Trimethoprim and Sulphamethoxazole in Typhoid

Six patients with proved typhoid fever were treated with a combination of trimethoprim and sulphamethoxazole; four others were treated with chloramphenicol. All ten patients made an uneventful recovery.Though the numbers are small it appears that the patients treated with the combined drugs did just as well as those treated with chloramphenicol, and fever seemed to subside quicker with the combined drugs.Trimethoprim and sulphamethoxazole have low toxicities, so further studies of their use in the treatment of typhoid are justified.     

Typhoid outbreak in Kingston,Ont: experience with high-dose oral ampicillin.

Twenty-four children contracted typhoid fever at a summer camp near Kingston, Ont. Six were treated with chloramphenicol alone and 15 with high doses of ampicillin (300 mg/kg-d) by mouth. Ampicillin in this dosage was well tolerated except in three children in whom severe urticarial rashes developed and two who had significant diarrhea. However, high-dose oral ampicillin therapy had no advantage over that with lower doses or over chloramphenicol as judged by the rate of defervescence after the start of treatment, the rate of clinical relapse and the frequency of excretion of Salmonella typhi during convalescence.     

CHLORAMPHENICOL IN THE TREATMENT OF TYPHOID FEVER

Six patients with typhoid fever were treated with chloramphenicol. The excellent clinical response in four cases suggests that chloramphenicol is the drug of choice in the treatment of this disease. In one case in which clinical relapse occurred, there was good response to re-treatment. One patient, critically ill, in a typhoid state, and treated late in the course of the disease, died without beneficial effect from chloramphenicol, but the patient had been unable to retain the drug because of vomiting.     

Trimethoprim and Sulphamethoxazole in Typhoid Fever in Children

One hundred and three children with proved typhoid fever were treated with trimethoprim-sulphamethoxazole, and the results compared with those of a further 40 children treated with chloramphenicol. The bacteriological response to trimethoprim-sulphamethoxazole was unsatisfactory. From this study it seems that at present chloramphenicol is still the treatment of choice for typhoid fever. In view of the haematological changes occurring during therapy with trimethoprim-sulphamethoxazole caution is necessary and monitoring of the blood picture advisable, even at the recommended dose.     

Typhoid fever: facing the challenge of resistant strains

The introduction of chloramphenicol in 1948 revolutionised the outcome of typhoid fever but chloramphenicol-resistant strains of Salmonella enterica serotype Typhi were reported just two years later. Resistance followed also the introduction of ampicillin and co-trimoxazole. During the second half of the 1980s, strains resistant to the three first-line antimicrobial agents, chloramphenicol, ampicillin and co-trimoxazole emerged and spread rapidly throughout the Indian subcontinent and South East Asia. During the 1990s when fluoroquinolones had become a first-line treatment for typhoid fever, these multi drug resistant (MDR) strains acquired an additional resistance to nalidixic acid with decreased susceptibilities to ciprofloxacin (CIPDS) (MIC range, 0.125-1 mg/l). Considerable data have now accumulated to suggest that infections due to CIPDS strains may not respond satisfactorily to therapy with ciprofloxacin or ofloxacin. Furthermore, identification of such CIPDS strains in clinical laboratories is not easy without determination of MIC of ciprofloxacin. Recently, several isolates highly resistant to ciprofloxacin or to extended-spectrum cephalosporins of Asian origin have been reported.     

Molecular characterization of antibiotic resistance in clinical Salmonella typhi isolated in Ghana

Fifty-eight clinical Salmonella typhi strains isolated from patients suspected of suffering from typhoid fever were obtained at the Korle-Bu Teaching Hospital and the Noguchi Memorial Institute for Medical Research, both located in Ghana, Africa. Each isolate was examined for susceptibility to ampicillin, chloramphenicol, streptomycin, tetracycline, and trimethoprim/sulfamethoxazole by the disk diffusion assay. Five of the isolates were resistant to all five antibiotics while 10 isolates were resistant to ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole, which are considered 'first line' antibiotics in the treatment of typhoid fever. Thirty-four isolates were resistant to at least one of the antibiotics tested and 62% of these isolates possessed conjugable plasmids belonging to incompatibility group IncHI. Ninety percent of the conjugable plasmids conferred a multiple drug-resistant phenotype on the strains harboring them. Additionally, 14 strains contained plasmids that were transformable and six of them encoded multiple drug resistance. Our findings indicate that multiple drug resistance to the 'first line' antibiotics in S. typhi may be more prevalent in Africa than previously thought.     

Mecillinam: a new antibiotic for enteric fever.

Mecillinam is a new antibiotic related to the penicillins but more active than ampicillin against salmonellae, including Salmonella typhi. Mecillinam must be administered parenterally, but the ester, pivmecillinam, is absorbed from the gut. Eight patients suffering from typhoid fever and one suffering from paratyphoid fever were treated with the antibiotic, and seven responded satisfactorily. One patient could not tolerate pivmecillinam because of vomiting but there were no other adverse reactions. Serum and bile levels of mecillinam were many times the minimum inhibitory concentrations for most salmonellae. The antibiotic is a promising addition to the agents available for treating typhoid.     

Prevalence of multi-drug resistant Salmonella typhi among clinically diagnosed typhoid fever patients in Lagos, Nigeria

A total of 635 clinically diagnosed typhoid fever patients were bled from three different health institutions in the metropolis of Lagos, Nigeria over a period of 15 months, May 1997 to July 1998. Out of the total blood cultured, 101 (15.9%) isolates of Salmonella species were isolated of which 68 (67.3%) were S. typhi, 17 (16.8%) and 16 (15.8%) were S. paratyphi A. and S. arizonae respectively. The overall isolation rate of S. typhi among patients is 10.7%, with most isolates 45.9% found among the severely-ill young adults, age group 16-30 years. All isolates were subjected to anti-microbial susceptibility testing using 12 different antibiotics: chloramphenicol, ampicillin, cotrimoxazole, gentamicin, colistin sulfate, nalidixic acid, nitrofurantoin, cefotaxime, tetracycline, streptomycin, ofloxacin and ciprofloxacin. All the S. typhi and S. paratyphi A isolates showed resistance to two or more of the 10 of 12 antibiotics tested particularly the 3-first-line antibiotics commonly used (chloramphenicol, ampicillin and cotrimoxazole) in the treatment of typhoid fever in Nigeria. No isolate showed resistance to ofloxacin and ciprofloxacin, however, nalidixic acid and gentamicin showed a moderate and appreciable inhibition to most of our isolates.     

Development of specific cellular immunoreactivity in typhoid fever.

Development of cellular immunoreactivity to Salmonella typhi and Salmonella paratyphi-A was studied by the leukocyte migration inhibition test in 9 patients with typhoid fever and in 2 patients with paratyphoid fever. Cellular reactivity could be demonstrated from the first days of the disease in all the subjects. The most pronounced migration inhibition was observed during the febrile period. It is suggested that specific cellular reactivity may play a pathogenetic role in typhoid fever.     

Problems of etiotropic therapy of typhoid fever and approaches to their solution]

The main problems of etiotropic therapy for typhoid fever lie in underestimate of the characteristic features of its pathogenesis and particularly in development of typhoid granulomas and their histogenesis, as well as in wide spread of typhoid fever pathogenic strains resistant to the routine chemotherapeutics, i.e. polyresistant strains. Some problems are due to incorrect choice of the antimicrobials and their combinations, optimal doses, administration routes and pathogenetic therapy. In the XXth centure an increase in the emergence and a change in the nature of the typhoid fever pathogen resistance to antimicrobials were observed. It was shown that from the pharmacologic and pharmacodynamic viewpoints the highest efficacy of typhoid fever therapy should be provided by the following antimicrobials: fluoroquinolones (except for norfloxacin), 3rd and 4th generation cephalosporins, aminopenicillins, chloramhenicol (levomycetin), combinations of 2nd and 3rd generation aminoglycosides with biseptol, aminopenicillins or doxycycline, as well as chloramphenicol combinations with aminopenicillins or 2nd to 4th generation cephalosporins. Practical recommendations for the etiotropic therapy of patients with typhoid fever during its outbreak or epidemic are presented.     

Comparative trial of Co-trimoxazole and Chloramphenicol in Typhoid Fever

A comparative trial of co-trimoxazole and chloramphenicol was conducted in two groups of 50 patients each to try to resolve conflicting opinions on the relative merits of the two drugs in the treatment of typhoid fever. We conclude that in our part of India co-trimoxazole is superior to chloramphenicol and that differences in our findings to those of others may perhaps be accounted for by differences in strains of Salmonella typhi, ethnic differences, and possibly differences in herd immunity to typhoid.     

Clinical and bacteriological profiles of patients with typhoid fever treated during 1975-1998 in the Tokyo Metropolitan Komagome Hospital

Patients with typhoid fever presenting to the Tokyo Metropolitan Komagome Hospital during the period 1975-1998 were retrospectively investigated. All cases were diagnosed by a positive culture for Salmonella typhi in either of their clinical specimens. Of the total number of 130 patients, 57% contracted the disease abroad; this population increased in later years as the total numbers of cases decreased. The period from disease onset to diagnosis averaged 14 days with 20% of the cases requiring over three weeks to establish a diagnosis. As for symptomatology relative bradycardia was seen in less than half of the cases, and rose spots or splenomegaly in less than one third. A positive blood culture was the most frequent test establishing the diagnosis followed by a positive stool culture. Intestinal bleeding was recognized in as many as 35 cases (27%) and even intestinal perforation occurred in two cases (1.5%). Chloramphenicol was most commonly employed during the early study period, however, during the late period it was replaced by fluoroquinolones. The clinical cure rate was 98% with regimens that include fluoroquinolones/quinolone; however it was 87% with the other antimicrobial regimens. Bacteriological relapse occurred in 25% of the non-fluoroquinolone group while only in 2.0% in the fluoroquinolone/quinolone group. Four strains of Salmonella typhi that were multi-resistant to chloramphenicol, ampicillin and cotrimoxazole were isolated in travelers from Asia. Early diagnosis by appropriate bacteriological examination regardless of classical symptomatology should be stressed and the use of fluoroquinolones is warranted in the treatment of typhoid fever.     

Acute renal failure in tropical Africa.

Between 1972 and 1975, 55 adult patients with acute renal failure were admitted to the renal unit of Korle Bu Hospital. Fourteen patients died, giving an overall death rate of 25%. Massive intravascular haemolysis after a short febrile illness was the commonest cause of acute renal failure. Clinically these patients presented with blackwater fever but in only one could Plasmodium falciparum malaria be confidently diagnosed. In half the patients various bacterial and viral infections (especially typhoid) could be incriminated as causing this blackwater fever syndrome. The incidence of glucose-6-phosphate dehydrogenase deficiency was 22.5%, but we could not confirm the impression of a greater predisposition to acute renal failure in patients with this enzyme defect.     

Clinical and Epidemiological Features of Typhoid Fever in Pemba,Zanzibar: Assessment of the Performance of the WHO Case Definitions

Background

The gold standard for diagnosis of typhoid fever is blood culture (BC). Because blood culture is often not available in impoverished settings it would be helpful to have alternative diagnostic approaches. We therefore investigated the usefulness of clinical signs, WHO case definition and Widal test for the diagnosis of typhoid fever.

Methodology/Principal Findings

Participants with a body temperature ≥37.5°C or a history of fever were enrolled over 17 to 22 months in three hospitals on Pemba Island, Tanzania. Clinical signs and symptoms of participants upon presentation as well as blood and serum for BC and Widal testing were collected. Clinical signs and symptoms of typhoid fever cases were compared to other cases of invasive bacterial diseases and BC negative participants. The relationship of typhoid fever cases with rainfall, temperature, and religious festivals was explored. The performance of the WHO case definitions for suspected and probable typhoid fever and a local cut off titre for the Widal test was assessed. 79 of 2209 participants had invasive bacterial disease. 46 isolates were identified as typhoid fever. Apart from a longer duration of fever prior to admission clinical signs and symptoms were not significantly different among patients with typhoid fever than from other febrile patients. We did not detect any significant seasonal patterns nor correlation with rainfall or festivals. The sensitivity and specificity of the WHO case definition for suspected and probable typhoid fever were 82.6% and 41.3% and 36.3 and 99.7% respectively. Sensitivity and specificity of the Widal test was 47.8% and 99.4 both forfor O-agglutinin and H- agglutinin at a cut-off titre of 1∶80.

Conclusions/Significance

Typhoid fever prevalence rates on Pemba are high and its clinical signs and symptoms are non-specific. The sensitivity of the Widal test is low and the WHO case definition performed better than the Widal test.     

Neurologic Manifestations Associated with an Outbreak of Typhoid Fever, Malawi - Mozambique, 2009: An Epidemiologic Investigation

Background

The bacterium Salmonella enterica serovar Typhi causes typhoid fever, which is typically associated with fever and abdominal pain. An outbreak of typhoid fever in Malawi-Mozambique in 2009 was notable for a high proportion of neurologic illness.

Objective

Describe neurologic features complicating typhoid fever during an outbreak in Malawi-Mozambique

Methods

Persons meeting a clinical case definition were identified through surveillance, with laboratory confirmation of typhoid by antibody testing or blood/stool culture. We gathered demographic and clinical information, examined patients, and evaluated a subset of patients 11 months after onset. A sample of persons with and without neurologic signs was tested for vitamin B6 and B12 levels and urinary thiocyanate.

Results

Between March – November 2009, 303 cases of typhoid fever were identified. Forty (13%) persons had objective neurologic findings, including 14 confirmed by culture/serology; 27 (68%) were hospitalized, and 5 (13%) died. Seventeen (43%) had a constellation of upper motor neuron findings, including hyperreflexia, spasticity, or sustained ankle clonus. Other neurologic features included ataxia (22, 55%), parkinsonism (8, 20%), and tremors (4, 10%). Brain MRI of 3 (ages 5, 7, and 18 years) demonstrated cerebral atrophy but no other abnormalities. Of 13 patients re-evaluated 11 months later, 11 recovered completely, and 2 had persistent hyperreflexia and ataxia. Vitamin B6 levels were markedly low in typhoid fever patients both with and without neurologic signs.

Conclusions

Neurologic signs may complicate typhoid fever, and the diagnosis should be considered in persons with acute febrile neurologic illness in endemic areas.     

Typhoid Outbreak in Songkhla,Thailand 2009–2011: Clinical Outcomes,Susceptibility Patterns,and Reliability of Serology Tests

Objective

To determine the clinical manifestations and outcomes, the reliability of Salmonella enterica serotype Typhi (S ser. Typhi) IgM and IgG rapid tests, and the susceptibility patterns and the response to treatment during the 2009–2011 typhoid outbreak in Songkhla province in Thailand.

Method

The medical records of children aged <15 years with S ser. Typhi bacteremia were analysed. The efficacy of the typhoid IgM and IgG rapid tests and susceptibility of the S ser. Typhi to the current main antibiotics used for typhoid (amoxicillin, ampicillin, cefotaxime, ceftriaxone, co-trimoxazole, and ciprofloxacin), were evaluated.

Results

S ser. Typhi bacteremia was found in 368 patients, and all isolated strains were susceptible to all 6 antimicrobials tested. Most of the patients were treated with ciprofloxacin for 7–14 days. The median time (IQR) of fever before treatment and duration of fever after treatment were 5 (4, 7) days and 4 (3, 5) days, respectively. Complications of ascites, lower respiratory symptoms, anemia (Hct <30%), and ileal perforation were found in 7, 7, 22, and 1 patients, respectively. None of the patients had recurrent infection or died. The sensitivities of the typhoid IgM and IgG tests were 58.3% and 25.6% respectively, and specificities were 74.1% and 50.5%, respectively.

Conclusion

Most of the patients were diagnosed at an early stage and treated with a good outcome. All S ser. Typhi strains were susceptible to standard first line antibiotic typhoid treatment. The typhoid IgM and IgG rapid tests had low sensitivity and moderate specificity.     

Listeriosis at Vancouver General Hospital, 1965-79.

The records were reviewed of all patients treated at the Vancouver General Hospital over the 15 years from 1965 through 1979 for infections proved by culture to have been caused by Listeria monocytogenes. Although listeriosis is not common in humans, certain groups seem to be susceptible - immunocompromised patients, pregnant women, neonates and the elderly. All these groups were represented among the 22 cases reviewed. There were 17 adults, 3 of whom were pregnant women who had only a mild influenza-like illness. Of the remaining 14 adults 9 were immunocompromised and 5 apparently immunocompetent; 7 presented with meningitis and 7 with bacteremia only. Of the five infants with neonatal listeriosis, two had early-onset disease (bacteremia) and three had the late-onset form (meningitis). Seven patients were treated with penicillin alone, seven with ampicillin alone and eight with penicillin or ampicillin combined with kanamycin, gentamicin or chloramphenicol. There were eight deaths: several were directly attributable to the listeriosis, but in others the severity of the underlying illness was an important factor. Serotypes 1 and 4b were equally common among the 16 specimens of L. monocytogenes that were typed.     

Facility-based disease surveillance and Bayesian hierarchical modeling to estimate endemic typhoid fever incidence,Kilimanjaro Region,Tanzania, 2007–2018

Growing evidence suggests considerable variation in endemic typhoid fever incidence at some locations over time, yet few settings have multi-year incidence estimates to inform typhoid control measures. We sought to describe a decade of typhoid fever incidence in the Kilimanjaro Region of Tanzania. Cases of blood culture confirmed typhoid were identified among febrile patients at two sentinel hospitals during three study periods: 2007–08, 2011–14, and 2016–18. To account for under-ascertainment at sentinel facilities, we derived adjustment multipliers from healthcare utilization surveys done in the hospital catchment area. Incidence estimates and credible intervals (CrI) were derived using a Bayesian hierarchical incidence model that incorporated uncertainty of our observed typhoid fever prevalence, of healthcare seeking adjustment multipliers, and of blood culture diagnostic sensitivity. Among 3,556 total participants, 50 typhoid fever cases were identified. Of typhoid cases, 26 (52%) were male and the median (range) age was 22 (<1–60) years; 4 (8%) were aged <5 years and 10 (20%) were aged 5 to 14 years. Annual typhoid fever incidence was estimated as 61.5 (95% CrI 14.9–181.9), 6.5 (95% CrI 1.4–20.4), and 4.0 (95% CrI 0.6–13.9) per 100,000 persons in 2007–08, 2011–14, and 2016–18, respectively. There were no deaths among typhoid cases. We estimated moderate typhoid incidence (≥10 per 100 000) in 2007–08 and low (<10 per 100 000) incidence during later surveillance periods, but with overlapping credible intervals across study periods. Although consistent with falling typhoid incidence, we interpret this as showing substantial variation over the study periods. Given potential variation, multi-year surveillance may be warranted in locations making decisions about typhoid conjugate vaccine introduction and other control measures.     

Antibiotic sensitivity of S. typhi cultures that have reverted from L forms isolated from the blood of patients]

L-forms of bacteria were isolated in 18 out of 300 fever patients with diagnoses of typhoid-paratyphoid fever, grippe, virus respiration disease and others in the Diagnostic Department of an Infection Hospital during bacteriological tests of the blood. Among the cultures tested 13 were instable and reversed to the bacterial form. The type identification showed that only 9 revertants possessed properties characteristic of the typhoid fever microbes and belonged to S. typhi. Sensitivity of the typhoid fever revertants to levomycetin, sintomycin, streptomycin, pencillin and tetracycline was studied. The studies showed that the typhoid fever revertants from the L-forms isolated from the patients were sufficiently sensitive to levomycetin, sintomycin, penicillin and tetracycline. The minimum bactericidal concentrations of the above antibiotics ranged within 12.5--100 gamma/ml.     

Assessment of the efficacy of treating infections in hematopoietic proliferative diseases: Monotherapy with ceftazidime and tobramycin combined with amoxycillin/ampicillin

Efficacy of the ceftazidime monotherapy in 120 febrile children with neoplastic diseases and granulocytopenia was compared with that of tobramycin combined with amoxycillin/ampicillin. The obtained results were similar in both types of antibiotic therapy. However, granulocytopenia was higher and septicemia was more frequent in children treated with ceftazidime. Isolated bacteria were more sensitive to ceftazidime than to tobramycin with amoxycillin/ampicillin. Both regimens were tolerated well. Despite a low number of patients in both groups, one may conclude that ceftazidime is more efficient in patients with granulocytopenia. Less adverse reactions, lower number of infections, less frequent medical procedures, elimination of the potentially toxic aminoglycosides and lower cost of therapy advocate the use of ceftazidime monotherapy.