens is poor. For example, ofloxacin (20 mg/kg/d) given for 7 d cured only 75% of patients, with an FCT of 7 d, and 19% of patients had positive post-treatment faecal cultures. Currently available alternatives for NaR infections include ceftriaxone, cefixime, and azithromycin. These antimicrobials are reasonably effective but expensive. New, effective, and affordable regimens are needed to treat these NaR infections. Short courses of the new generation fluoroquinolones or combinations of the available antimicrobials are possible options.

PMID 15138078  Trans R Soc Trop Med Hyg. 2004 Jul;98(7):413-22. doi: 1・・・
著者: C W Lai, R C Chan, A F Cheng, J Y Sung, J W Leung
雑誌名: Am J Gastroenterol. 1992 Sep;87(9):1198-9.
Abstract/Text A chronic carrier state of Salmonella spp is present in 0.15% of the population, and is believed to be related to the presence of a diseased gallbladder. We present a patient with common bile duct (CBD) stones, whose bile cultures repeatedly indicated Salmonella typhi, despite an adequate course of antibiotic treatment. The carrier state was abolished after removal of the CBD stones 4 months later. The chronic carrier state may be related to biofilm formation on the surface of the CBD stones. The removal of the biliary stones, which are the most likely reservoir for Salmonella spp, may be a crucial step in eradication of the carrier state.

PMID 1519582  Am J Gastroenterol. 1992 Sep;87(9):1198-9.
著者: E Hofmann, J Chianale, A Rollán, J Pereira, C Ferrecio, V Sotomayor
雑誌名: J Infect Dis. 1993 Apr;167(4):993-4.
Abstract/Text
PMID 8450268  J Infect Dis. 1993 Apr;167(4):993-4.
著者: S L Hoffman, N H Punjabi, S Kumala, M A Moechtar, S P Pulungsih, A R Rivai, R C Rockhill, T E Woodward, A A Loedin
雑誌名: N Engl J Med. 1984 Jan 12;310(2):82-8. doi: 10.1056/NEJM198401123100203.
Abstract/Text We compared high-dose dexamethasone (initial dose, 3 mg per kilogram of body weight) with placebo in a randomized, double-blind trial involving 38 patients with culture-positive, specifically defined severe typhoid fever. The patients in the two treatment groups ranged in age from 5 to 54 and were comparable at the outset. All patients received chloramphenicol. The case-fatality rate of 10 per cent (2 of 20 patients) in the dexamethasone group was significantly lower than the fatality rate of 55.6 per cent (10 of 18) in the placebo group (P = 0.003). There was no significant difference in the incidence of complications among the survivors in either group. Delirium, obtundation, and stupor were grave prognostic signs that were useful for predicting which patients were at high risk of dying before they became comatose or went into shock. Dexamethasone is unnecessary for most patients with typhoid but is recommended for all patients with suspected typhoid fever who are delirious, obtunded, stuporous, comatose, or in shock.

PMID 6361558  N Engl J Med. 1984 Jan 12;310(2):82-8. doi: 10.1056/NEJ・・・
著者: D Münnich, S Békési
雑誌名: Chemotherapy. 1979;25(6):362-6.
Abstract/Text 11 registered thyphoid carriers were treated by cholecystectomy combined with amoxycillin + probenecid in our department. On the basis of our observations (mean observation period was more than 1 year), all our patients can be considered recovered (cure rate = 100%).

PMID 520079  Chemotherapy. 1979;25(6):362-6.
著者: I Zavala Trujillo, C Quiroz, M A Gutierrez, J Arias, M Renteria
雑誌名: Eur J Clin Microbiol Infect Dis. 1991 Apr;10(4):334-41.
Abstract/Text Typhoid fever remains an important public health problem throughout the world with a higher morbidity and mortality rate in the developing countries. Early establishment of the diagnosis and prompt initiation of treatment with chloramphenicol, ampicillin or trimethoprim-sulfamethoxazole is not necessarily followed by complete resolution of the infection. Between 1% and 6% of patients with typhoid fever become chronic biliary carriers of Salmonella typhi. These carriers are potential factors in the continued transmission of the disease. The increasing emergence worldwide of strains showing multiple resistance to the agents traditionally used in therapy has encouraged investigators to seek alternatives such as third generation cephalosporins and recently the new 4-quinolones, which have greater activity against Salmonella typhi including multi-resistant strains. The fluoroquinolones seem to be the treatment of choice in those regions where resistant strains of Salmonella typhi are prevalent.

PMID 1864294  Eur J Clin Microbiol Infect Dis. 1991 Apr;10(4):334-41.・・・

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