The efficacy and tolerability of antibiotics in scrub typhus: an updated network meta-analysis of randomized controlled trials.

OBJECTIVES: Inadequate treatment of scrub typhus results in severe complications such as septic shock and is also associated with a high median mortality rate of 6%. However, there has been no conclusive evidence about the superiority of different antibiotics in managing scrub typhus in terms of efficacy and tolerability. METHODS: We conducted a network meta-analysis (NMA) using the frequentist method. The included participants were pediatric and adult patients infected with scrub typhus. The primary outcome was the cure rate in the patients included. The subgroup analysis was done according to pediatric or adult patients. RESULTS: Overall, 14 randomized controlled trials (RCTs) with 1264 participants were included in this study. The NMA revealed that all the investigated antibiotics were associated with cure rates similar to those of doxycycline. The chloramphenicol and minocycline were ranked to be associated with the highest cure rate in the pediatric subgroup and adult subgroup, respectively. Second-generation quinolones, including ofloxacin, ciprofloxacin, and chloramphenicol, were associated with significantly lower adverse event rates than doxycycline. CONCLUSION: The current updated NMA provides evidence for the efficacy of chloramphenicol and minocycline in scrub typhus management. However, future large-scale RCTs with longer follow-up times are warranted.

[Role of chloramphenicol in current clinical practice].

INTRODUCTION: Chloramphenicol is an antibiotic with a broad spectrum of action and excellent tissue penetration. It had been widely used in clinical practice until the 1970s, but due to its potential myelotoxicity, it was gradually replaced by newly introduced antibiotics in the following years. The aim of the study was to find out to what extent and with what experience it is currently used in the Czech Republic. METHODS: A questionnaire survey was conducted in July and August 2022. The heads of all inpatient infectious diseases departments, hospital infectious diseases specialists and consulting microbiologists from antibiotic centers in large teaching hospitals without an infectious diseases department were asked to fill out the questionnaire. RESULTS: Thirty-five out of 39 hospitals contacted took part in the study, a response rate of 90 %. Chloramphenicol is used in 37 % of participating hospitals, with a frequency of up to 10 patients treated per year. The most common indications are brain abscesses, purulent meningitis, intra-abdominal, pelvic and lung abscesses, and polymicrobial infections with anaerobes. Chloramphenicol is almost always administered as an alternative antibiotic because of polyvalent allergy, bacterial resistance, and failure of previous treatment. Sixty-six percent of respondents described the effect as reliable or partially reliable, 34 % did not rate the effect. Fifty-two percent of respondents considered a dose of 8-9 g to be the maximum dose for an adult patient. In practice, 60 % of respondents did not encounter or could not assess the myelotoxic effects of chloramphenicol, 37 % observed reversible bone marrow suppression at least once, and only one respondent encountered aplastic anemia once. CONCLUSION: Unfortunately, chloramphenicol is currently used in less than half of hospitals in the Czech Republic. Because of its unique properties, it still has a place in today's anti-infective treatment. When properly indicated and after weighing the benefits and risks, it can be a suitable and sometimes life-saving alternative.

A worldwide systematic review and meta-analysis of bacteria related to antibiotic-associated diarrhea in hospitalized patients.

INTRODUCTION: Antibiotic-associated diarrhea (AAD) is a major hospital problem and a common adverse effect of antibiotic treatment. The aim of this study was to investigate the prevalence of the most important bacteria that cause AAD in hospitalized patients. MATERIALS AND METHODS: PubMed, Web of Science and Scopus databases were searched using multiple relevant keywords and screening carried out based on inclusion/exclusion criteria from March 2001 to October 2021. The random-effects model was used to conduct the meta-analysis. RESULTS: Of the 7,377 identified articles, 56 met the inclusion criteria. Pooling all studies, the prevalence of Clostridioides (Clostridium) difficile, Clostridium perfringens, Klebsiella oxytoca, and Staphylococcus aureus as AAD-related bacteria among hospitalized patients were 19.6%, 14.9%, 27%, and 5.2%, respectively. The prevalence of all four bacteria was higher in Europe compared to other continents. The highest resistance of C. difficile was estimated to ciprofloxacin and the lowest resistances were reported to chloramphenicol, vancomycin, and metronidazole. There was no or little data on antibiotic resistance of other bacteria. CONCLUSIONS: The results of this study emphasize the need for a surveillance program, as well as timely public and hospital health measures in order to control and treat AAD infections.

Evaluation of the Acute Effects and Oxidative Stress Responses of Phenicol Antibiotics and Suspended Particles in Daphnia magna.

Suspended particles (SP) exist widely in various water systems and are able to adsorb other pollutants in water, producing ecotoxic effects on aquatic nontarget species. Until now, however, few studies have focused on the effects of SP on antibiotics. Therefore, the present study investigated the effects of the mixtures of SP and phenicol antibiotics (chloramphenicol [CAP], thiamphenicol [TAP]) on acute toxicity and oxidative stress responses in Daphnia magna. The results indicated that the acute toxicity of phenicol antibiotics in D. magna was increased when combined with SP. Besides, the immobilization of daphnids caused by phenicol drugs in the presence of 10 mg/L of SP was more intense than that with 200 mg/L of SP. Furthermore, the impact of SP with diverse concentrations on the activity of catalase and the level of reduced glutathione in D. magna was different. Notably, almost all CAP + TAP + SP treatments markedly increased malondialdehyde content in D. magna, causing potential cellular oxidative damage in D. magna. In summary, the present study provides insights into the toxic effects of phenicol antibiotic and SP mixtures on aquatic organisms. Environ Toxicol Chem 2021;40:2463-2473. © 2021 SETAC.

Louse-borne relapsing fever-A systematic review and analysis of the literature: Part 2-Mortality, Jarisch-Herxheimer reaction, impact on pregnancy.

Louse-borne relapsing fever (LBRF) is a classical epidemic disease, which in the past was associated with war, famine, poverty, forced migration, and crowding under poor hygienic conditions around the world. The disease's causative pathogen, the spirochete bacterium Borrelia recurrentis, is confined to humans and transmitted by a single vector, the human body louse Pediculus humanus corporis. Since the disease was at its peak before the days of modern medicine, many of its aspects have never been formally studied and to date remain incompletely understood. In order to shed light on some of these aspects, we have systematically reviewed the accessible literature on LBRF since the recognition of its mode of transmission in 1907, and summarized the existing data on mortality, Jarisch-Herxheimer reaction (JHR), and impact on pregnancy. Publications were identified by using a predefined search strategy of electronic databases and a subsequent review of the reference lists of the obtained publications. All publications reporting patients with a confirmed diagnosis of LBRF published in English, French, German, and Spanish since 1907 were included. Data extraction followed a predefined protocol and included a grading system to judge the certainty of the diagnosis of reported cases. The high mortality rates often found in literature are confined to extreme scenarios. The case fatality rate (CFR) of untreated cases is on average significantly lower than frequently assumed. In recent years, a rise in the overall CFRs is documented, for which reasons remain unknown. Lacking standardized criteria, a clear diagnostic threshold defining antibiotic treatment-induced JHR does not exist. This explains the wide range of occurrence rates found in literature. Pre-antibiotic era data suggest the existence of a JHR-like reaction also in cases treated with arsenicals and even in untreated cases. LBRF-related adverse outcomes are observed in 3 out of 4 pregnancies.

Unsafe "crossover-use" of chloramphenicol in Uganda: importance of a One Health approach in antimicrobial resistance policy and regulatory action.

Since the introduction of antibiotics into mainstream health care, resistance to these drugs has become a widespread issue that continues to increase worldwide. Policy decisions to mitigate the development of antimicrobial resistance are hampered by the current lack of surveillance data on antibiotic product availability and use in low-income countries. This study collected data on the antibiotics stocked in human (42) and veterinary (21) drug shops in five sub-counties in Luwero district of Uganda. Focus group discussions with drug shop vendors were also employed to explore antibiotic use practices in the community. Focus group participants reported that farmers used human-intended antibiotics for their livestock, and community members obtain animal-intended antibiotics for their own personal human use. Specifically, chloramphenicol products licensed for human use were being administered to Ugandan poultry. Human consumption of chloramphenicol residues through local animal products represents a serious public health concern. By limiting the health sector scope of antimicrobial resistance research to either human or animal antibiotic use, results can falsely inform policy and intervention strategies. Therefore, a One Health approach is required to understand the wider impact of community antibiotic use and improve overall effectiveness of intervention policy and regulatory action.

Breve historia del cloranfenicol en oftalmología. ¿Es seguro su uso? / Brief history of chloramphenicol in ophthalmology. Is it safe to use?

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Identification of chloramphenicol in human hair leading to a diagnosis of factitious disorder.

Introduction: Chloramphenicol (2,2-dichloro-N-[1,3-dihydroxy-1-(4-nitrophenyl)porpan-2-yl]acetamide) is a bacteriostatic antibiotic of the phenicolated family, used in the past to treat meningitis, plague, cholera, or typhoid fever. Treatment with chloramphenicol can have life threatening side effects, the most serious of which is aplastic anemia, which may be fatal. For this reason, the antibiotic was removed from the French market in 2008.Case report: In this paper, the authors report the case of a woman consuming chloramphenicol possibly in the context of factitious disorder. After a capsule containing chloramphenicol was discovered in her hospital bed, a hair specimen (about 16 cm, brown, not oriented) was collected and sent to the toxicological laboratory in order to document exposure to chloramphenicol.Results: The drug was identified in the hair specimen of the subject at 13.7 ng/mg.Discussion: Identification of chloramphenicol in hair has not been reported in the literature. As consequence, the interpretation of the concentration, the dosage and the frequency of abuse are difficult to establish.Conclusion: Given the context, physicians considered the case as a possible factitious disorder, thus being a unique observation of using chloramphenicol in such a context.

Ultrasound assisted dispersive liquid-liquid microextraction for fast and accurate analysis of chloramphenicol in honey.

Honey is a food produced from honey bee widely used for the sweetening power and for its biological properties. In order to prevent the infection of the hive, different xenobiotics (antibiotics, pesticide) were frequently employed. One of these substances is the chloramphenicol, that given its chemical stability could often found in food. Chloramphenicol have several side effects in humans after their ingestion and for this reason their intake must be avoid. The aim of this study, was developed an ultrasound-assisted dispersive liquid-liquid microextraction method coupled with UHPLC MS/MS determination, for fast and accurate analysis of chloramphenicol in honey. The parameters affecting on extraction efficiency were carefully optimized using an experimental design in order to maximized the recovery reducing matrix effects. After the optimization the method was validated and successfully applied to 66 honey samples.

Characterization of antimicrobial resistance markers & their stability in Salmonella enterica serovar Typhi.

BACKGROUND & OBJECTIVES: Typhoid fever is a major cause of morbidity and mortality in the developing countries including India. Resistance to multiple antimicrobial agents is an emerging global problem that has serious impact on the treatment of disease. There are many factors associated with the emergence of resistance. Most important of them is the acquisition and further transmission and spread of resistance markers among various bacterial species. Therefore, we conducted this study to characterize the resistance plasmids in terms of their transferability and stability among Salmonella enterica serovar Typhi. METHODS: Six multidrug-resistant S. Typhi isolates were evaluated for the stability and transfer of resistance markers. The resistance plasmids were also checked for the presence of RepHI1A replicon. RESULTS: All resistance markers were found to be transferred to the recipient through conjugation and transformation, except for nalidixic acid. None of the resistance plasmid was found to harbour RepHI1A replicon and therefore, did not belong to incompatibility group IncHI1. Resistance markers were found to be highly stable in all the isolates during serial passages and storage as stab cultures at different temperatures for different time periods. INTERPRETATION & CONCLUSIONS: Resistance markers for chloramphenicol, ampicillin, streptomycin and trimethoprim were transferred through conjugation as well as transformation whereas that for nalidixic acid was not transferred in any of the isolates. Markers for chloramphenicol and streptomycin resistance were found to be most stable during various storage conditions. Presence of small-sized non-IncHI1 resistance plasmids is a matter of concern due to their capability to exist inside the host, thereby increasing the possibility of their transmission and spread among S. Typhi and other bacterial species.

Lactic Acidosis with Chloramphenicol Treatment in a Child with Cystic Fibrosis.

Children with cystic fibrosis are commonly colonized with multi-resistant bacteria. In such patients, infectious exacerbation may require salvage therapy with uncommonly used antimicrobials, including chloramphenicol. Chloramphenicol is rarely used nowadays because of the associated severe adverse events. We describe the case of a 15-year-old female with terminal cystic fibrosis who required intravenous (IV) chloramphenicol treatment for a Burkholderia cepacia (B. cepacia) exacerbation. The child subsequently developed lactic acidosis and secondary respiratory compensation adding to her baseline respiratory distress. Based on the Naranjo scale, the probability of chloramphenicol being the cause of the hyperlactatemia and associated respiratory distress was rated as probable, as the adverse effects resolved upon discontinuation of the drug. Subsequent genotyping for mitochondrial polymorphism (G3010A) confirmed a possible susceptibility to lactic acidosis from mitochondrial RNA-inhibiting agents such as chloramphenicol. Hyperlactatemia is a rare but life threatening adverse effect that has been previously reported with chloramphenicol exposure, but is not generally thought of. Clinicians should be aware of this potentially life threatening, but reversible adverse event. Lactate should be monitored under chloramphenicol and it should be discontinued as soon as this complication is suspected, especially in patients with low respiratory reserve.

Novel Hybrid Peptide Cecropin A (1-8)-LL37 (17-30) with Potential Antibacterial Activity.

Hybridizing different antimicrobial peptides (AMPs) is a particularly successful approach to obtain novel AMPs with increased antimicrobial activity but minimized cytotoxicity. The hybrid peptide cecropin A (1-8)-LL37 (17-30) (C-L) combining the hydrophobic N-terminal fragment of cecropin A (C) with the core antimicrobial fragment of LL37 (L) was designed and synthesized. C-L showed higher antibacterial activity against all indicator strains than C and L, and no hemolytic activity to sheep erythrocytes was observed. C-L kills bacterial cells and causes disruption of surface structure, as determined by scanning electron microscopy. Synergistic effects were observed in the combination of C-L with several antibiotics (chloramphenicol, thiamphenicol, or neomycin sulfate) against Escherichia coli and Staphylococcus aureus.

Periconceptional and Gestational Exposure to Antibiotics and Childhood Asthma.

BACKGROUND: Previous studies suggest that maternal antibiotics exposure during pregnancy may increase the risk of childhood asthma, but the results were inconsistent. Furthermore, most studies did not examine periconception period as an exposure window. We aim to assess the associations between maternal exposure to specific antibiotics before and during pregnancy and the risk of asthma in early childhood. METHODS: Data from the Collaborative Perinatal Project were used. Maternal exposure to antibiotics before and during pregnancy was recorded at each prenatal visit. A total of 39,907 singleton children were followed up to 7 years of age. Multilevel multiple logistic regression models were used to control for potential confounders and account for multiple pregnancies per woman. RESULTS: Maternal use of penicillin or chloramphenicol was associated with an increased risk of asthma in the offspring (adjusted odds ratio = 1.21, 95% confidence interval 1.08-1.36 for penicillin; 1.72 [1.14-2.59] for chloramphenicol). The risk was significantly increased if penicillin or chloramphenicol was used in the 1st trimester (1.09 [1.04-1.13] for penicillin and 1.23 [1.01-1.51] for chloramphenicol). CONCLUSION: Maternal exposure to certain antibiotics is associated with childhood asthma by 7 years of age. Early pregnancy may be a sensitive window.

Randomized Controlled Trial of Azithromycin versus Doxycycline or Chloramphenicol for Treatment of Uncomplicated Pediatric Scrub Typhus.

OBJECTIVE: To evaluate the efficacy and safety of azithromycinfor treatment of uncomplicated pediatric scrub typhus. MATERIAL AND METHOD: A randomized controlled trial was performed. We compared azithromycin with doxycycline or chloramphenicol in uncomplicated pediatric scrub typhus from inpatient pediatric department of Chiangrai Prachanukroh Hospital. The primary outcome was cure rate at day 3. The secondary outcomes were timing to defervescence within 72 hours, side effects, and relapsed rate. We compared data between both groups with Fisher's exact test or Mann-Whitney U test, and failure rate was demonstrated by Kaplan-Meier survival curve and Log-rank test. RESULTS: We included 57 patients, ofwhom, 28 were assigned to doxycycline or chloramphenicol (control group) and 29 to azithromycin (study group). The baseline characteristics of both groups were similar The cure rate was 85.7% in the doxycycline or chloramphenicol group, as compared to 79.3% in the azithromycin group (p = 0.73), and a median time to defervescence was 30 hours (IQR 21, 48) vs. 36 hours (IQR 20, 68) respectively (p = 0.166). There was a little minor side effect in azithromycin group. No relapsed was found in either groups. CONCLUSION: Azithromycin was as effective as doxycycline or chloramphenicol in treatment of uncomplicated pediatric scrub typhus.

Exposure to topical chloramphenicol during pregnancy and the risk of congenital malformations: a Danish nationwide cohort study.

PURPOSE: To investigate whether exposure to topical chloramphenicol in the first trimester of pregnancy is associated with congenital malformations. METHODS: The authors conducted a nationwide cohort study including all women giving live birth between 1997 and 2011 in Denmark. All women redeeming at least one prescription of chloramphenicol eye drops or eye ointment during the first 84 days of pregnancy were identified. Logistic regression was used to estimate the odds ratios of malformations among exposed women compared to non-exposed women. RESULTS: 966 372 births between 1997 and 2011 were included. A total of 6024 women were exposed to topical chloramphenicol in the first trimester. The rate of congenital malformations was 3.50% among offspring of exposed mothers and 3.49% among unexposed. Exposure to topical chloramphenicol in the first trimester was not associated with major congenital malformations (adjusted odds ratio = 1.06, 95% CI 0.91-1.22) or specific major malformations. The number of redeemed prescriptions decreased significantly during pregnancy as compared to before and after pregnancy (p < 0.0001). CONCLUSION: In this study, we found no association between dispensing of chloramphenicol eye drops or eye ointment in the first trimester of pregnancy and major congenital malformations. This is in accordance with a previous study analysing the risk of systemic chloramphenicol.