[Bacterial Conjunctivitis: Current Aspects of Diagnosis and Therapy]. / Bakterielle Konjunktivitis: Aktuelle Aspekte der Diagnostik und Therapie.

Bacterial conjunctivitis is a leading cause of infectious conjunctivitis in children and second most common cause in adults. Although often self-limiting, it can lead to complications like corneal scarring and systemic infections in high-risk groups including newborns and immunocompromised patients. Thus, prompt diagnosis and treatment are essential for these vulnerable populations. Common bacterial causes are Staphylococcus aureus and Streptococcus pneumoniae in adults and Haemophilus influenzae and Moraxella catarrhalis in children. Clinical features alone do not reliably identify the causative pathogen. Microbiological testing is necessary for persistent or severe cases. Topical antibiotics like azithromycin or fluorochinolones are usually prescribed. However, gonococcal and chlamydial conjunctivitis warrant systemic antibiotics due to their potential for severe complications. Increasing antibiotic resistance might even necessitate tailored therapy based on antibiotic susceptibility profiles. Screening and treating pregnant women is an effective prevention strategy by reducing perinatal transmission (especially of gonococcal and chlamydial infections). In summary, while often self-limiting, potential complications and rising antibiotic resistance underscore the importance of timely diagnosis and treatment of bacterial conjunctivitis. Preventive measures including maternal screening are crucial public health initiatives to curb the risks associated with this common eye infection.

Clinical Presentations and Treatment Outcomes of Mycoplasma genitalium Infections at a Large New York City Health Care System.

BACKGROUND: Mycoplasma genitalium (MG) is an emerging sexually transmitted infection. Treatment of MG is complicated by increasing resistance to primary treatment regimens, including macrolides and fluoroquinolones. Understanding the various clinical presentations and relative effectiveness of treatments for MG is crucial to optimizing care. METHODS: Patients with a positive MG nucleic acid amplification test between July 1, 2019, and June 30, 2021, at a large health system in New York City were included in a retrospective cohort. Demographics, clinical presentations, coinfections, treatment, and follow-up microbiologic tests were obtained from the electronic medical record. Associations with microbiologic cure were evaluated in bivariate and multivariable logistic regression models. RESULTS: Five hundred two unique patients had a positive MG nucleic acid amplification test result during the study period. Male individuals presented predominantly with urethritis (117 of 187 [63%]) and female individuals with vaginal symptoms (142 of 315 [45%]). Among patients with follow-up testing who received a single antibiotic at the time of treatment, 43% (90 of 210) had persistent infection and 57% (120 of 210) had microbiologic cure. Eighty-two percent of patients treated with moxifloxacin had microbiologic cure compared with 41% of patients receiving azithromycin regimens ( P < 0.001). In multivariable analysis, treatment with moxifloxacin was associated with 4 times the odds of microbiologic cure relative to low-dose azithromycin (adjusted odds ratio [aOR], 4.18; 95% confidence interval, 1.73-10.13; P < 0.01). CONCLUSIONS: Clinical presentations of MG vary, with urethritis or vaginal symptoms in most cases. Among patients who received a single antibiotic, only treatment with moxifloxacin was significantly associated with microbiologic cure relative to low-dose azithromycin.

The Use of Antimicrobial Drug in Patients During the COVID-19 Pandemic: A Meta-Analysis.

Objective: To analyze the use of antimicrobial drugs in patients during the COVID-19 pandemic. Methods: We searched for literature about antimicrobial treatment in COVID-19 patients through the Cochrane Library, Embase, PubMed, the Chinese biomedical literature database, CNKI, the Chinese journal full-text database, Wanfang, and Vipu. The quality evaluation of the literature was performed by Jadad's quality score. Results: A total of three articles reported on ivermectin treatment in patients with COVID-19, and the Meta-analysis showed no clinical and statistical heterogeneity among the studies (I2 = 15%, P = .31), a fixed effect model was used to incorporate effect sizes. The clinical effect of the observed group was not different from the control group (P = .16). None of the three ivermectin articles with clinical effect as the effect indicator showed a significant difference (P > .05), suggesting no publication bias. A total of four publications reported the treatment with azithromycin in patients with COVID-19, and the Meta-analysis showed no clinical and statistical heterogeneity between the studies (I2 = 0%, P = .88), using a fixed-effect model to incorporate the effect sizes. The clinical effect of the observed group was not different from the control group (P = .57). None of the four azithromycin articles with a clinical effect as the effect index was statistically significant (P > .05), suggesting no publication bias. Conclusion: During the COVID-19 pandemic, the patient's use of antibiotics does not significantly improve clinical efficacy, so antibiotic use is recommended only for patients with complicated bacterial infections.

Comparative study evaluating the efficacy of topical azithromycin versus oral doxycycline in the treatment of meibomian gland dysfunction.

Objective: To assess the efficacy of topical azithromycin drops versus oral doxycycline therapy in meibomian gland dysfunction. METHODS: The prospective randomised trial was conducted from December 2019 to June 2020 at the Qazi Hussain Ahmad Medical Complex, Nowshera, Pakistan, and comprised patients of either gender aged 26-42 years having long-standing posterior blepharitis / meibomian gland dysfunction. The subjects were randomised into two equal groups. Both the groups were advised to do warm compresses and lid massage three times a day for 5 min. each for 4 weeks. In addition, group A received azithromycin 1% drops 2 times/day for 1 week, followed by once a day for 3 weeks, while group B received oral doxycycline 100mg once a day for 4 weeks. Baseline, midstream at 2 weeks and post-intervention status, including subjective symptoms, were compared. RESULTS: Of the 60 subjects enrolled, there were 30(50%) in each of the two groups; 32(53.3%) males and 28(46.4%) females. While all 30(100%) the participants in group A completed the trial without any adverse reaction to medication, 8(26.7%) in group B quit midstream owing to anorexia/nausea and gastrointestinal discomfort. Compared to baseline, reduction in both subjective and objective features of the disease in both groups were noted regardless of gender (p=0.08). No significant difference was evident in symptoms healing rate and improvement in foreign body sensation between the groups (p>0.05). Group A treatment improved eye redness, while group B proved better in respect of meibomian glands obstruction healing and corneal staining p<0.05). Conclusion: Both topical azithromycin and oral doxycycline were effective and had their own edge as far as symptomatic improvement was concerned in the treatment of meibomian gland dysfunction.

Clinical efficacy of Azithromycin for COVID-19 management: A systematic meta-analysis of meta-analyses.

BACKGROUND: Azithromycin has been adopted as a component of the COVID-19 management protocol throughout the global healthcare settings but with a questionable if not downright unsubstantiated evidence base. OBJECTIVES: In order to amalgamate and critically appraise the conflicting evidence around the clinical efficacy of Azithromycin (AZO) vis a vis COVID-19 management outcomes, a meta-analysis of meta-analyses was carried out to establish an evidence-based holistic status of AZO vis a vis its efficacy as a component-in-use of the COVID-19 management protocol. METHODS: A comprehensive systematic search was carried out through PubMed/Medline, Cochrane and Epistemonikos with a subsequent appraisal of abstracts and full-texts, as required. The Quality of Reporting of Meta-analyses (QUOROM) checklist and the Assessment of Multiple Systematic Reviews (AMSTAR) methodology were adopted to assess the methodological quality of the included meta-analyses. Random-effects models were developed to calculate summarized pool Odds Ratios (with 95% confidence interval) for the afore determined primary and secondary outcomes. RESULTS: AZO, when compared with best available therapy (BAT) including or excluding Hydroxychloroquine, exhibited statistically insignificant reduction in mortality [(n= 27,204 patients) OR= 0.77 (95% CI: 0.51-1.16) (I2= 97%)], requirement of mechanical ventilation [(n= 14,908 patients) OR= 1.4 (95% CI: 0.58-3.35) (I2= 98%)], induction of arrhythmia [(n= 9,723 patients) OR= 1.21 (95% CI: 0.63-2.32) (I2= 92%)] and QTc prolongation (a surrogate for torsadogenic effect) [(n= 6,534 patients) OR= 0.62 (95% CI: 0.23-1.73) (I2= 96%)]. CONCLUSION: The meta-analysis of meta-analyses portrays AZO as a pharmacological agent that does not appear to have a comparatively superior clinical efficacy than BAT when it comes to COVID-19 management. Secondary to a very real threat of anti-bacterial resistance, it is suggested that AZO be discontinued and removed from COVID-19 management protocols.

Role of streptococcal infection in the etiopathogenesis of pityriasis lichenoides chronica and the therapeutic efficacy of azithromycin: a randomized controlled trial.

The exact aetiology of pityriasis lichenoides chronica (PLC) remains unknown. While phototherapy is the most investigated therapeutic modality, azithromycin has been used scarcely. The aim of this study is to evaluate the therapeutic efficacy of azithromycin in the treatment of PLC compared to NB-UVB and evaluating the presence of streptococcal infection as a possible etiological factor in PLC patients. The study was designed as a randomised controlled trial. Twenty-four patients with PLC were randomly allocated into either azithromycin (n = 13, standard dose every 10 days) or NB-UVB (n = 11, thrice weekly) groups. End of study (EOS) was either complete clearance of lesions or a maximum of 8 weeks. Therapeutic efficacy was defined as percent reduction in lesions and was calculated for the rash as a whole, erythematous papules alone, and hypopigmented lesions alone and graded into complete, very-good, good, poor or no response. Anti-streptolysin O titre (ASOT), anti-deoxyribonuclease B titre (anti-DNaseB) and throat culture were evaluated at day 0. No significant difference existed between both groups as regards therapeutic efficacy. At EOS, NB-UVB achieved significantly more percent reduction in the extent of hypopigmented lesions and consequently in the rash as a whole (p = 0.001, p = 0.034, respectively). The extent of the rash as a whole was significantly less in the NB-UVB at EOS (p = 0.029, respectively). The effect of NB-UVB on hypopigmented lesions appeared early at week 4 of treatment. Only two patients, one from each group, relapsed during the 3 month follow-up. Evidence of recent streptococcal infection was present in 79% of the cases, mainly in the form of elevated ASOT (94.7%). It was significantly more encountered in young children (< 13 years) (p = 0.03) and was associated with more extent of erythematous papules and consequently with more extent of the rash as a whole (p = 0.05 and p = 0.01, respectively). It did not affect outcome of therapy at EOS. Azithromycin did not show more favorable response in patients with recent streptococcal infection. Therapeutic efficacy of azithromycin is comparable to NB-UVB in treatment of PLC; however, NB-UVB is superior in management of hypopigmented lesions. It is highly suggested that PLC could be a post streptococcal immune mediated disorder.Registration number: ClinicalTrials.gov, NCT03831269.

Paediatric ocular rosacea: diagnosis and management with an eyelid-warming device and topical azithromycin 1.5.

BACKGROUND: Ocular rosacea is a chronic inflammatory disorder with periods of exacerbation and remission, often underdiagnosed in children. When diagnosed, its management is challenging because of a lack of effective long-term treatment options. OBJECTIVE: To report our experience in cases of pediatric ocular rosacea treated with moist heat therapy and topical azithromycin 1.5%. METHODS: The medical records of six children diagnosed with ocular rosacea based on a careful medical history and slit-lamp examination of the eyelids and ocular surface were reviewed. Previous treatments were discontinued, and children/parents were instructed to use the eyelid-warming device for 1 or 2 sessions of 10minutes each day, followed by eyelid massage and cleansing, in combination with azithromycin 1.5% eye drops. RESULTS: The diagnosis of ocular rosacea in these children was delayed for several months or years from the first identifiable clinical sign or symptom. All the children presented with corneal sequelae and decreased vision. Ocular manifestations included meibomian gland disease, recurrent chalazia, and phlyctenular keratoconjunctivitis. Cutaneous signs were not always associated with the condition. Ocular rosacea was usually resistant to initial treatments with antibiotics and topical corticosteroids. Treatment with the eyelid-warming device in combination with azithromycin 1.5% led to a rapid improvement in the clinical signs and was well tolerated by all patients. CONCLUSIONS: Childhood ocular rosacea is potentially sight threatening. Practitioners should consider this condition in order to minimise diagnostic delay and subsequent complications. Combined therapy of eyelid hygiene (including an eyelid warming device) and azithromycin 1.5% eye drops was effective in treating ocular rosacea in children.

Clinical Evaluation and Exploration of Mechanisms for Modified Xiebai Powder or Modified Xiebai Powder Combined with Western Medicine in the Treatment of Pneumonia.

Objective: To systematically evaluate the clinical efficacy of modified Xiebai Powder or modified Xiebai Powder combined with Western medicine in the treatment of pneumonia and explore its potential mechanism of action. Methods: Meta-analysis was used to screen the eligible literature on randomized controlled trials (RCTs) about Xiebai Powder in the treatment of pneumonia, and Review Manager 5.3 software was used for statistical analysis of the data. Based on the results of the meta-analysis, the active ingredients in Xiebai Powder and their therapeutic targets, disease-related targets, and intersection targets were screened using methods of network pharmacology, and their biological processes and key signaling pathways were analyzed using bioinformatics tools. Molecular docking was carried out to verify and predict the mechanisms for Xiebai Powder combined with Western medicine in the treatment of pneumonia. Results: A total of 16 papers were screened out, with a total of 1,465 patients. The results of the meta-analysis showed that modified Xiebai Powder or modified Xiebai Powder combined with Western medicine were superior to conventional Western medicine in terms of clinical efficacy, shortening the disappearance time of symptoms (body temperature, cough, and pulmonary rales) and reducing the level of C-reactive protein, and the incidence of adverse reactions was significantly reduced. A total of 40 active ingredients in Xiebai Powder and 285 therapeutic targets of Xiebai Powder combined with azithromycin after deduplication were screened out from the database. KEGG enrichment analysis showed that Xiebai Powder combined with azithromycin might play a role in the treatment of pneumonia through the IL-17 signaling pathway, tumor necrosis factor signaling pathway, C-type lectin receptor signaling pathway, Toll-like receptor signaling pathway, and HIF-1 signaling pathway. Conclusions: Modified Xiebai Powder or modified Xiebai Powder combined with azithromycin has better effects in treating pneumonia, and modified Xiebai Powder combined with azithromycin may play a role in treating pneumonia through several pathways such as the IL-17 signaling pathway.

A comparison of different antibiotic regimens for the treatment of naturally acquired shigellosis in rhesus and pigtailed macaques (Macaca mulatta and nemestrina).

BACKGROUND: Shigella spp. are common enteric pathogens in captive non-human primates. Treatment of symptomatic infections involves supportive care and antibiotic therapy, typically with an empirical choice of antibiotic. METHODS: Twenty-four clinically ill, Shigella PCR-positive animals were randomly assigned to one of four treatment groups: single-dose ceftiofur crystalline free acid (CCFA), single-dose azithromycin gavage, a 5-day tapering azithromycin dose, or 7-day course of enrofloxacin. We hypothesized that all antimicrobial therapies would have similar efficacy. RESULTS: Animals in all groups cleared Shigella, based on fecal PCR, and had resolution of clinical signs 2 weeks after treatment. Eight out of nine clinically ill and PCR-positive animals tested negative by fecal culture. CONCLUSIONS: Single-dose CCFA, single-dose azithromycin, and a 5-day tapering course of azithromycin all performed as well as a 7-day course of enrofloxacin in eliminating Shigella infection. Fecal PCR may be a better diagnostic than culture for Shigella.

Model for Evaluating Antimicrobial Therapy To Prevent Life-Threatening Bacterial Infections following Exposure to a Medically Significant Radiation Dose.

More evidence is needed to support recommendations for medical management of acute radiation syndrome (ARS) and associated infections resulting from a radiological/nuclear event. While current guidelines recommend the administration of antibiotics to chemotherapy patients with febrile neutropenia, the clinical benefit is unclear for acute radiation injury patients. A well-characterized nonhuman primate (NHP) model of hematopoietic ARS was developed that incorporates supportive care postirradiation. This model evaluated the efficacy of myeloid growth factors within 24 to 48 h after total body irradiation (TBI). However, in this model, NHPs continued to develop life-threatening bacterial infections, even when granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor was administered in combination with antibiotic monotherapy. In this study, we evaluated the efficacy of combination antibiotic therapies administered to NHPs following 7.4-Gy TBI to understand the occurrence of bacterial infection in NHPs with hematopoietic ARS. We compared enrofloxacin-linezolid, enrofloxacin-cefepime, and enrofloxacin-ertapenem to enrofloxacin monotherapy. The primary endpoint was 60-day postirradiation mortality, with secondary endpoints of overall survival time, incidence of bacterial infection, and bacteriologic culture with antimicrobial susceptibility testing. We observed that enrofloxacin-ertapenem significantly increased survival compared to enrofloxacin monotherapy. Bacteria isolated from nonsurviving macaques with systemic bacterial infections exhibited uniform resistance to enrofloxacin and variable resistance to beta-lactam antibiotics, linezolid, gentamicin, and azithromycin. Multidrug antibiotic resistance was observed in Enterococcus spp. and Escherichia coli. We conclude that antibiotic combination therapies appear to be more effective than monotherapy alone but acknowledge that more work is needed to identify an optimal antimicrobial therapy.

Zwitterionic meso-silica/polypeptide hybrid nanoparticles for efficient azithromycin delivery and photodynamic therapy for synergistic treatment of drug-resistant bacterial infection.

The treatment of drug-resistant bacterial infections attributed to the overuse of antibiotics still remains a serious challenge globally. Herein, zwitterionic charge switchable meso-silica/polypeptide hybrid nanoparticles (MSPNs) were prepared for the synergistic chemo-photodynamic therapy in the treatment of drug-resistant bacterial infections. Subsequently, azithromycin (AZT) and methylene blue (MB) were loaded in the MSPNs to form the combined chemo-photodynamic therapeutic nanoparticles (MSPNs-AZT/MB) for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Remarkably, the as-prepared MSPNs-AZT/MB exhibited a negative surface charge of -5.2 mV at physiological pH while switching into positive surface charge of 24.7 mv in an acidic environment, leading to enhanced binding with bacterial surface. The lipase-triggered AZT release up to 77.9 % was achieved, and the loaded MB demonstrated efficient singlet oxygen (1O2) generation for photodynamic therapy. The in vitro experimental results displayed an excellent antibacterial effect against MRSA in both planktonic and biofilm phenotypes. Additionally, the as-prepared MSPNs-AZT/MB exhibited synergistic and enhanced antibacterial infection effect up to 94 % comparing to monotherapy in a mice model. Considering the above advantages, the as-prepared combined chemo-photodynamic therapeutic nanoparticles showed promising biocompatibility and clinical potential for the efficient therapy of drug-resistant bacteria.

Combination effect of azithromycin with TCM preparation Xiyanping injection against Klebsiella pneumoniae infection in rats.

BACKGROUND: Klebsiella pneumoniae is known as one of the most principal opportunistic human pathogens. Although antibiotics such as the first-line agent azithromycin (AZM) usually are efficient for the treatment of K. pneumonia-related infections, growing threat from antibiotic resistance has become a major challenge. Various preparations based on traditional Chinese medicine (TCM) clinical experience have been developed to help combat such a global public health threat, including Xiyanping injection (XYP) that is made from the natural product andrographolide with potent heat-clearing and toxin-resolving functions. PURPOSE: The present study aimed to demonstrate the therapeutic potential, as well as the action of mechanism of AZM in combination with XYP against K. pneumonia infection in rats. METHODS: Pneumonia model of K. pneumoniae infection in rats was established and subjected to various treatments. The lung histopathological lesions were evaluated. ELISA and Griess techniques were used to determine the level of crucial cytokines. The protein expressions of MAPKs and NF-κB pathways were analyzed by Western blotting. RESULTS: The combination in vivo could significantly inhibit the proliferation of K. pneumoniae in lung, improve the pathological changes of lung and reduce inflammatory factors in lung homogenate and bronchoalveolar lavage fluid, mainly by inactivating MAPKs and NF-κB signaling pathways. Combination therapy caused one-fold increase in apparent distribution volume of AZM in rats after multiple dosing, along with a significant increase of AZM level in lungs but obvious decrease in livers. CONCLUSION: The combination therapy of AZM and XYP showed increased antibacterial and anti-inflammatory properties, indicating that it might be used to treat K. pneumoniae infection.

Antibiotic therapy does not alter mitochondrial bioenergetics in lymphocytes of patients with septic shock - A prospective cohort study.

Antibiotics may trigger alterations in mitochondrial function, which has been explored in cells culture, and in animal model of sepsis. This study sought to evaluate whether antibiotic therapy affects mitochondrial bioenergetics in a 68-patients clinical study. We studied mitochondrial respiratory rates at two time points: the first day of antibiotic administration and three days after. The Δbasal, ΔCI, ΔCII respiration, and ΔBCE respiratory rates were not different between patients administered with polymyxin, vancomycin, amoxicillin-clavulanate, and azithromycin compared to those who were not administered. Specific beta-lactams are associated with specific modifications in mitochondrial respiratory endpoints - patients who used meropenem had higher delta C2 values compared to those who did not (p = 0.03). Patients who used piperacillin-tazobactam had lower delta C1 (p = 0.03) values than those who did not, but higher delta C2 values (p = 0.02). These mitochondrial metabolic signatures in isolated lymphocytes challenges the proposed effects of antibiotics in mitochondrial bioenergetics of cell cultures, but at current status have an uncertain clinical significance.

Multi-drug-resistant chronic endometritis in infertile women with repeated implantation failure: trend over the decade and pilot study for third-line oral antibiotic treatment.

PURPOSE: To evaluate the yearly prevalence and annual transition of multi-drug-resistant-chronic endometritis (MDR-CE) in infertile women with a history of repeated implantation failure (RIF) and to establish the third-line antibiotic treatment regimen against MDR-CE. METHODS: This retrospective/prospective cohort and pilot study included 3473 RIF women between April 2010 and September 2021. The endometrial stromal plasmacyte density index (ESPDI) was calculated in 3449 CD138-immunostained endometrial sections to evaluate CE. The microbiota in the vaginal secretions and endometrial fluid was compared between 17 patients with MDR-CE and 16 patients with antibiotics-sensitive CE. In a pilot study, oral moxifloxacin (400 mg/day, 10 days, n = 24) or azithromycin (500 mg/day, 3 days, n = 24) was administered to eligible patients with MDR-CE. RESULTS: From April 2010 to March 2020, CE was detected in 31.4% of RIF women and MDR was detected in 7.8% of CE. While the prevalence of CE was stable for a decade, MDR in CE increased steadily (OR 8.27, 95% CI 2.58-26.43, p trend < 0.001). The bacterial species/communities unique to MDR-CE were not found. The histopathologic cure rate of MDR-CE was similar between the moxifloxacin and azithromycin groups (79.2% vs 75.0%, OR 1.27, 95% CI 0.32-4.89, p value 0.73), as well as reproductive outcomes in subsequent embryo transfer cycles. CONCLUSION: In RIF women, MDR in CE increased over the decade. As a third-line treatment for MDR-CE, azithromycin may have a clinical advantage due to its shorter time administration periods. CLINICAL TRIAL NUMBER: ClinicalTrials.gov Identifier: UMIN-CTR 000029449/000031909.

Case Report: Whole-Genome Sequencing of Serially Collected Haemophilus influenzae From a Patient With Common Variable Immunodeficiency Reveals Within-Host Evolution of Resistance to Trimethoprim-Sulfamethoxazole and Azithromycin After Prolonged Treatment With These Antibiotics.

We report within-host evolution of antibiotic resistance to trimethoprim-sulfamethoxazole and azithromycin in a nontypeable Haemophilus influenzae strain from a patient with common variable immunodeficiency (CVID), who received repeated or prolonged treatment with these antibiotics for recurrent respiratory tract infections. Whole-genome sequencing of three longitudinally collected sputum isolates during the period April 2016 to January 2018 revealed persistence of a strain of sequence type 2386. Reduced susceptibility to trimethoprim-sulfamethoxazole in the first two isolates was associated with mutations in genes encoding dihydrofolate reductase (folA) and its promotor region, dihydropteroate synthase (folP), and thymidylate synthase (thyA), while subsequent substitution of a single amino acid in dihydropteroate synthase (G225A) rendered high-level resistance in the third isolate from 2018. Azithromycin co-resistance in this isolate was associated with amino acid substitutions in 50S ribosomal proteins L4 (W59R) and L22 (G91D), possibly aided by a substitution in AcrB (A604E) of the AcrAB efflux pump. All three isolates were resistant to aminopenicillins and cefotaxime due to TEM-1B beta-lactamase and identical alterations in penicillin-binding protein 3. Further resistance development to trimethoprim-sulfamethoxazole and azithromycin resulted in a multidrug-resistant phenotype. Evolution of multidrug resistance due to horizontal gene transfer and/or spontaneous mutations, along with selection of resistant subpopulations is a particular risk in CVID and other patients requiring repeated and prolonged antibiotic treatment or prophylaxis. Such challenging situations call for careful antibiotic stewardship together with supportive and supplementary treatment. We describe the clinical and microbiological course of events in this case report and address the challenges encountered.

Efficacy and safety of Tanreqing injection combined with antibiotics against Streptococcus pneumoniae pneumonia: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Tanreqing injection (TRQ) is a traditional Chinese medicine injection. The goal of this study was to assess the clinical efficacy and safety of TRQ injection in combination with azithromycin or ceftriaxone, as well as azithromycin or ceftriaxone alone, in treating Streptococcus pneumoniae pneumonia (SPP). METHODS: The randomized controlled trial (RCT) of TRQ injection combined with antibiotics versus antibiotics alone in the treatment of SPP was retrieved from Chinese and English databases (the control group was treated with antibiotics alone, while the experimental group received TRQ injection combined with antibiotics). The retrieval period was from the database's inception through February 2022. The data was extracted using the Cochrane Collaboration Network Quality Evaluation Standards, the methodological quality of the included literature was assessed, and the outcome indicators were calculated using RevMan5.4.1 software. RESULTS AND DISCUSSION: A total of 25 RCTs were collected, including 2057 patients. TRQ injection combined with antibiotics significantly improved clinical efficacy and reduced defervescence time, lung rale disappearance time, cough disappearance time, disappearance time of chest pain, and average hospitalization time when compared to control group, according to meta-analysis results (p < 0.05). WHAT IS NEW AND CONCLUSION: In the treatment of SPP, TRQ injection combination with antibiotics can significantly improve the total effect rate when compared to standard western medicine. Due to the low quality of the randomized controlled trials included in this investigation, more high-quality, multi-center, large-sample, prospective, randomized, double-blind clinical studies are needed to confirm the aforementioned conclusions.

Extensively drug-resistant (XDR) Neisseria gonorrhoeae causing possible gonorrhoea treatment failure with ceftriaxone plus azithromycin in Austria, April 2022.

We describe a gonorrhoea case with ceftriaxone plus high-level azithromycin resistance. In April 2022, an Austrian heterosexual male was diagnosed with gonorrhoea after sexual intercourse with a female sex worker in Cambodia. Recommended treatment with ceftriaxone (1 g) plus azithromycin (1.5 g) possibly failed. Worryingly, this is the second strain in an Asian Neisseria gonorrhoeae genomic sublineage including high-level azithromycin-resistant strains that developed ceftriaxone resistance by acquisition of mosaic penA-60.001. Enhanced resistance surveillance and actions are imperative to prevent spread.

Study Effect of Azithromycin and Doxycycline in Mucus Producing and Inflammatory Signaling Pathways of Allergic Asthma.

Asthma is a respiratory disease; involving millions of people worldwide. The main cause of asthma is allergy and immune response dysregulation. The effects of azithromycin and doxycycline as asthma-controlling drugs were evaluated in this study. Mice asthma model was produced and asthmatic mice were treated with azithromycin (75 mg/kg, orally) and doxycycline (20 mg/kg, orally). Eosinophils and neutrophils count, interleukin (IL)-4, IL-5, IL-12, IL-13, and total immunoglobulin E (IgE) levels were measured. Histological study and evaluating the genes expression of Muc5ac, Muc5b, IL-33, COX2, MYD88, and TRAF6 were performed. Azithromycin and doxycycline did not affect eosinophil and neutrophil percentage, IL-4, IL-5, IL-12, and total IgE levels, peribronchial and perivascular inflammation, goblet cell hyperplasia, and gene expression of MYD88, TRAF6, and COX2. Treatment with azithromycin significantly decreased IL-13 level, mucus secretion, and gene expression of IL-33, Muc5ac, and Muc5b; compared to the non-treated asthma group. Azithromycin administration controls mucus secretion and inflammation. Azithromycin therapy and not doxycycline might be an effective adjuvant option in asthma with reducing mucus in the airway.

Azithromycin and high-dose vitamin D for treatment and prevention of asthma-like episodes in hospitalised preschool children: study protocol for a combined double-blind randomised controlled trial.

INTRODUCTION: Previous randomised controlled trials (RCTs) suggest antibiotics for treating episodes of asthma-like symptoms in preschool children. Further, high-dose vitamin D supplementation has been shown to reduce the rate of asthma exacerbations among adults with asthma, while RCTs in preschool children are lacking. The aims of this combined RCT are to evaluate treatment effect of azithromycin on episode duration and the preventive effect of high-dose vitamin D supplementation on subsequent episodes of asthma-like symptoms among hospitalised preschoolers. METHODS AND ANALYSIS: Eligible participants, 1-5 years old children with a history of recurrent asthma-like symptoms hospitalised due to an acute episode, will be randomly allocated 1:1 to azithromycin (10 mg/kg/day) or placebo for 3 days (n=250). Further, independent of the azithromycin intervention participants will be randomly allocated 1:1 to high-dose vitamin D (2000 IU/day+ standard dose 400 IU/day) or standard dose (400 IU/day) for 1 year (n=320). Participants are monitored with electronic diaries for asthma-like symptoms, asthma medication, adverse events and sick-leave. The primary outcome for the azithromycin intervention is duration of asthma-like symptoms after treatment. Secondary outcomes include duration of hospitalisation and antiasthmatic treatment. The primary outcome for the vitamin D intervention is the number of exacerbations during the treatment period. Secondary outcomes include time to first exacerbation, symptom burden, asthma medication and safety. ETHICS AND DISSEMINATION: The RCTs are approved by the Danish local ethical committee and conducted in accordance with the guiding principles of the Declaration of Helsinki. The Danish Medicines Agency has approved the azithromycin RCT, which is monitored by the local Unit for Good Clinical Practice. The vitamin D RCT has been reviewed and is not considered a medical intervention. Results will be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBERS: NCT05028153, NCT05043116.