Typhoid fever--important issues still remain.
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Anti-Bacterial Agents↗
Biomedical subjects
J Wain
Publications and source records attributed to J Wain.
Penicillin vs. erythromycin in the treatment of diphtheria.
In an open-label, randomized trial, 44 Vietnamese children with diphtheria were given penicillin therapy (intramuscular benzylpenicillin, 50,000 U/[kg.d] for 5 days and then oral penicillin, 50 mg/[kg.d] for 5 days), and 42 were given erythromycin therapy (50 mg/[kg.d] orally for 10 days). There were no differences in times to membrane clearance or bacteriologic clearance, but median times to fever clearance were 27 hours (95% confidence interval [CI], 19-30; range, 0-124 hours) for penicillin recipients and 46 hours (95% CI, 34-54; range, 0-148 hours) for erythromycin recipients (P = .0004). In the penicillin group, acute treatment failed for one patient, and one patient relapsed. Three patients in the penicillin group developed diphtheritic myocarditis as evidenced by abnormal electrocardiograms. Erythromycin did not cause prolongation of the QT interval corrected for heart rate. Cultures of specimens from 15 patients (17.4%) were positive for toxigenic Corynebacterium diphtheriae. All isolates were susceptible to penicillin, but for isolates (27%), all of which were from patients who received penicillin treatment, were resistant to erythromycin (minimum inhibitory concentrations, > 64 mg/L). Penicillin is recommended as first-line treatment for diphtheria in Vietnam.
Adolescent↗
Quantitation of bacteria in blood of typhoid fever patients and relationship between counts and clinical features, transmissibility, and antibiotic resistance.
Salmonella typhi was isolated from 369 and Salmonella paratyphi A was isolated from 6 of 515 Vietnamese patients with suspected enteric fever. Compared with conventional broth culture of blood, direct plating of the buffy coat had a diagnostic sensitivity of 99.5% (95% confidence interval [CI], 97.1 to 100%). Blood bacterial counts were estimated by the pour plate method. The median S. typhi count in blood was 1 CFU/ml (range, <0.3 to 387 CFU/ml), of which a mean of 63% (95% CI, 58 to 67%) were intracellular. The mean number of bacteria per infected leukocyte was 1.3 (interquartile range [IQR], 0.7 to 2.4) CFU/cell (n = 81). Children (< 15 years old; n = 115) had higher median blood bacterial counts than adults (n = 262): 1.5 (range, <0.3 to 387) versus 0.6 (range, <0.3 to 17.7) CFU/ml (P = 0.008), and patients who excreted S. typhi in feces had higher bacteremias than those who did not: a median of 3 (range, <0.3 to 32) versus 1 (range, <0.3 to 68) CFU/ml (P = 0.02). Blood bacterial counts declined with increasing duration of illness (P = 0.002) and were higher in infections caused by multidrug-resistant S. typhi (1.3 [range, <0.3 to 387] CFU/ml; n = 313) than in infections caused by antibiotic-sensitive S. typhi (0.5 [range, <0.3 to 32] CFU/ml; n = 62) (P = 0.006). In a multivariate analysis this proved to be an independent association, suggesting a relationship between antibiotic resistance and virulence in S. typhi.
Adolescent↗
Genetic epidemiology of severe, early-onset chronic obstructive pulmonary disease. Risk to relatives for airflow obstruction and chronic bronchitis.
Severe alpha-1-antitrypsin deficiency is the only proven genetic risk factor for chronic obstructive pulmonary disease (COPD). We have assembled a cohort of 44 probands with severe, early-onset COPD, who do not have severe alpha-1-antitrypsin deficiency. A surprisingly high prevalence of females (79.6%) was found. Assessment of the risk to relatives of these early-onset COPD probands for airflow obstruction and chronic bronchitis was performed to determine whether significant familial aggregation for COPD, independent of alpha-1-antitrypsin deficiency, could be demonstrated. First- degree relatives of early-onset COPD probands had significantly lower FEV1 and FEV1/FVC values than control subjects (p < 0.01), despite similar pack-years of smoking. Reduced spirometric values in first-degree relatives of early-onset COPD probands were found only in current or ex-cigarette smokers. The mean FEV1 in current or ex-smoking first-degree relatives was 76.1 +/- 20.9% predicted compared to 89.2 +/- 14.4% predicted in current or ex-smoking control subjects (p < 0.01); in lifelong nonsmokers, the mean FEV1 was 93.4% predicted for both control subjects and first-degree relatives of early-onset COPD probands. Generalized estimating equations, adjusting for age and pack-years of smoking, demonstrated increased odds of reduced FEV1 and chronic bronchitis in current or ex-smoking first-degree relatives of early-onset COPD probands. Using a new method to estimate relative risk from relative odds, we estimate that the relative risks for FEV1 below 60%, FEV1 below 80%, and chronic bronchitis are each approximately three in current or ex-smoking first-degree relatives of early-onset COPD probands. The increased risk to relatives of early-onset COPD probands for reduced FEV1 and chronic bronchitis, limited to current or ex-smokers, suggests genetic risk factor(s) for COPD that are expressed in response to cigarette smoking.
Bronchitis↗
Quinolone-resistant Salmonella typhi in Viet Nam: molecular basis of resistance and clinical response to treatment.
Nalidixic acid-resistant Salmonella typhi (NARST) was first isolated in Viet Nam in 1993. Analysis of the quinolone resistance-determining region of gyrA in 20 NARST isolates by polymerase chain reaction and single-stranded conformational polymorphism yielded two novel patterns: pattern II corresponding to a point mutation at nucleotide 87 Asp-->Gly (n = 17), and pattern III corresponding to a point mutation at nucleotide 83 Ser-->Phe (n = 3). In trials of short-course ofloxacin therapy for uncomplicated typhoid, 117 (78%) of 150 patients were infected with multidrug-resistant S. typhi, 18 (15%) of which were NARST. The median time to fever clearance was 156 hours (range, 30-366 hours) for patients infected with NARST and 84 hours (range, 12-378 hours) for those infected with nalidixic acid-susceptible strains (P < .001). Six (33.3%) of 18 NARST infections required retreatment, whereas 1 (0.8%) of 132 infections due to susceptible strains required retreatment (relative risk = 44; 95% confidence interval = 5.6-345; P < .0001). We recommend that short courses of quinolones not be used in patients infected with NARST.
4-Quinolones↗
Potential impact on survival of improved tumor downstaging and resection rate by preoperative twice-daily radiation and concurrent chemotherapy in stage IIIA non-small-cell lung cancer.
PURPOSE: The main objectives of this study were (a) to ascertain the feasibility and toxicity of preoperative twice-daily radiation therapy and concurrent chemotherapy, surgery, and postoperative therapy in stage IIIA (N2) non-small-cell lung cancer (NSCLC), and (b) to evaluate tumor response, resection rate, pathologic tumor downstaging, and survival. METHODS: Eligibility included biopsy-proven N2 lesion (stage IIIA) by mediastinoscopy, Karnofsky performance score > or = 70, and weight loss less than 5% in the 3 months before diagnosis. The treatment program consisted of two courses of preoperative cisplatin, vinblastine, and fluorouracil (5-FU); 42 Gy concurrent radiation at 1.5 Gy per fraction in two fractions per day; surgery on day 57; and one more course of postoperative chemotherapy and 12 to 18 Gy of concurrent twice-daily radiation. RESULTS: Forty-two patients with stage IIIA (N2) NSCLC (27 men and 15 women, age 38 to 77 years) were enrolled onto this prospective study. Forty of 42 patients tolerated the intended dose (42 Gy) of preoperative radiation and 37 of 39 resected patients received prescribed postoperative radiation. The intended dose of chemotherapy was given in 100%, 70%, and 60% of patients for the first, second, and third courses of chemotherapy. Marked dysphagia that required intravenous hydration was noted in 14% of patients (six of 42). Myelotoxicities included grade > or = 3 granulocytopenia in 23% and thrombocytopenia in 6% of 113 chemotherapy courses. Febrile neutropenia that required hospital admission was noted in 9% of 113 chemotherapy courses. Surgical resection was performed in 93% of patients. Treatment-related mortality was noted in 7% of patients. The overall survival rates by the Kaplan-Meier method were 66%, 37%, and 37% at 2,3, and 5 years, respectively, with a median follow-up time of 48 months. Pathologic examination of the surgical specimen showed a downward shift in tumor extent from stage IIIA (N2) to stage II (N1) in 33%, to stage I (NO) in 24% (10 of 42), and to stage 0 (TONO) in 9.5%, for a total of 67%. The degree of tumor downstaging was also translated into a survival benefit: 5-year survival rates from the time of surgery were 79%, 42%, and 18% for postoperative tumor stages 0 and I, II, and III, respectively (P = .04). CONCLUSION: Concurrent chemoradiotherapy using twice-daily radiation is an effective induction regimen that resulted in 67% tumor downstaging, and an encouraging 37% 5-year survival rate. The degree of tumor downstaging may be a useful intermediate end point for survival benefit in stage IIIA (N2) NSCLC.
Adult↗
Preoperative predictors of operative morbidity and mortality in COPD patients undergoing bilateral lung volume reduction surgery.
Bilateral volume reduction surgery (VRS) improves lung function for selected patients with emphysema. However, predictors of outcome are not well defined. We reviewed the preoperative characteristics of the first 47 consecutive patients who underwent bilateral VRS at the Massachusetts General Hospital in order to define potential predictors of unacceptable outcome. Preoperative data included spirometry, plethysmography, diffusion of carbon monoxide (Dco), maximum inspiratory pressure (MIP), maximum expiratory pressure, resting arterial blood gases (ABG), cardiopulmonary exercise testing with ABG and lactate sampling, and radionuclide ventriculography. Prepulmonary and postpulmonary rehabilitation 6-min walk tets (6MWT), and preoperative chest CT scans were also obtained. Twenty-two subjects were male and 17 of the subjects were on the lung transplant list. Patient characteristics included age of 60.5 +/- 7.5 years, FEV1 of 0.67 +/- 0.20 L, total lung capacity of 7.56 +/- 1.7 L, Dco of 7.40 +/- 4.1 mL/min/mm Hg, and PaCO2 of 41.6 +/- 6.4 mm Hg (mean +/- SD). The FEV1, vital capacity, MIP, resting room air PaCO2, prepulmonary and postpulmonary rehabilitation 6MWT, and PaCO2 at maximum oxygen consumption correlated with length of hospitalization (p < 0.05). Based on analysis of 41 of 47 patients for whom there were complete data, the inability to walk more than 200 m on the 6MWT before or after preoperative pulmonary rehabilitation, and resting PaCO2 > or = 45 mm Hg were the best predictors of an unacceptable outcome. If either of these characteristics was present, six of 16 vs zero of 25 died (Fisher's Exact Test, p = 0.0025, one-tailed) and 11 of 16 vs four of 25 had hospital courses > 21 days (p < 0.002). Both the 6MWT < 200 m and resting PaCO2 > or = 45 mm Hg alone correlated with death (p = 0.004 and p = 0.012, respectively) and the resting PaCO2 > or = 45 mm Hg correlated with hospital days > 21 (p = 0.0002). In conclusion, the data suggest that the inability to walk at least 200 m in 6 min before or after pulmonary rehabilitation and a resting room air PaCO2 > or = 45 mm Hg are excellent preoperative predictors of unacceptable postoperative outcomes.
Exercise Test↗
Two or three days of ofloxacin treatment for uncomplicated multidrug-resistant typhoid fever in children.
An open randomized comparison of 2 days (Ofx2) versus 3 days (Ofx3) of oral ofloxacin treatment (15 mg/kg/day) was conducted with Vietnamese children between 1 and 15 years of age with suspected typhoid fever. Of 108 children enrolled, 100 were blood culture positive for Salmonella typhi, and 86% of the isolates were multidrug resistant. There were no significant adverse effects. The therapeutic responses were similar in both groups, with mean (+/- standard deviation) fever clearances of 107 +/- 60 h in the Ofx3 group and 100 +/- 64 h in the Ofx2 group (P > 0.2). There were six "clinical" failures in the Ofx2 group and two clinical failures in the Ofx3 group (P > 0.2), in which fever and symptoms persisted for more than 1 week after the start of treatment, but only one of these was culture positive (Ofx3). There was one suspected relapse, and one carrier was identified. Short courses of ofloxacin are simple, inexpensive, safe, and effective for the treatment of uncomplicated multidrug-resistant typhoid fever.
Adolescent↗
In vitro antimicrobial susceptibilities of strains of Yersinia pestis.
The in vitro activities of 14 antimicrobial agents were determined for 78 strains of Yersinia pestis. The most active antibiotics were ceftriaxone and ciprofloxacin, followed by ofloxacin and ampicillin. The agents traditionally used for the treatment of plague (streptomycin, tetracycline, and chloramphenicol) were considerably less active. Azithromycin showed poor activity against all strains.
Anti-Bacterial Agents↗
The relationship of the 6-min walk test to maximal oxygen consumption in transplant candidates with end-stage lung disease.
STUDY OBJECTIVE: To assess the relationship of distance ambulated during the 6-min walk test (6'WT) to maximal oxygen consumption (VO2 max). DESIGN: Multivariate analysis of patient characteristics to VO2 max. SETTING: Pre-lung transplant evaluation. PATIENTS: 60 patients (22 men, 38 women; mean age, 44 years) with end-stage lung disease (mean FEV1 and forced vital capacity of 0.97 and 1.93, respectively). MEASUREMENTS AND RESULTS: The 6'WT was performed on a level hallway surface, and VO2 max was obtained during maximal cycle ergometry exercise testing with respiratory gas analysis. Multivariate analysis of patient characteristics (age, sex, weight, FEV1, FVC, diffusing capacity for carbon monoxide (DCO), 6'WT distance ambulated, number of rests per 6'WT, and the maximal heart rate, blood pressure, rate-pressure product, respiratory rate, oxygen saturation, rating of perceived exertion, and amount of supplemental oxygen used during the 6'WT) was performed on two groups of 30 patients each (group A or B) who were randomly assigned to either group by a process of random selection using a computer-generated random numbers program. Distance ambulated was the strongest independent predictor of VO2 max (r = 0.73; p < 0.0001) in both groups, and adding age, weight, and pulmonary function test results (FVC, FEV1, and DCO) to the regression equation increased the correlation coefficient to 0.83. Because of the significant correlation of distance ambulated during the 6'WT to VO2 max, the prediction equation obtained from the multivariate analysis of group A, VO2 max = 0.006 x distance (feet) +3.38, was used to estimate the VO2 max of the group B patients. No significant difference was observed between the estimated (x +/- SD = 8.9 +/- 2.4 mL/kg/min) and observed (x +/- SD = 9.4 +/- 3.8 mL/kg/min) VO2 max (mean difference, 0.5 mL/kg/min; SD of the difference = 2.88). CONCLUSIONS: The distance ambulated during a 6'WT can predict VO2 max in patients with end-stage lung disease. The addition of several patient characteristics can increase the ability to predict VO2 max and account for more of the variability. Such information is valuable when assessing patient response to therapeutic intervention if respiratory gas analysis is unavailable or impractical.
Blood Gas Analysis↗
Short course of ofloxacin for treatment of multidrug-resistant typhoid.
In recent years, multiresistant strains of Salmonella typhi have emerged in many tropical countries. These strains remain highly sensitive to the fluoroquinolone antibiotics, although use of these drugs by children is considered contraindicated because of their reported toxicity in the cartilage of experimental animals. In a paired, open, randomized study during an epidemic of multidrug-resistant typhoid in southern Vietnam, two short-course ofloxacin regimens (15 mg/kg daily for 3 days and 10 mg/kg daily for 5 days) were compared for the treatment of uncomplicated typhoid fever. Of 438 patients enrolled (of whom 286 were < or = 14 years old), 228 had blood cultures positive for Salmonella species (S. typhi, 207; S. paratyphi A, 19; and S. choleraesuis, 2). There was one treatment failure in a patient who took only one dose of ofloxacin. Otherwise, both regimens were completely effective; there were no proven carriers, and there was no evidence of toxicity, particularly in children. A 3-day course of ofloxacin proved to be safe and highly effective in the treatment of uncomplicated, multidrug-resistant typhoid fever.
Adolescent↗
Comparison of ofloxacin and ceftriaxone for short-course treatment of enteric fever.
An open, randomized comparison of ofloxacin (200 mg, every 12 h) given orally for 5 days and ceftriaxone (3 g, once daily) given intravenously for 3 days in the treatment of uncomplicated enteric fever was conducted in Ho Chi Minh City, Vietnam. Salmonella paratyphi type A was isolated from six patients. Salmonella typhi was isolated from 41 patients; 63% of these isolates were resistant to multiple antibiotics: ampicillin, chloramphenicol, sulfamethoxazole, trimethoprim, and tetracycline. Of the culture-confirmed cases, treatment with ofloxacin resulted in complete cure of all 22 patients, whereas 18 of 25 patients treated with ceftriaxone were completely cured (P < 0.01). In the ceftriaxone group, there were six acute treatment failures and one relapse. Mean +/- standard deviation fever clearance times were 81 +/- 25 h for ofloxacin and 196 +/- 87 h for ceftriaxone (P < 0.0001). Short-course treatment with oral ofloxacin (5 days) is significantly better than that with ceftriaxone (3 days) and will be of particular benefit in areas where multiresistant strains of S. typhi are encountered.
Adolescent↗
Inhaled nitric oxide reverses pulmonary vasoconstriction in the hypoxic and acidotic newborn lamb.
We determined whether inhaling low levels of nitric oxide (NO) gas could selectively reverse hypoxic pulmonary vasoconstriction in the near-term newborn lamb and whether vasodilation would be attenuated by respiratory acidosis. To examine the mechanism of air and NO-induced pulmonary vasodilation soon after birth, we measured plasma and lung cGMP levels in the newly ventilated fetal lamb. Breathing at FIO2 0.10 nearly doubled the pulmonary vascular resistance index in newborn lambs and decreased pulmonary blood flow primarily by reducing left-to-right blood flow through the ductus arteriosus. Inhaling 20 ppm NO at FIO2 0.10 completely reversed hypoxic pulmonary vasoconstriction within minutes. Maximum pulmonary vasodilation occurred during inhalation of > or = 80 ppm NO. Breathing 8% CO2 at FIO2 0.10 elevated the pulmonary vascular resistance index to a level similar to breathing at FIO2 0.10 without added CO2. Respiratory acidosis did not attenuate pulmonary vasodilation by inhaled NO. In none of our studies did inhaling NO produce systemic hypotension or elevate methemoglobin levels. Four minutes after initiating ventilation with air in the fetal lamb lung, cGMP concentration nearly doubled without changing preductal plasma cGMP concentration. Ventilation with 80 ppm NO at FIO2 0.21 increased both lung and preductal plasma cGMP concentration threefold. Our data suggest that inhaled NO gas is a rapid and potent selective vasodilator of the newborn pulmonary circulation with an elevated vascular tone due to hypoxia and respiratory acidosis that acts by increasing lung cGMP concentration.
Acidosis, Respiratory↗
Treatment of bacillary dysentery in Vietnamese children: two doses of ofloxacin versus 5-days nalidixic acid.
Nalidixic acid (NA: 55 mg/kg daily for 5 days) is the recommended treatment for uncomplicated bacillary dysentery in areas where multidrug-resistant Shigella are prevalent. An open randomized comparison of this NA regimen with 2 doses of ofloxacin (total 15 mg/kg) was conducted in 1995/96 in 135 Vietnamese children with fever and bloody diarrhoea. Sixty-six children with a bacterial pathogen isolated were eligible for analysis. Of the 63 Shigella isolates, 39 (62%) were resistant to multiple antibiotics. Resolution times for fever and diarrhoea were similar in the 2 groups, but excretion time of stool pathogen was significantly longer in the NA recipients [median (range) days 1 (1-9) vs 1 (1-2), P = 0.001]. There were 9 (25%) treatment failures in the NA regimen and 3 (10%) in the ofloxacin group; P = 0.1. Two patients had NA-resistant Shigella flexneri. One of these isolates was selected during NA treatment. From a clinical and public health standpoint a 2-dose regimen of ofloxacin is preferable to nalidixic acid in the treatment of bacillary dysentery.
Adolescent↗
Risk factors for typhoid fever in the Mekong delta, southern Viet Nam: a case-control study.
In order to identify risk factors for typhoid fever in a highly endemic area, we undertook a case-control study in the Mekong delta, Viet Nam. Cases were 144 consecutive patients admitted to hospital with blood culture-confirmed typhoid fever. Two controls (1 in the hospital and 1 in the community) were chosen for each case. Standardized interviews were conducted with questions regarding recent contact with a typhoid fever patient, eating habits, hygiene and socio-economic level. Cases were more likely to have been in contact with a patient with typhoid fever than hospital controls (adjusted odds ratio (OR) = 5.2, 95% confidence interval (95% CI) 1.7-15.9) or community controls (adjusted OR = 11.9, 95% CI 2.3-60.7); 11% and 14% of typhoid fever cases (compared to hospital or community controls, respectively) were attributable to recent contact with a patient with this disease. These findings suggest that strategies directed towards the persons in contact with a patient might reduce the incidence of secondary cases of typhoid fever.
Adolescent↗
Short courses of ofloxacin for the treatment of enteric fever.
Typhoid fever continues to be a major public health problem in tropical countries, exacerbated in recent years by the spread of multi-drug resistant strains of Salmonella typhi. Short treatment courses of fluoroquinolones are effective, and have the advantage of reduced cost and increased compliance, but the optimal length of treatment is unknown. In an open, randomized comparison, 107 adults with uncomplicated enteric fever (95 of whom had positive blood cultures for S. typhi and 5 for S. paratyphi) were treated with oral ofloxacin, 15 mg/kg/d for 2 d or 10 mg/kg/d for 3 d. Mean fever clearance times were the same in the 2 treatment groups (97 h). There were 7 treatment failures, one in the 2 d group and 6 in the 3 d group (P = 0.07). Three of the 5 patients infected with nalidixic acid resistant strains of S. typhi had treatment failures, compared with 4 of 90 with nalidixic acid sensitive isolates (P < 0.0001; relative risk 13.5, 95% confidence interval 4.1-43%). Treatment with ofloxacin for 2 or 3 d is equally effective in adults with uncomplicated enteric fever caused by nalidixic acid sensitive strains of S. typhi. The epidemiology and management of nalidixic acid resistent typhoid needs further investigation.
Adult↗
Community-acquired septicaemia in southern Viet Nam: the importance of multidrug-resistant Salmonella typhi.
In a prospective study conducted between mid 1993 and 1994, 437 adults and children were admitted with community-acquired septicaemia to an infectious diseases hospital in southern Viet Nam. Gram-negative aerobes accounted for 90% of isolates and were predominantly Salmonella typhi (67%), Sal. para-typhi A (3%), Escherichia coli (10%), and Klebsiella spp. (5%). Other Salmonella spp. (1%), Pseudomonas aeruginosa (1%), Neisseria meningitidis (0.5%) and Haemophilus influenzae (0.2%) were uncommon. Staphylococcus aureus (5.5%) and Streptococcus pneumoniae (2%) were the most common Gram-positive isolates. Patients with enteric fever were younger (median age 16 years, range 1-63) than the other patients (median age 43 years, range 1-88) (P < 0.001) and had a lower mortality rate (0.3% vs. 23%; relative risk 69.5, 95% confidence interval 9.5-507.8; P < 0.0001). Over 70% of the Sal. typhi isolated were multi-drug-resistant, and 4% were resistant to nalidixic acid. Multidrug-resistant Sal. typhi is a major cause of community-acquired septicaemia in Viet Nam.
Adolescent↗
Effects of xenogeneic thymic transplantation in baboons.
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Animals↗