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Treatment of typhoid carriers with amoxicillin. Correlates of successful therapy.

Fifteen chronic enteric carriers of Salmonella typhi were treated with amoxicillin trihydrate, 2 g by mouth, three times per day. Nine of ten patients who were able to take the full amoxicillin regimen were cured; among five patients treated with a lower daily amoxicillin dosage because of gastrointestinal (GI) side effects, only two were cured (P less than .05). The mean serum amoxicillin concentration at termination of therapy was higher (P less than .01) in five patients who were cured (10.4 +/- 1.6 microgram/ml) than in the four who failed (3.0 +/- 0.7 microgram/ml), although the latter values were all above the minimal inhibitory concentrations for infecting organisms. This study suggests that amoxicillin treatment of chronic typhoid carriers could be enhanced by treating with doses sufficient to provide suprainhibitory serum concentrations of the antibiotic. However, GI intolerance to amoxicillin could limit this therapeutic approach.

Administration, Oral↗

Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever).

BACKGROUND: Fluoroquinolones are recommended as first-line therapy for typhoid and paratyphoid fever, but how they compare with other cheaper antibiotics and different fluoroquinolones is unclear. OBJECTIVES: To evaluate fluoroquinolone antibiotics for treating enteric fever in children and adults compared with other antibiotics, different fluoroquinolones, and different treatment durations of the same fluoroquinolone. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (August 2004), CENTRAL (The Cochrane Library Issue 3, 2004), MEDLINE (1966 to August 2004), EMBASE (1974 to August 2004), LILACS (1982 to August 2004), conference proceedings, reference lists, and contacted researchers. SELECTION CRITERIA: Randomized controlled trials of fluoroquinolones in people with blood or bone marrow culture-confirmed enteric fever. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the methodological quality of trials and extracted data. We calculated the odds ratio (OR) for dichotomous data with 95% confidence intervals. We analysed norfloxacin separately. MAIN RESULTS: Thirty-three trials met the inclusion criteria; 22 had unclear allocation concealment, and 29 were not blinded. Three trials exclusively included children, and two studied outpatients. The main analysis examined clinical failure, microbiological failure, and relapse. Compared with chloramphenicol, fluoroquinolones were not statistically significantly different for clinical (544 participants) or microbiological failure (378 participants) in adults; they reduced clinically diagnosed relapse in adults (OR 0.14, 0.04 to 0.50; 467 participants, 6 trials), but this was not statistically significant in participants with blood culture-confirmed relapse (121 participants, 2 trials). Compared with co-trimoxazole, we detected no statistically significant difference (82 participants, 2 trials). Among adults, fluoroquinolones reduced clinical failure compared with ceftriaxone (OR 0.08, 0.01 to 0.45; 120 participants, 3 trials), but showed no difference for microbiological failure or relapse. We detected no statistically significant difference between fluoroquinolones and cefixime (80 participants, 1 trial) or azithromycin (152 participants, 2 trials). In trials of hospitalized children, fluoroquinolones were not statistically significantly different from ceftriaxone (60 participants, 1 trial, involving norfloxacin) or cefixime (82 participants, 1 trial). Norfloxacin had more clinical failures than other fluoroquinolones (417 participants, 5 trials). Trials comparing different durations of fluoroquinolone treatment showed no statistically significant differences (693 participants, 8 trials). AUTHORS' CONCLUSIONS: Many trials were small, and methodological quality varied widely. Although enteric fever most commonly affects children, trials in this group were particularly sparse. Insufficient data in all comparisons preclude any firm conclusions to be made regarding superiority of fluoroquinolones over first-line antibiotics in children and adults.

Adult↗

Systemic lupus erythematosus-associated catastrophic antiphospholipid syndrome occurring after typhoid fever: a possible role of Salmonella lipopolysaccharide in the occurrence of diffuse vasculopathy-coagulopathy.

We report a case of well-documented typhoid fever in a 30-year-old woman with inactive systemic lupus erythematosus with asymptomatic lupus anticoagulant and high-titer anticardiolipin antibody (aCL). Despite prompt eradication of the Salmonella typhi obtained with appropriate antibiotic therapy, multiple organ system dysfunction occurred. The central nervous system was involved, with ischemic infarcts in the occipital lobes. High-dose corticosteroid therapy failed to improve the neurologic manifestations, which responded to repeated plasmapheresis. A sharp fall in aCL and anti-beta2-glycoprotein I antibody titers was recorded before the start of plasmapheresis. At the same time, IgM and IgG antibodies to Salmonella group O:9 lipopolysaccharide became detectable; the IgM antibodies disappeared within 4 months, whereas the IgG antibodies remained detectable during the next 13 months. Despite treatment with high-dose corticosteroids and cyclophosphamide, rapidly progressive glomerulonephritis developed, leading to chronic renal failure. There is convincing evidence of a link between the S. typhi infection and the ensuing catastrophic syndrome in this patient, probably precipitated by bacterial antigens.

Adult↗

Typhoid ileal perforations: why such mortalities?

The average mortality of 25 per cent in typhoid perforations of the ileum treated operatively could be reduced, because only half of the cases die of the lethal complications of myocarditis and toxaemia. The results of the present study show important differences between the preoperative fluid and electrolyte therapy of survivors and non-survivors as well as differences in the urinary output per hour. The perforation-operation interval as well as duration of the illness also have prognostic significance. The problem of enteric fever must ultimately be solved by preventive measures, but the results of this review indicate that attention to these factors could halve the present mortality.

Adolescent↗

The emergency surgical management of massive and persistent intestinal haemorrhage due to typhoid fever: a report of 3 cases.

The classic approach to the management of intestinal haemorrhage due to typhoid infection has been conservative, with sedation, rest to the intestine, blood transfusion and antibiotics. However, in the event of massive and persistent haemorrhage which does not respond to conservative measures, emergency resection should be considered. Surgical resection by removing the major ulcer-bearing areas will stop the bleeding and the intestine is not friable.

Adult↗

Typhoid perforation.

Typhoid perforation of the bowel carries a high risk of mortality and is a common surgical problem in many developing countries. This review examines the pathogenesis, and discusses diagnosis and management.

Adult↗

Alterations of host resistance to mouse typhoid infection by sex hormones.

The effect on mouse typhoid infection of a 3-day treatment of female virgin mice with 1 mg/day of female sex hormones (estrogen or progesterone), maintaining the same hormonal levels observed in pregnant mice for 30 days, was investigated in order to clarify the mechanisms of altered resistance during pregnancy. Estrogen-exposed mice were more susceptible to the intraperitoneal challenge with Salmonella typhimurium as compared with the vehicle control mice, while progesterone treatment increased the survival times of mice. Estrogen exposure increased the number of peritoneal cells after treatment, but the inflammatory cellular response after infection was significantly suppressed. Although the estrogen-treated and vehicle control mice had the same degrees of peritoneal cellular responses after infection, the death rates in the estrogen-treated mice were higher than those in the vehicle control mice against challenge with 1 LD50 of S. typhimurium. On the other hand, progesterone treatment resulted in the marked influx of peritoneal cells after treatment was terminated, and also it induced a significant increase in the number of peritoneal cells after infection. Although survival times in the progesterone group were higher than those in other groups, all progesterone-treated mice died after a challenge with 1,000 LD50 of S. typhimurium. These results suggest that progesterone enhances nonspecific resistance by increasing the influx of peritoneal cells after infection, while estrogen affects the acute inflammatory responses.

Animals↗

Two outbreaks of typhoid fever related to the war in Bosnia and Herzegovina.

Two outbreaks of typhoid fever caused by Salmonella typhi of the same phagotype (A, biotype II), and antibiotic susceptibility are reported. Both occurred during the war in Bosnia and Herzegovina. The first outbreak appeared among the refugees from the town of Jajce. The second outbreak appeared among the inhabitants in the village of Vidosi near Livno. This report describes main clinical, epidemiological and laboratory findings for 22 patients treated in Split University Hospital, Croatia, in the period November 1992-January 1993. Possible epidemiological connections between those two outbreaks are discussed.

Adolescent↗

Clinical experience in detecting endotoxemia with the limulus test in typhoid fever and other Salmonella infections.

Semiquantitative estimates of circulating endotoxin were performed by the limulus test in patients suffering from typhoid fever and other salmonelloses. The test was positive in a large number of cases. However, no clearcut correlation was found between existence of endotoxemia, as such, and pyrexia. A correlation with recent bacteremia was found for highest levels of endotoxin activity. In minor salmonelloses a striking prevalence of positive cases was observed in the age group under one year. These findings were discussed in relation to the diagnostic and pathogenetic facets of the problem.

Adolescent↗

Surgical complications of typhoid fever: enteric perforation.

Typhoid fever remains a prevalent disease in developing nations as the result of adverse socioeconomic factors. The most frequent complication, and principal cause of mortality, is perforation of the terminal ileum. This report presents our experience with 96 patients surgically treated at Cayetano Heredia University Hospital in Lima, Peru from 1972 to 1986. The clinical characteristics and the diverse surgical procedures utilized in the management of these patients are reviewed.

Humans↗

Ciprofloxacin versus ceftriaxone in the treatment of multiresistant typhoid fever.

A randomized trial comparing ceftriaxone (3 g given parenterally per day for 7 days) to ciprofloxacin (500 mg given orally twice a day for 7 days) in the treatment of blood culture positive typhoid fever was conducted. Twenty patients were openly randomized to receive ciprofloxacin and 22 to receive ceftriaxone. The outcome was classified as clinical failure in 6 patients (27%) in the ceftriaxone group, but in none in the ciprofloxacin group (p = 0.01). The mean duration of fever was four days in the ciprofloxacin group and about five days in the ceftriaxone group (p = 0.04). In the six patients in the ceftriaxone group who experienced failure, therapy was switched to ciprofloxacin and the patients became afebrile and asymptomatic within 48 hours. Patients with resistant strains of Salmonella typhi and patients with sensitive strains responded equally well to ciprofloxacin therapy. Analysis of a subset of 12 of the multiresistant strains revealed that resistance was encoded for by a transferable 180 kilobase plasmid. Ciprofloxacin represents a useful treatment option in areas where multiresistant strains are likely to be encountered.

Bacteriophage Typing↗

Cefpodoxime - utility in respiratory tract infections and typhoid fever.

Cefpodoxime is a oral third generation cephalosporin active against most of gram positive and gram negative bacteria except Pseudomonas, B. fragilis and Entrococcous. Clinical studies have confirmed efficacy of cefpodoxime in acute otitis media, sinusitis and tosillopharyngitis. Twice daily administration and safety profile increases compliance and decreases failure rate. It has a role as switch over therapy from intravenous ceftriaxone in serious respiratory tract infections (RTIs). In areas where common respiratory pathogens show decreased sensitivity to penicillins and macrolides cefpodoxime can be used as empirical first line therapy in respiratory tract infections. It seems to be a promising molecule in pediatric typhoid fever because of its excellent activity against Salmonella species but clinical trials are limited.

Administration, Oral↗

Ciprofloxacin in typhoid fever.

The study covers 78 children with typhoid fever who were hospitalized in April & May 1990. Serious complications were present in 32% (toxemia 22%, ileus 25% and myocarditis 8%). Blood cultures were positive in 30 of 49 tested. Others were diagnosed by positive Widal test. In vitro cultures of S. typhi were resistant to chloramphenicol (90%), ampicillin (93%) and co-trimoxazole (97%). However all were highly sensitive to ciprofloxacin and moderately sensitive to cephalexin and gentamycin. Ciprofloxacin alone or in combination was given in 73 of the 78 children and found to be remarkably effective in controlling the disease and preventing relapse. No serious side effects were noted. The cohort is being followed up for possible long term adverse effects.

Adolescent↗

Characteristics of lipopolysaccharides of Salmonella typhi isolated from carriers and patients suffering from typhoid fever.

Lipopolysaccharides (LPS) of Salmonella typhi strains, isolated from carriers and patients suffering from typhoid fever, were characterised according to their biochemical properties, morphological structure and degree of aggregation of complexes. All preparations of LPS, regardless of their origin, were morphologically heterogeneous. Free electrophoresis and immunoelectrophoresis demonstrated that LPS preparations were composed of components possessing different mobilities in electric fields. LPS of bacterial strains isolated from both carriers and patients, split upon reaction in immunoelectrophoresis with specific antiserum 73, rabbit antiserum to Salmonella typhi Vi Bhatnagar and 0-901 split into anodic and cathodic fractions. The anodic fraction reacted similarly as Vi antigen. LPS from Salmonella typhi Ty-2 yielded only the cathodic fraction, typical for O antigen. LPS from strains which were passaged twice in nutritional medium possessed identical properties as LPS from fresh cultures of Salmonella typhi. Electron microscopy revealed that LPS appears as long bands, rods, ellipsoid forms and amorphous material. Contrary to amorphous material, the bands, rods and ellipsoid forms possessed three-layer structure.

Antigens, Bacterial↗

Factors effecting morbidity in typhoid intestinal perforation in children.

To determine the factors affecting morbidity in patients with typhoid intestinal perforation (TIP), 42 patients who had been operated upon for TIP between 1990 and 2000 were reviewed. The average age was 10.4 years, the male-to-female ratio 2.5/1. The mean interval from admission to operation was 6 h. Twenty-three children had multiple perforations. Primary closure (PC) was performed in 55% of the patients, ileostomy in 26%, and resection with anastomosis (RA) in 19%. Parenteral nutrition (PN) was available for 22 patients for an average of 9 days. Postoperative complications occurred more commonly in patients with delayed admission and/or severe peritonitis. Hospitalization was shorter and the postoperative complication rate lower in patients who received PN and in those who underwent ileostomy. None of the patients developed an enterocutaneous fistula. The 2 deaths (4.8%) resulted from overwhelming sepsis. The most significant factors affecting morbidity were prolongation of perforation-operation interval and severe peritonitis. No operative procedure is likely to be the best in all cases; therapy should be individualized. Ileostomy appears to be an effective procedure, particularly in patients with severe abdominal contamination and delayed presentation. The use of PN in addition to standard medical and surgical therapy in patients with TIP may be beneficial.

Adolescent↗

Postoperative complications after surgery for typhoid perforation in children in Ghana.

One of the most severe complications of typhoid fever is perforation of the ileum (TPI); it is also a cause of high morbidity and mortality in endemic areas. After surgery for TPI, other complications may set in postoperatively, compounding the problem. A prospective study of 121 children who were operated upon for TPI to identify the postoperative complications showed that the most common was wound infection. The most serious were: mechanical intestinal obstruction, abdominal dehiscence, and enterocutaneous fistulae. Physicians caring for such children should be aware of these complications and their mode of presentation so as to quickly and decisively manage them to prevent more deaths.

Adolescent↗

Typhoid ileal perforation in Nigerian children: an analysis of 106 operative cases.

Typhoid ileal perforation (TP) is a major problem in developing countries and carries a high mortality. The purpose of this retrospective study from Nigeria was to review the outcome in children less than 15 years of age who underwent surgery for TP from 1984 to 1999. Demographic data, clinical features, results of investigations, findings at surgery, postoperative course, and complications were recorded. There were 55 boys and 51 girls. The median age at presentation was 10 years (range 3-14). The surgically confirmed perforation rate was 11.0%. The clinical features in children older than 5 years were similar to already documented patterns in the literature. In children less than 5 years old the predominant symptoms were fever and vomiting only. Therefore, in the very young a high index of suspicion is required to avoid delay in diagnosis. Ninety eight patients (92.5%) had simple double-layer closure of the perforation. The mean hospital stay among survivors was 23.6 +/- 18.8 days. The commonest postoperative complications were wound infection and enterocutaneous fistula. The overall mortality was 23.8%, increasing to 50% in children aged less than 5 years, although the difference was not statistically significant (P > 0.05). To improve survival in TP, attention should be focused on perioperative resuscitation and early intervention. The provision of potable water, adequate sanitation, and active immunisation are means to eradicate the disease.

Adolescent↗

Diagnostic value of bone marrow culture in typhoid fever.

The diagnostic efficacy of bone-marrow culture, serial blood cultures and agglutination tests was compared in a prospective study of 60 patients with typhoid fever, two thirds of whom had received prior antibacterial therapy. Salmonella typhi was recovered from marrow cultures in 95% of patients but blood cultures were positive in only 43.3% (P less than 0.001). Agglutination tests were eventually diagnostic in 56.7% of patients, but in only 25% at the time of admission. If procedures had been limited to blood cultures and agglutination tests, diagnosis would have been missed in 21.7% of cases. The efficacy of marrow cultures was affected not by the duration of disease but by the extent of antibacterial therapy before presentation. Bacteriological recovery was faster from marrow cultures.

Adolescent↗