Study on the efficacy of ceftriaxone versus azithromycin for the treatment of uncomplicated enteric fever among the patients admitted in a tertiary level hospital

Background: Typhoid fever is a severe debilitating and potentially life threating illness. In Bangladesh, typhoid fever is a round the year problem which sometimes take epidemic proportions. The reasons behind such occurrences are unsafe water supply, defective sewage system and unhygienic food handling practice. This study aimed to compare the efficacy of ceftriaxone and azithromycin in the treatment of uncomplicated enteric fever.Methods: An observational study was conducted at the department of pharmacology in Dhaka medical college, Dhaka, Bangladesh. Data were collected from blood culture positive patients for Salmonella typhi and Salmonella paratyphi, who admitted in the Dhaka medical college and hospital, Dhaka during the period of July 2015 to June 2016. Data was collected by using a structured questioner, face to face interview, physical examination and investigation reports. Patients were hospitalized during the entire treatment period and at admission evaluation was made by history and physical examination in a structured format. Subjects ware asked regarding changes in symptoms and possible adverse effects of the study drugs. All patients were asked to return two weeks after completion of treatment for follow up. Blood culture of Salmonella typhi or Salmonella paratyphi were done in all cases. Total 91 patients were culture positive for either S. typhi or S. paratyphi which were finally studied.Results: During the study period out of 91 patients, 51 were receiving ceftriaxone and 40 were receiving azithromycin. Clinical cure was achieved in 46 patients (90%) of ceftriaxone group and in 31 patients (78%) in the azithromycin group. There were no significant differences of clinical cure between both treatment groups (p>0.05). Mean fever clearance time in ceftriaxone group was 3±1.4 days and was 4±1.6 days for azithromycin group. Difference in fever clearance time was statistically significant (p<0.05). No clinical relapses were detected in any study subject. No major side effects of both drugs occurred in any subject.Conclusions: These results indicated that both ceftriaxone and azithromycin were effective against enteric fever caused by sensitive organisms and multi drug resistant S. typhi and S. paratyphi. It is concluded that ceftriaxone is more effective and can be a convenient alternative for the treatment of enteric fever, especially in developing countries like us where medical resources are scarce.

The Use of Oseltamivir as Adjunctive Therapy for the Treatment of Hand-Food-and-Mouth Disease: A Meta-Analysis of Randomized Clinical Trials

Background: Hand-foot-and-mouth disease (HFMD) is a common childhood illness caused by enteroviruses. Oseltamivir (OS), a neuraminidase inhibitor, has been frequently used as an adjunctive therapy for the treatment of HFMD. Solid evidence, however, is lacking regarding the efficacy of such adjunctive therapy. This work is to conduct a meta-analysis of randomized clinical trials (RCTs) to assess the efficacy of oseltamivir for HFMD in children.Methods: Eligible studies from inception to October 10, 2020 were identified by searching six databases (PubMed, Embase, CENTRAL, CNKI, Wanfang, and VIP database). Quality of evidence was assessed using the Cochrane Collaboration tool.Results: Of a total of 91 entries, 11 RCTs involving 977 HFMD children were included in the final analysis. The results showed that the therapy combined with oseltamivir was more effective, with higher effective rate (RR, 0.84; 95% CI, 0.80 to 0.87; p &lt; 0.01), shorter fever clearance time (days) (SMD, −0.74; 95% CI, −1.12 to −0.35; p &lt; 0.01), shorter rash regression time (days) (MD, −0.89; 95% CI, −1.05 to −0.72; p &lt; 0.01) and shorter clinical cure time (SMD, −1.08; 95% CI, −1.55 to −0.61; p &lt; 0.01). No significant difference was observed in the risk of adverse reactions between the groups with and without oseltamivir.Conclusion: The use of oseltamivir as adjunctive therapy shows effectiveness and no increased risk of adverse reactions for the treatment of HFMD in children.

Clinical profile and predictors of severity in paediatric scrub typhus with pulmonary involvement

Pulmonary involvement is common in children with scrub typhus. Our paper outlines the clinical characteristics of pulmonary involvement and analyses the predictors of its severity. All scrub typhus serology-positive (optical density >0.5) children with pulmonary symptoms were included. Of 506 serology-positive scrub typhus cases, 256 (50.5%) had pulmonary symptoms, of whom 50 (9.8%) were severe. These severe cases were compared with non-severe cases. Interstitial pneumonitis was the commonest chest radiographic finding. Logistic regression analysis identified ‘fever clearance time’ >48 h, facial puffiness, maculopapular rash and anaemia to be significantly associated with severe pulmonary involvement.

Trimethoprim-sulfamethoxazole Versus Azithromycin for the Treatment of Undifferentiated Febrile Illness in Nepal: A Double-blind, Randomized, Placebo-controlled Trial

Background Azithromycin and trimethoprim-sulfamethoxazole (SXT) are widely used to treat undifferentiated febrile illness (UFI). We hypothesized that azithromycin is superior to SXT for UFI treatment, but the drugs are noninferior to each other for culture-confirmed enteric fever treatment. Methods We conducted a double-blind, randomized, placebo-controlled trial of azithromycin (20 mg/kg/day) or SXT (trimethoprim 10 mg/kg/day plus sulfamethoxazole 50 mg/kg/day) orally for 7 days for UFI treatment in Nepal. We enrolled patients &gt;2 years and &lt;65 years of age presenting to 2 Kathmandu hospitals with temperature ≥38.0°C for ≥4 days without localizing signs. The primary endpoint was fever clearance time (FCT); secondary endpoints were treatment failure and adverse events. Results From June 2016 to May 2019, we randomized 326 participants (163 in each arm); 87 (26.7%) had blood culture–confirmed enteric fever. In all participants, the median FCT was 2.7 days (95% confidence interval [CI], 2.6–3.3 days) in the SXT arm and 2.1 days (95% CI, 1.6–3.2 days) in the azithromycin arm (hazard ratio [HR], 1.25 [95% CI, .99–1.58]; P = .059). The HR of treatment failures by 28 days between azithromycin and SXT was 0.62 (95% CI, .37–1.05; P = .073). Planned subgroup analysis showed that azithromycin resulted in faster FCT in those with sterile blood cultures and fewer relapses in culture-confirmed enteric fever. Nausea, vomiting, constipation, and headache were more common in the SXT arm. Conclusions Despite similar FCT and treatment failure in the 2 arms, significantly fewer complications and relapses make azithromycin a better choice for empirical treatment of UFI in Nepal. Clinical Trials Registration NCT02773407.

Surveillance of the efficacy of artemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum among children under five years in Est Mono district, Togo, 2017

Background Malaria is a major public health problem in Togo. Guangzhou University of Chinese medicine of China, and the Ministry of Health and Social Security of Togo launched a nationwide artemisinin compound Mass Drug Administration Project in East Mono with a population of 150,000. Before launching the project, the sensitivity test of artemisinin piperaquine tablet was conducted in Elawagnon general clinic. On this background, we evaluated the efficacy and safety of artemisinin piperaquine in the treatment of uncomplicated falciparum malaria in children under five years of age. Methods In this study, children aged 6-59 months without complications of falciparum malaria were observed, and the selected cases were treated with artemisinin piperaquine. The patients were followed up for 28 days to observe the fever clearance time, parasitemia, gametophyte, cure rate, haemoglobin and msp-2 gene polymorphism. The primary end point was the 28-day cure rate, and PCR corrected reinfection and recrudescence. This research was conducted according to standardized WHO protocol for the assessment of the efficacy of anti-malarial treatment. Results A total of 91 children participated in the study. The adequate clinical and parasitological response (ACPR) before PCR-corrected were 66 (72.52%) and 90 (98.90%) after PCR-corrected. The patient was well tolerated to artemisinin piperaquine and no serious adverse reactions were observed. The average hemoglobin level increased by 0.05g/dl per day (p< 0.0001). The gametophyte doesn’t declined at the beginning of treatment, however, 14 days later, it dropped(D21:p<0. 05; D28: p< 0. 01). In the msp-2 gene polymorphism study of 24 children with positive parasite after treatment, 1 case of msp-2 with 3D7 haplotype and FC27 haplotype was reported, indicating that it’s recrudescence, with a frequency of 4.2% (1/24); The others maybe reinfection, with a frequency of 95.8% (23/24). Conclusion Artemisinin piperaquine was effective in treating uncomplicated falciparum malaria in children under 5 years of age in Togo and well tolerated. Plasmodium falciparum in Togo remains sensitive to artemisinin piperaquine, which could be used as a trial drug in the region. Trial Registration Trial registration: ECGPHCM No. B2017-054-01; MHSST AVIS N° 0001/2016/CBRS du 07 janvier 2016. Registered 17 March 2014, http://www.chinadrugtrials.org.cn/eap/main

Evaluation of Arthemether-Lumefantrine Effectiveness in Malaria Treatment in Nnewi, Nigeria

As an acute and chronic mosquito-borne disease of man, malaria is characterized by chills and fever, anaemia, splenomegaly and damage to other vital organs such as liver and brain. With reportedly increasing incidence of its lethargy in sub-Sahara Africa, current study was thus designed to investigate the effectiveness of one of malaria’s management pharmacological variety, Arthemether-Lumefantrine amongst residents of Nnewi community of Anambra State, Nigeria. Hundred (100) human subjects from the General Outpatients Department (GOPD) of the Nnamdi Azikiwe University Teaching Hospital, Nnewi, who showed signs and symptoms of malaria, were recruited for the study. After gaining subjects’ consent and co-operation, Artemether-Lumefantrine combination (combination therapy) was then orally administered to the patients; with Blood samples collected 10 min before, and on days 4, 8, 10 and 14 after drug administration. Efficacy evaluation of parasitological cure rates was also determined after the 14th day. In addition to cure rate, fever clearance time (FCT), as the time from drug administration till axillary temperature fell below 37.5oC and remained so for at least 48 hours was also determined. In any case, obtained data were analysed using appropriate descriptive statistical (mean, standard deviation, frequency and percentage). The Chi square distribution test was performed to ascertain the goodness of fit of obtained variables. p-value was determined at 95% confidence interval, with significance level set at p < 0.05. Upon analysis, Study found after treatment at day 4, that cure rate for patients <16 years (paediatrics) was 52%, with those >16 years (adults) being 72%. On day 8 after treatment, cure rates for patients <16 years (paediatrics) was 89%, while that of those >16 years (adults) was 94%, while on day 10 and 14 the cure rate for patients <16 years became 98% while that of those >16 years was 100%.

Clinical Characteristics and Outcome of Children Hospitalized With Scrub Typhus in an Area of Endemicity

Background Scrub typhus, caused by Orientia tsutsugamushi, is a major cause of acute febrile illness in children in the rural tropics. Methods We recruited 60 febrile pediatric patients with a positive scrub typhus rapid diagnostic test result and 40 healthy controls from Chiang Rai Province in northern Thailand. Diagnosis was confirmed by the detection of (1) O. tsutsugamushi–specific DNA in blood or eschar samples with a polymerase chain reaction assay, (2) a fourfold rise in immunoglobulin M (IgM) titer to ≥1:3200 in paired plasma samples with an indirect immunofluorescence assay (IFA), or (3) a single IgM titer of ≥1:3200 in an acute plasma sample with an IFA. Demographic, clinical, and laboratory data were collected, and patients were followed up for 1 year. Results Diagnosis was confirmed in 35 (58%) of 60 patients, and all controls tested negative for scrub typhus. Patients with confirmed scrub typhus had clinical symptoms, including fever (35 of 35 [100%]), eschar (21 of 35 [60%]), cough (21 of 35 [60%]), tachypnea (16 of 35 [46%]), lymphadenopathy (15 of 35 [43%]), and headache (14 of 35 [40%]). Only 4 (11%) of 35 patients received appropriate antibiotic treatment for scrub typhus before admission. The median fever-clearance time was 36 hours (interquartile range, 24–53 hours). Complications observed include hepatitis (9 of 35 [26%]), severe thrombocytopenia (7 of 35 [20%]), pneumonitis (5 of 35 [14%]), circulatory shock (4 of 35 [11%]), and acute respiratory distress syndrome (3 of 35 [9%]). Treatment failure, defined by failure to defervesce within 72 hours of antibiotic treatment initiation, was noted in 8 (23%) of 35 patients, and 1 (3%) of the 35 patients died. No evidence of relapse or reinfection was found. Conclusion Pediatric scrub typhus in northern Thailand is often severe and potentially fatal with delays in treatment a likely contributing factor. Additional studies to investigate the bacterial, pharmacologic, and immunologic factors related to treatment outcome along with measures to improve public awareness should be prioritized.

The Effectiveness of Different Doses of Intravenous Immunoglobulin on Severe Hand, Foot and Mouth Disease: A Meta-Analysis

Objective: To conduct a meta-analysis of evidence from randomized controlled trails (RCTs) of different doses of intravenous immunoglobulin (IVIG) in children with severe hand, foot and mouth disease (HFMD) to provide the scientific basis for clinical practice. Methods: A search of PubMed-Medline, CNKI, Wanfang, and VIP database (until June 30, 2017) was performed and Software RevMan5.3 was used to evaluate the effect of different doses of IVIG on HFMD in RCTs. We used random-effects models (or fixed-effects models) and generic inverse variance methods to process quantitative data, followed by a leave-one-out method for sensitivity analysis. Results: From a total of 420 entries identified via searches, 8 RCTs involving 1,450 patients were included in the final analysis. The results of the meta-analysis showed that compared with conventional therapy alone, conventional therapy combined with IVIG had shorter fever clearance time, shorter rash regression time, and shorter clinical cure time. Subgroup analyses showed that the high-dose group (1 g/kg/day) had shorter fever clearance time (p < 0.05), shorter rash regression (p< 0.05), shorter remission time of neurological symptoms (p < 0.05), but longer clinical cure time (p > 0.05). Conclusion: The high-dose group has a better prognosis; however, the advantages and disadvantages should be carefully considered when deciding the doses in the treatment of severe HFMD.

Evaluation of Efficacy and Safety of Artemisinin Derivatives for Treatment of Severe Malaria: A Meta-Analysis Approach

Despite progress in antimalarial management and intensive care, the prevalence of malaria is growing and the mortality rate is very high. Yet even with timely treatment of quinine in maximum doses, the death in patients of severe malaria is very high. The successive synthesis of artemether and artesunate has supplied highly successful substitutes to quinine. This systematic review and meta-analysis approach provides a comparative outcome analysis of Artemisinin derivatives (intervention) and other antimalarials (comparison) in the paediatric and adult population. From the year 1985 to the year 2015, studies were recognized using database searches, citation searches of selected articles. The electronic databases searched engines: Pubmed, Web of Science, Global Health, Medline and Cochrane review of Journals up to April 2015. We selected published randomized controlled clinical trials information comparing artemisinin derivatives and quinine for the management of severe malaria in adult and paediatric population as per WHO malaria treatment guideline, any gender, age group less than or greater than 15 years who were diagnosed with severe malaria. The primary outcome was efficacy in terms of parasite clearance time (PCT), Parasite clearance at D7 and D28 and fever clearance time (FCT). The secondary outcome was the mortality and adverse events. We measured 95% confidence interval by the using of REVMAN software version 5.3 for meta-analysis and summarized the collected data on the basis of characteristics of inclusion criteria of articles. We included total 33 RCTs, enrolling 8396 paediatric and adult patients who were suffering from severe malaria. Artemisinin and its derivatives showed mean parasite clearance time (PCT) (MD -8.50 hours, 95% CI -9.41 to -7.60) and mean fever clearance time (FCT) (MD -9.51 hours, 95% CI -11.22 to -7.81) P less than 0.00001 statistically significant as compared to quinine therapy. Artemisinin and its derivatives showed a statistically significant clearance of parasites when compared to quinine at Day 7 (OR 0.41, 95% CI 0.21, 0.81, random effect model, P=0.01). Overall artemisinin derivatives has shown more parasite clearance at D28 than quinine group (Odds ratio 0.54, 95% CI 0.23, 1.29, random effect model, P=0.17). We evaluated secondary outcomes mortality which showed artemisinin or its derivatives a statistically significant mortality reduction as compared to quinine. (Odds Ratio 0.77, 95% CI 0.67 to 0.89; 27 trials, 8396 participants) P=0.0002 and also showed a statistically significant reduction in the adverse events as compared with quinine (RR0.73, 95% CI 0.62 to 0.87) P=0.003. An overall positive result was found with artemisinin derivatives across all evaluated outcomes.

A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus

Background Murine typhus, or infection with Rickettsia typhi, is a global but neglected disease without randomized clinical trials to guide antibiotic therapy. Methods A prospective, open, randomized trial was conducted in nonpregnant, consenting inpatient adults with rapid diagnostic test evidence of uncomplicated murine typhus at 2 hospitals in Vientiane, Laos. Patients were randomized to 7 days (D7) or 3 days (D3) of oral doxycycline or 3 days of oral azithromycin (A3). Primary outcome measures were fever clearance time and frequencies of treatment failure and relapse. Results Between 2004 and 2009, the study enrolled 216 patients (72 per arm); 158 (73.2%) had serology/polymerase chain reaction (PCR)–confirmed murine typhus, and 52 (24.1%) were R. typhi PCR positive. The risk of treatment failure was greater for regimen A3 (22.5%; 16 of 71 patients) than for D3 (4.2%; 3 of 71) or D7 (1.4%; 1 of 71) (P &lt; .001). Among R. typhi PCR–positive patients, the area under the time-temperature curve and the fever clearance time were significantly higher for A3 than for D3 (1.8- and 1.9-fold higher, respectively; P = .005) and D7 (1.5- and 1.6-fold higher; P = .02). No patients returned with PCR-confirmed R. typhi relapse. Conclusion In Lao adults, azithromycin is inferior to doxycycline as oral therapy for uncomplicated murine typhus. For doxycycline, 3- and 7-day regimens have similar efficacy. Azithromycin use in murine typhus should be reconsidered. Investigation of genomic and phenotypic markers of R. typhi azithromycin resistance is needed. Clinical Trial Registration ISRCTN47812566.