How Clavulanic Acid Inhibits Serine ß-Lactamases.

Clavulanic acid is a medicinally important inhibitor of serine ß-lactamases (SBLs). We report studies on the mechanisms by which clavulanic acid inhibits representative Ambler class A (TEM-116), C (Escherichia coli AmpC), and D (OXA-10) SBLs using denaturing and non-denaturing mass spectrometry (MS). Similarly to observations with penam sulfones, most of the results support a mechanism involving acyl enzyme complex formation, followed by oxazolidine ring opening without efficient subsequent scaffold fragmentation (at pH 7.5). This observation contrasts with previous MS studies, which identified clavulanic acid scaffold fragmented species as the predominant SBL bound products. In all the SBLs studied here, fragmentation was promoted by acidic conditions, which are commonly used in LC­MS analyses. Slow fragmentation was, however, observed under neutral conditions with TEM-116 on prolonged reaction with clavulanic acid. Although our results imply clavulanic acid scaffold fragmentation is likely not crucial for SBL inhibition in vivo, development of inhibitors that fragment to give stable covalent complexes is of interest.

Raoultella ornithinolytica Urinary Tract Infection in a Patient With Triple-Negative Breast Cancer.

Due to the challenges associated with accurately identifying Raoultella ornithinolytica as the causative agent in urinary tract infections (UTIs), coupled with limited guidance on treatment protocols, reports of similar cases still need to be made publicly available because of their increasing emergence. In this article, we present the first documented case of a UTI caused by Raoultella ornithinolytica in a patient with triple-negative breast cancer undergoing neoadjuvant chemotherapy. This case report highlights Raoultella ornithinolytica as an uncommon yet significant pathogen, particularly in immunocompromised patients. Given the bacterium's antibiotic resistance patterns, it emphasizes the importance of prompt, accurate identification methods and tailored treatment strategies, especially in vulnerable populations undergoing chemotherapy.

Patterns of Antibiotic Prescription in Endodontic Therapy in the Republic of Croatia.

In response to the global trend of decreasing antibiotic usage, this study aimed to evaluate the nature and frequency of antibiotic prescriptions in conjunction with endodontic therapy in Croatia and to assess the attitudes of Croatian dental practitioners towards the endodontic treatment of patients susceptible to bacterial endocarditis. A survey questionnaire was sent to all dental practitioners in Croatia, achieving a response rate of 27%. The most frequently prescribed antibiotic was penicillin with clavulanic acid (63.4%), while standalone penicillin was less prevalent (18.6%). For patients exhibiting penicillin allergies, 90% of respondents indicated clindamycin as their preferred alternative. Antibiotics were mostly prescribed for localized acute apical abscesses without fever, followed by prophylaxis for infectious endocarditis and cellulitis. Only 1.3% of the respondents reported frequent antibiotic prescriptions without accompanying local treatment. While a substantial proportion of surveyed practitioners professed familiarity with the latest guidelines for antibiotic prophylaxis, their choice of antibiotics did not consistently reflect this claim. Most respondents conducted endodontic procedures on patients at risk of bacterial endocarditis. The findings highlight a need for targeted continuing education for dental practitioners in the Republic of Croatia, ensuring their practices align with current guidelines and global trends in antibiotic prescription.

In Silico Study of the Potential of Brazilein Sappan Wood as a Beta-Lactamase Inhibitor against Extended-Spectrum Beta-Lactamase-Encoding Genes.

Background: Infectious illnesses are a serious health concern in Indonesia. Widespread use of self-medication by the community increases the risk of developing multi-drug resistant (MDR) bacteria. This study assessed the potential of sappan wood as an inhibitor of extended-spectrum beta-lactamase (ESBL) encoded by blaSHV, blaTEM and blaCTX-M genes. Method: In silico testing was conducted to develop an effective and economical starting strategy. Thereby, this study significantly advances the development of novel treatments to combat antibiotic resistance. Using clavulanic acid as the benchmark medicine, the potency of the beta-lactamase inhibitor brazilein was predicted. Using the Molegro Virtual Docker computer tool, docking was performed to estimate the chemical and physical properties of the compounds, as well as the biological activity of brazilein toward the required receptor. The receptors used were SHV-1 beta-lactamase, PDB code: 2H0T; TEM-1 beta-lactamase, PDB code: 4OQG and CTX-M-14 beta-lactamase, PDB code: 6VHS. Data analysis was performed by comparing the binding energies of the docking results between the ligands and the target receptor. The more stable the bond that formed between the ligand and the target receptor, the lower the bond energy. Results: The in silico test results on the blaSHV gene were as follows: binding energy of ligand MA4_400[A] = -100.699, brazilein = -82.206, clavulanic acid = -79.3704; in the blaTEM gene: ligand bond energy 2UL_301[B] = -107.681, brazilein = -82.0296, clavulanic acid = -103.3; in the blaCTX-M gene: X57_301[A] ligand bond energy = -86.6197, and brazilein = -88.1586, clavulanic acid = -101.933. Conclusion: The findings of this study demonstrate the significant potential of brazilein sappan wood to block the beta-lactamase activity of blaCTX-M.

Clavulanic Acid-Mediated Increases in Anterior Cingulate Glutamate Levels are Associated With Decreased Cocaine Craving and Brain Network Functional Connectivity Changes.

Background: There is an urgent need for pharmacological treatment for cocaine (COC) use disorder (CUD). Glutamatergic transmission in the prefrontal cortex is affected by addictive behaviors. Clavulanic acid (CLAV), a glutamate transporter GLT-1 (excitatory amino acid transporter) activator, is a clinical-stage medication that has potential for treating CUD. Methods: In a pilot study, nine participants with CUD received 500 mg CLAV with dose escalations to 750 mg and 1000 mg over 10 days. In 5 separate magnetic resonance imaging (MRI) sessions, brain anterior cingulate cortex (ACC) glutamate level and resting state network (RSN) functional connectivity (FC) were assessed using MR spectroscopy and functional MRI. Craving was assessed at the same time points, between baseline (before CLAV), 6 days, and 10 days of CLAV. Independent component analysis with dual regression was used to identify RSN FC changes from baseline to Days 6 and 10. Relationships among glutamate, craving, and resting state FC values were analyzed. Results: Participants who achieved high ACC glutamate levels after CLAV treatment had robust decreases in COC craving (r = -0.90, P = 0.0009, n = 9). The salience network (SN) and executive control network (ECN) demonstrated an association between increased FC after CLAV treatment and low baseline ACC Glu levels (SN CLAV 750 mg, r = -0.82, P = 0.007) (ECN CLAV 1000 mg, r = -0.667, P = 0.050; n = 9). Conclusions: Glutamate associated changes in craving and FC of the salience and executive control brain networks support CLAV as a potentially efficacious pharmacological treatment for CUD.

Clavulanic acid inhibits methamphetamine locomotor sensitization in mice and normalizes methamphetamine-induced changes in glutaminase mRNA levels in the nucleus accumbens.

Clavulanic acid (CLAV) is a component of Augmentin® that preserves antibiotic efficacy by inhibiting ß-lactamase activity. It also enhances cellular glutamate uptake and is a potential CNS therapeutic. Because increased glutamate transmission in brain reward circuits facilitates methamphetamine (METH) locomotor activation and sensitization, we tested the hypothesis that CLAV inhibits acute and sensitized locomotor responses to METH in mice and investigated effects of CLAV on METH-induced changes in glutaminase, the major glutamate-producing enzyme in the brain. Acute METH (3 mg/kg) produced hyperlocomotion that was reduced by CLAV (20 mg/kg but not 10 mg/kg). Mice injected with METH (3 mg/kg) every other day for 9 d and then challenged with METH 27 d later displayed locomotor sensitization. CLAV (10 mg/kg), when injected 15 min before each METH injection during the 9-d exposure interval, blocked locomotor sensitization induced by METH challenge. In METH-sensitized mice, mRNA levels of both isoforms of glutaminase (GLS and GLS2) were altered in the nucleus accumbens compared to mice exposed to a single injection of METH (i.e., GLS decreased and GLS2 increased). CLAV normalized the METH-induced GLS deficit but not the increase in GLS2. In summary, CLAV reduced acute and sensitized locomotor responses to METH and normalized the METH-induced reduction of GLS gene expression in the NAC. Given that glutaminases belong to the ß-lactamase superfamily and CLAV is a ß-lactamase inhibitor, our data point toward studying glutaminase as a therapeutic target of CLAV.

Exploring therapeutic options for mild diabetic-related foot infections: a comparative in vitro study of cefditoren versus amoxicillin/clavulanic acid.

Skin and soft tissue infections (SSTIs), and particularly diabetic-related foot infections (DFI), present diagnostic and therapeutic complexities, often leading to severe complications. This study aims to evaluate the in vitro efficacy of cefditoren and amoxicillin/clavulanic acid against typical DFI pathogens. Clinical samples from 40 patients with mild SSTIs were analyzed, revealing a predominance of Staphylococcus spp. and Streptococcus spp. species. Cefditoren exhibited activity against 90% of isolates, with superior potency over amoxicillin/clavulanic acid. These findings underscore the utility of cefditoren in empirical treatment of DFI, although a larger sample size would be desirable for further validation.

Favourable effect of clavulanic acid on the minimum inhibitory concentrations of cefixime and ceftibuten in ESBL-producing Escherichia coli and Klebsiella pneumoniae.

OBJECTIVES: The use of cephalosporins combined with clavulanate for the treatment of ESBL-harbouring Enterobacteriaceae has been scarcely described. We aimed to describe the effect of different concentrations of clavulanate in the MIC of cefixime and ceftibuten of ESBL-producing Escherichia coli and Klebsiella pneumoniae. METHODS: ESBL-producing E. coli and K. pneumoniae isolates were studied. Fixed concentrations of cefixime and ceftibuten (ranges of 32-0.25 and 64-0.5 ng/ml, respectively) were used. Combinations of cefixime/clavulanate and ceftibuten/clavulanate in different ratios (1:0, 1:1, 2:1, 4:1, 8:1, 16:1, 32:1) were tested. MIC were determined by broth microdilution. RESULTS: A total of 6 ESBL-producing E. coli, 6 ESBL-producing K. pneumoniae and 2 control E. coli were tested. When different quantities of clavulanate were added to cefixime and ceftibuten, greater than two-fold decreases in the MIC were observed. When testing the 1:1 cefixime/clavulanate ratio, 10/12 isolates were susceptible. When the ratios 2:1, 4:1, 8:1 and 16:1 were tested, susceptibility was noted for 9/12, 8/12, 4/12 and 5/12 isolates, respectively. Only 2/12 K. pneumoniae isolates were susceptible when the ratio 32:1 was tested. When testing ceftibuten/clavulanate, all isolates remained susceptible across all experiments. CONCLUSIONS: Clavulanic acid has a favourable effect in reducing the MIC of cefixime and ceftibuten in isolates of ESBL-producing E. coli and K. pneumoniae. Combining clavulanate with ceftibuten or cefixime could be a useful treatment strategy.

Effect of Soy Protein Products on Growth and Metabolism of Bacillus subtilis, Streptococcus lactis, and Streptomyces clavuligerus.

Microbial nitrogen sources are promising, and soy protein as a plant-based nitrogen source has absolute advantages in creating microbial culture medium in terms of renewability, eco-friendliness, and greater safety. Soy protein is rich in variety due to different extraction technologies and significantly different in the cell growth and metabolism of microorganisms as nitrogen source. Therefore, different soy proteins (soy meal powder, SMP; soy peptone, SP; soy protein concentrate, SPC; soy protein isolate, SPI; and soy protein hydrolysate, SPH) were used as nitrogen sources to culture Bacillus subtilis, Streptococcus lactis, and Streptomyces clavuligerus to evaluate the suitable soy nitrogen sources of the above strains. The results showed that B. subtilis had the highest bacteria density in SMP medium; S. lactis had the highest bacteria density in SPI medium; and S. clavuligerus had the highest PMV in SPI medium. Nattokinase activity was the highest in SP medium; the bacteriostatic effect of nisin was the best in SPI medium; and the clavulanic acid concentration was the highest in SMP medium. Based on analyzing the correlation between the nutritional composition and growth metabolism of the strains, the results indicated that the protein content and amino acid composition were the key factors influencing the cell growth and metabolism of the strains. These findings present a new, high-value application opportunity for soybean protein.

[Antibacterial therapy for acute streptococcal tonsillopharyngitis: results of a randomized comparative clinical trial with amoxicillin + clavulanic acid EXPRESS].

BACKGROUND: Acute tonsillopharyngitis is one of the most common types of respiratory tract infections. In case of bacterial etiologies of the disease, penicillin antibiotics are prescribed, in particular amoxicillin + clavulanic acid. Dispersible forms of antibiotics have a number of advantages over film-coated tablets and are characterized by better pharmacokinetic parameters that increase the effectiveness and safety of treatment, as well as patient compliance. AIM: To compare the effectiveness and safety of Amoxicillin + Clavulanic acid EXPRESS in the form of dispersible tablets and amoxicillin with clavulanic acid in film-coated tablets in the treatment of acute streptococcal tonsillopharyngitis. MATERIALS AND METHODS: A randomized comparative clinical study involved 60 adult patients diagnosed with acute streptococcal tonsillopharyngitis. Group 1 (n=30) received the Amoxicillin + Clavulanic acid EXPRESS, dispersible tablets, 875+125 mg 2 times a day at the beginning of meals. Group 2 (n=30) received Amoxiclav, film-coated tablets, 875+125 mg 2 times a day at the beginning of meals. The duration of the treatment was 10 days. The following procedures were performed to all participants: general clinical and otorhinolaryngological examinations, an express test to detect group A streptococcal antigens in a smear from the posterior pharyngeal wall (streptatest), assessment of symptoms of acute tonsillopharyngitis on the McIsaac scale, severity of sore throat, difficulty swallowing, swelling of the throat, measurement of body temperature, assessment of the clinical global impression of the therapy, adherence to treatment, frequency of the adverse reactions before treatment, 3 days after the beginning of therapy and after the course completion (day 10). RESULTS: Recovery occurred in 96.6% of patients in group 1 according to examination on the 10th day of treatment and in 93.3% of patients in group 2. The rate of fever regression was higher in group 1 - on the 3rd day of treatment, normalization of temperature was observed in 36.6% and 30% of patients in the comparison group. Pain syndrome, symptoms of throat swelling and difficulty swallowing significantly (p<0.01) regressed by the 10th day in patients of both treatment groups. The incidence of adverse reactions on the 10th day of treatment in group 1 was 10%, in group 2 - 33.3% (p=0.03). CONCLUSION: Amoxicillin + Clavulanic acid EXPRESS has high therapeutic efficacy in the treatment of acute streptococcal tonsillopharyngitis, comparable to the Amoxiclav in film-coated tablets. At the same time, dispersible tablets of Amoxicillin + Clavulanic acid EXPRESS demonstrated a significantly higher safety profile compared to the simple tablet form.

Effect of impeller type on cellular morphology and production of clavulanic acid by Streptomyces clavuligerus.

It is essential to evaluate the effects of operating conditions in submerged cultures of filamentous microorganisms. In particular, the impeller type influences the flow pattern, power consumption, and energy dissipation, leading to differences in the hydrodynamic environment that affect the morphology of the microorganism. This work investigated the effect of different impeller types, namely the Rushton turbine (RT-RT) and Elephant Ear impellers in up-pumping (EEUP) and down-pumping (EEDP) modes, on cellular morphology and clavulanic acid (CA) production by Streptomyces clavuligerus in a stirred-tank bioreactor. At 800 rpm and 0.5 vvm, the cultivations performed using RT-RT and EEUP impellers provided higher shear conditions and oxygen transfer rates than those observed with EEDP. These conditions resulted in higher clavulanic acid production using RT-RT (380.7 mg/L) and EEUP (453.3 mg/L) impellers, compared to EEDP (196.6 mg/L). Although the maximum CA concentration exhibited the same order of magnitude for RT-RT and EEUP impellers, the latter presented 40% of the specific power consumption (4.9 kW/m3) compared to the classical RT-RT (12.0 kW/m3). The specific energy for CA production ( E CA ), defined as the energy cost to produce 1 mg of CA, was 3.5 times lower using the EEUP impeller (1.91 kJ/mgCA) when compared to RT-RT (5.91 kJ/mgCA). Besides, the specific energy for O2 transfer ( E O 2 ), the energy required to transfer 1 mmol of O2, was 2.3 times lower comparing the EEUP impeller (3.28 kJ/mmolO2) to RT-RT (7.65 kJ/mmolO2). The results demonstrated the importance of choosing the most suitable impeller configuration in conventional bioreactors to manufacture bioproducts.

Clavulanic Acid Decreases Cocaine Cue Reactivity in Addiction-Related Brain Areas, a Randomized fMRI Pilot Study.

Background: Preclinical studies show that clavulanic acid (CLAV) inhibits cocaine self-administration. This study investigates the effect of CLAV on regions of brain activation in response to cocaine cues during functional magnetic resonance imaging (fMRI) in participants with cocaine use disorder (CUD). Methods: A double-masked, placebo-controlled clinical trial with thirteen individuals with severe CUD who were randomized to treatment with CLAV (N = 10, 9 completers) 500 mg/day or matched placebo (PBO) (N = 3) for 3 days. fMRI was used to assess brain reactivity to 18 alternating six-second video clips of cocaine or neutral scenes. In this paradigm, participants were exposed to three different stimulus conditions: NEUTRAL, WATCH (passive watching), and DOWN (actively inhibiting craving while watching). Results: Participants who received CLAV demonstrated a significant reduction in brain activity in the anterior cingulate gyrus (p = 0.009) and the caudate (p = 0.018) in response to DOWN cocaine cues. There was a trend toward lessened cue reactivity in other regions implicated in CUD. Conclusion: CLAV reduced the response of the brain regions associated with motivation and emotional response during the DOWN condition compared to PBO, suggesting CLAV may strengthen voluntary efforts to avoid cocaine use. This pilot data supports the use of CLAV for CUD. (Trial registered in ClinicalTrials.gov NCT04411914).

Embryonic Amoxicillin Exposure Has Limited Impact on Liver Development but Increases Susceptibility to NAFLD in Zebrafish Larvae.

Amoxicillin is commonly used in clinical settings to target bacterial infection and is frequently prescribed during pregnancy. Investigations into its developmental toxicity and effects on disease susceptibility are not comprehensive. Our present study examined the effects of embryonic amoxicillin exposure on liver development and function, especially the effects on susceptibility to non-alcoholic fatty liver disease (NAFLD) using zebrafish as an animal model. We discovered that embryonic amoxicillin exposure did not compromise liver development, nor did it induce liver toxicity. However, co-treatment of amoxicillin and clavulanic acid diminished BESP expression, caused bile stasis and induced liver toxicity. Embryonic amoxicillin exposure resulted in elevated expression of lipid synthesis genes and exacerbated hepatic steatosis in a fructose-induced NAFLD model, indicating embryonic amoxicillin exposure increased susceptibility to NAFLD in zebrafish larvae. In summary, this research broadens our understanding of the risks of amoxicillin usage during pregnancy and provides evidence for the impact of embryonic amoxicillin exposure on disease susceptibility in offspring.

Clavulanic acid sensitization seems more involved in cutaneous than systemic reactions in amoxicilline-clavulanate drug reactions.

Summary: BLs allergy is considered a major health issue, as BLs are the most frequently involved in drug allergic reactions. Amoxicillin (AX) is the most frequently involved drug in sensitization among all BLs. AX is commercialized alone or combined to clavulanic acid (CLA) in order to increase the antibiotic spectrum. The growing prescriptions of AX-CLA formulations contributed to increase the role of CLA as an allergy inducer. At present, little is known about the clinical characteristics of hypersensitivity reactions to clavulanate. The aim of this study was to assess the difference in the prevalence of cutaneous vs systemic reactions in patients who had a documented history of allergic reactions to amoxicillin-clavulanate and tested positive for clavulanate or penicillin/amoxicillin. Our study suggests that patients who presented only muco-cutaneous reactions were more often sensitized to CLA rather than AX.

Comprehensive stability analysis of 13 ß-lactams and ß-lactamase inhibitors in in vitro media, and novel supplement dosing strategy to mitigate thermal drug degradation.

Non-clinical antibiotic development relies on in vitro susceptibility and infection model studies. Validating the achievement of the targeted drug concentrations is essential to avoid under-estimation of drug effects and over-estimation of resistance emergence. While certain ß-lactams (e.g., imipenem) and ß-lactamase inhibitors (BLIs; clavulanic acid) are believed to be relatively unstable, limited tangible data on their stability in commonly used in vitro media are known. We aimed to determine the thermal stability of 10 ß-lactams and 3 BLIs via LC-MS/MS in cation-adjusted Mueller Hinton broth at 25 and 36°C as well as agar at 4 and 37°C, and in water at -20, 4, and 25°C. Supplement dosing algorithms were developed to achieve broth concentrations close to their target over 24 h. During incubation in broth (pH 7.25)/agar, degradation half-lives were 16.9/21.8 h for imipenem, 20.7/31.6 h for biapenem, 29.0 h for clavulanic acid (studied in broth only), 23.1/71.6 h for cefsulodin, 40.6/57.9 h for doripenem, 46.5/64.6 h for meropenem, 50.8/97.7 h for cefepime, 61.5/99.5 h for piperacillin, and >120 h for all other compounds. Broth stability decreased at higher pH. All drugs were ≥90% stable for 72 h in agar at 4°C. Degradation half-lives in water at 25°C were >200 h for all drugs except imipenem (14.7 h, at 1,000 mg/L) and doripenem (59.5 h). One imipenem supplement dose allowed concentrations to stay within ±31% of their target concentration. This study provides comprehensive stability data on ß-lactams and BLIs in relevant in vitro media using LC-MS/MS. Future studies are warranted applying these data to antimicrobial susceptibility testing and assessing the impact of ß-lactamase-related degradation.

Combinational antimicrobial activity of biogenic TiO2 NP/ZnO NPs nanoantibiotics and amoxicillin-clavulanic acid against MDR-pathogens.

The development of effective strategies against multidrug-resistant (MDR) pathogens is an urgent need in modern medicine. Nanoantibiotics (nABs) offer a new hope in countering the surge of MDR-pathogens. The aim of the current study was to evaluate the antibacterial activity of two attractive nABs, TiO2 NPs and ZnO NPs, and their performance in improving the antimicrobial activity of defined antibiotics (amoxicillin-clavulanic acid, amox-clav) against MDR-pathogens. The nABs were synthesized using a green method. The physicochemical characteristics of the synthesized nanoparticles were determined using standard methods. The results showed the formation of pure anatase TiO2 NPs and hexagonal ZnO NPs with an average particle size of 38.65 nm and 57.87 nm, respectively. The values of zeta potential indicated the high stability of the samples. At 8 mg/mL, both nABs exhibited 100 % antioxidant activity, while ZnO showed significantly higher activity at lower concentrations. The antibiofilm assay showed that both nABs could inhibit the formation of biofilms of Acinetobacter baumannii 80 and Escherichia coli 27G (MDR-isolates). However, ZnO NPs showed superior antibiofilm activity (100 %) against E. coli 27G. The MIC values were determined to be 8 (1), 2 (2), and 4 (4) mg/mL for amox-clav, TiO2 NPs, and ZnO NPs against A. baumannii 80 (E. coli 27G), respectively. The results showed that both nABs had synergistically enhanced antibacterial performance in combination with amox-clav. Specifically, an 8-fold reduction in MIC values of antibiotics was observed when they were combined with nABs. These findings highlight the potential of TiO2 NPs and ZnO NPs as effective nanoantibiotics against MDR-pathogens. The synergistic effect observed when combining nABs with antibiotics suggests a promising approach for combating antibiotic resistance. Further research and development in this area could lead to the development of more effective treatment strategies against MDR infections.

Clinical chorioamnionitis at term: definition, pathogenesis, microbiology, diagnosis, and treatment.

Clinical chorioamnionitis, the most common infection-related diagnosis in labor and delivery units, is an antecedent of puerperal infection and neonatal sepsis. The condition is suspected when intrapartum fever is associated with two other maternal and fetal signs of local or systemic inflammation (eg, maternal tachycardia, uterine tenderness, maternal leukocytosis, malodorous vaginal discharge or amniotic fluid, and fetal tachycardia). Clinical chorioamnionitis is a syndrome caused by intraamniotic infection, sterile intraamniotic inflammation (inflammation without bacteria), or systemic maternal inflammation induced by epidural analgesia. In cases of uncertainty, a definitive diagnosis can be made by analyzing amniotic fluid with methods to detect bacteria (Gram stain, culture, or microbial nucleic acid) and inflammation (white blood cell count, glucose concentration, interleukin-6, interleukin-8, matrix metalloproteinase-8). The most common microorganisms are Ureaplasma species, and polymicrobial infections occur in 70% of cases. The fetal attack rate is low, and the rate of positive neonatal blood cultures ranges between 0.2% and 4%. Intrapartum antibiotic administration is the standard treatment to reduce neonatal sepsis. Treatment with ampicillin and gentamicin have been recommended by professional societies, although other antibiotic regimens, eg, cephalosporins, have been used. Given the importance of Ureaplasma species as a cause of intraamniotic infection, consideration needs to be given to the administration of antimicrobial agents effective against these microorganisms such as azithromycin or clarithromycin. We have used the combination of ceftriaxone, clarithromycin, and metronidazole, which has been shown to eradicate intraamniotic infection with microbiologic studies. Routine testing of neonates born to affected mothers for genital mycoplasmas could improve the detection of neonatal sepsis. Clinical chorioamnionitis is associated with decreased uterine activity, failure to progress in labor, and postpartum hemorrhage; however, clinical chorioamnionitis by itself is not an indication for cesarean delivery. Oxytocin is often administered for labor augmentation, and it is prudent to have uterotonic agents at hand to manage postpartum hemorrhage. Infants born to mothers with clinical chorioamnionitis near term are at risk for early-onset neonatal sepsis and for long-term disability such as cerebral palsy. A frontier is the noninvasive assessment of amniotic fluid to diagnose intraamniotic inflammation with a transcervical amniotic fluid collector and a rapid bedside test for IL-8 for patients with ruptured membranes. This approach promises to improve diagnostic accuracy and to provide a basis for antimicrobial administration.

Amoxicillin Induced Fever, Rash, and Catatonia - A Case Study.

INTRODUCTION: Adverse drug reactions (ADR) are defined as any harmful or unpleasant events or injuries resulting from the use of any particular drug. Among those antibiotics that cause adverse reactions, amoxicillin is one of them. Catatonia and vasculitic rash are its rare adverse effects. CASE PRESENTATION: A 23-year-old postpartum female, with a history of taking empirical Amoxiclav (amoxicillin-clavulanic acid 625 mg) injection and oral tablets for episiotomy wound, presented with altered sensorium and fever followed by maculopapular rash. On examination, she had generalized rigidity with waxy flexibility that improved by lorazepam challenge and was diagnosed as catatonia. On evaluation, amoxicillin was found to be precipitating catatonia in this patient. CONCLUSION: Since the diagnosis of catatonia is often missed, any cases with clinical presentation of fever, rash, altered sensorium, and generalized rigidity should also be suspected for druginduced ADR and the precipitating factor should be searched for.

Efficacy of antimicrobial and nutraceutical treatment for canine acute diarrhoea: A systematic review and meta-analysis for European Network for Optimization of Antimicrobial Therapy (ENOVAT) guidelines.

Systemic antimicrobial treatments are commonly prescribed to dogs with acute diarrhoea, while nutraceuticals (prebiotics, probiotics, and synbiotics) are frequently administered as an alternative treatment. The aim of this systematic review and meta-analysis was to assess the effectiveness of antimicrobials and nutraceutical preparations for treatment of canine acute diarrhoea (CAD). The results of this study will be used to create evidence-based treatment guidelines. PICOs (population, intervention, comparator, and outcome) were generated by a multidisciplinary expert panel taking into account opinions from stakeholders (general practitioners and dog owners). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to evaluate the certainty of the evidence. The systematic search yielded six randomised controlled trials (RCT) for antimicrobial treatment and six RCTs for nutraceutical treatment meeting the eligibility criteria. Categories of disease severity (mild, moderate, and severe) were created based on the presence of systemic signs and response to fluid therapy. Outcomes included duration of diarrhoea, duration of hospitalization, progression of disease, mortality, and adverse effects. High certainty evidence showed that antimicrobial treatment did not have a clinically relevant effect on any outcome in dogs with mild or moderate disease. Certainty of evidence was low for dogs with severe disease. Nutraceutical products did not show a clinically significant effect in shortening the duration of diarrhoea (based on very low to moderate certainty evidence). No adverse effects were reported in any of the studies.