Oral Azithromycin Research Articles

Successful treatment of Mycoplasma genitalium urethritis with high-dose tinidazole

Abstract A 30-year-old male patient with symptomatic Mycoplasma genitalium urethritis failed treatment with oral azithromycin, two-stage doxycycline-moxifloxacin, and minocycline. Molecular testing confirmed the presence of macrolide resistance mutations. Treatment with oral tinidazole 2 grams daily for seven days resulted in clinical and microbiologic cure.

Scrub typhus masquerading as acute acalculous cholecystitis in a child - a case report.

We describe a case of scrub typhus in a 12-year old boy who presented with symptoms mimicking acute acalculous cholecystitis. He tested positive for anti-scrub typhus IgM antibodies. Treatment with oral azithromycin led to significant improvement and resolution of symptoms. Thus it is important to consider scrub typhus as a differential diagnosis for an acute abdomen in endemic areas. Timely diagnosis may avoid unnecessary suffering.

Azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a phase II randomised controlled trial

BackgroundAfrican children with severe malaria are at increased risk of non-typhoidal salmonellae co-infection. Broad-spectrum antibiotics are recommended by guidelines but the optimal class and dose have not been established. We investigated the optimal dose of oral dispersible azithromycin and whether simple clinical criteria and point-of-care biomarkers could target antibiotics to those at greatest risk of bacterial co-infection.MethodsWe conducted a phase I/II trial in Ugandan children with severe malaria comparing a 5-day course of azithromycin: 10, 15 and 20 mg/kg of azithromycin (prescribed by weight bands) spanning the dose-range effective for other salmonellae infection. We generated relevant pharmacokinetic (PK) data by sparse sampling during dosing intervals and investigated associations between azithromycin exposure and potential mechanisms (PK-pharmacodynamics) using change in C-reactive protein (CRP), a putative marker of sepsis, at 72 h (continuous) and microbiological cure (7-day) (binary), alone and as a composite with 7-day and 90-day survival. To assess whether clinical or biomarkers could identify those at risk of sepsis, a non-severe malaria control was concurrently enrolled.ResultsBetween January 2020 and January 2022, 105 cases were randomised azithromycin doses: 35 to 10 mg/kg, 35 to 15 mg/kg and 35 to 20 mg/kg. Fifty non-severe malaria controls were concurrently enrolled. CRP reduced in all arms by 72 h with a mean reduction of 65.8 mg/L (95% CI 57.1, 74.5) in the 10 mg/kg arm, 64.8 mg/L (95% CI 56.5, 73.1; p = 0.87) in the 20 mg/kg arm and a smaller reduction 51.2 mg/L (95% CI 42.9, 59.5; p = 0.02) in the 15 mg/kg arm. Microbiological cure alone outcome was not analysed as only one pathogen was found among cases. Three events contributed to the composite outcome of 7-day survival and microbiological cure, with no events in the 15 mg/kg arm. The odds ratio comparing 20 vs 10 mg/kg was 0.50 (95% CI 0.04, 5.79); p = 0.58. Due to the low number of pathogens identified, it was not possible to identify better methods for targeting antibiotics including both the cases and controls.ConclusionsWe found no evidence for an association between systemic azithromycin exposure and reduction in CRP. Further work is needed to better identify children at highest risk from bacterial co-infection.Trial registrationISRCTN49726849 (registered on 27th October 2017).

Effect of oral doxycycline, azithromycin and isotretinoin on haematological inflammatory markers and interleukin-17A levels in acne vulgaris: a single blinded randomised interventional study.

Amidst the existing literature on the effect of isotretinoin on serum interleukin-17 levels in acne patients, the effects of oral antibiotics azithromycin and doxycycline on serum interleukin-17 is scarce. We conducted an investigator blinded randomized interventional study to compare the effect of doxycycline, azithromycin and isotretinoin on inflammatory markers and Interleukin-17A (IL-17A) levels in acne. Patients were randomized and received the treatment according to treatment arm till 12 weeks. At baseline and 12 weeks/treatment completion, clinical improvement and Red-cell-distribution width (RDW),Neutrophil-lymphocyte ratio(NLR),Platelet-lymphocyte ratio(PLR), Mean-Platelet volume(MPV), Platelet-distribution width(PDW) and Interleukin-17A levels were analysed. P-value < 0.05 was considered statistically significant. Out of 120 patients, 110 patients completed the study. Baseline Global acne grading scale (GAGS) in doxycycline, azithromycin or isotretinoin group was 24.32 ± 3.119, 24.12 ± 2.804 and 25.10 ± 3.985 respectively and post-treatment was 5.216 ± 1.88, 7.265 ± 2.17 and 2.769 ± 1.08. All the drugs caused a statistically significant decrease in RDW and IL-17A levels. Baseline levels of IL-17A were significantly higher in patients with higher GAGS and post-acne scarring. One of the limitations of our study was that we excluded severe nodulocystic acne patients thereby these results have to be carefully extrapolated.

Three Days of Oral Azithromycin Versus Five Days of Oral Clarithromycin in the Treatment of Campylobacter Enterocolitis in Children: A Prospective Study.

This study aimed to compare the efficacy and tolerability of azithromycin and clarithromycin in pediatric Campylobacter enterocolitis. A prospective, randomized, controlled trial was conducted at a single center. Patients with confirmed Campylobacter enterocolitis were randomly assigned to receive either a 3-day course of azithromycin or a 5-day course of clarithromycin. Symptoms were monitored daily, and changes in laboratory markers (WBC counts, CRP levels, and stool calprotectin) were compared. A total of 29 pediatric patients were included, with 14 patients in the azithromycin group and 15 patients in the clarithromycin group. The median age of patients in the azithromycin group was 10.0 years (interquartile range [IQR]: 5.0-13.0), and in the clarithromycin group, the median age was 9.0 years (IQR: 7.0-13.0) (p = 0.793). The median time to clinical resolution was 3.0 days (IQR: 2.0-3.0) in the azithromycin group and 2.0 days (IQR: 2.0-3.0) in the clarithromycin group (p = 0.132). There were no significant differences in the duration of individual symptoms, including fever, vomiting, and abdominal pain. The length of hospital stay was also similar, with a median stay of 4 days (IQR: 3.0-5.0) in both groups (p = 0.394). Both antibiotics were well-tolerated, with no significant adverse events or treatment discontinuation reported. Clarithromycin was found to be as effective as azithromycin in treating pediatric Campylobacter enterocolitis, with similar clinical outcomes and improvements in laboratory markers.

Compliance with tetracycline eye ointment during annual mass drug administration for trachoma control in the Amhara region, Ethiopia.

A 6-week course of tetracycline eye ointment is an alternative to single -dose oral azithromycin in annual mass drug administration for trachoma control. Compliance with the recommended tetracycline eye ointment regimen has not been well characterised when administered as part of a trachoma control program. A routine mass drug administration for trachoma was carried out in 40 communities in the Amhara region of Ethiopia. Two tubes of tetracycline eye ointment, to be administered twice daily for 6 weeks, was offered to all children under 6 months of age, to pregnant women who declined to take azithromycin, and to all individuals with a macrolide allergy. Seven weeks following the mass drug administration, a treatment compliance survey was performed for all community members documented to have received tetracycline eye ointment during the mass drug administration. Of the 491 individuals documented as having received tetracycline eye ointment from the treatment records, 367 completed the survey, of which 214 recalled being offered tetracycline eye ointment. A total of 105 (49%) respondents reported taking ≥1 daily dose of tetracycline eye ointment on most days of the week for at least the first week. Only 20 (9%) respondents reported taking at least 1 tetracycline eye ointment dose per week for 6 weeks. The most common reasons for low compliance included 'saving it for a future infection' and 'stopped because I (or my child) seemed healthy'. The odds of low compliance were greater for those who reported not having adequate counselling (e.g., odds ratio [OR] 5.3, 95% CI 2.5-28.9 when low compliance was defined as not taking a tetracycline eye ointment dose for most days of at least the first week). Compliance with tetracycline eye ointment was low when administered by a trachoma program during a routine mass drug administration, especially for those reporting inadequate counselling. Further research with a larger sample size and varied settings is warranted to better understand and improve compliance.

Impact of oral azithromycin and intermittent preventive treatment with sulfadoxine-pyrimethamine regimen on child mortality in Sierra Leone: trial protocol for a randomised, two-arm, double-blinded, placebo-controlled clinical trial (ICARIA)

BackgroundAzithromycin has been shown to be beneficial in preventing infectious diseases, including malaria, infectious diarrhoea and pneumonia. A cluster randomised control trial on azithromycin MDA in children in Niger, Malawi and Tanzania found a reduction in all-cause under-five (U5) mortality in communities who received azithromycin compared to placebo. However, the reduction was largest and statistically significant only in Niger. The purpose of this trial is to evaluate the impact of azithromycin plus intermittent preventive treatment in infants (IPTi), recently renamed by the World Health Organisation as perennial malaria chemoprevention (PMC), with sulfadoxine-pyrimethamine (SP) on all-cause mortality up to 18 months of age in children living in areas of high mortality burden through the Expanded Program on Immunisation (EPI) in Sierra Leone.MethodsThe Improving Care through Azithromycin Research for Infants in Africa (ICARIA) trial is a phase III two-arm, individually randomised, double-blinded, placebo-controlled trial administering oral AZI (20 mg/kg bodyweight) at three time points to children attending EPI visits in Sierra Leone. A total of 20,560 infants attending the first EPI contact at around 6 weeks of age are recruited and randomised to AZI or placebo in a 1:1 ratio. The second and third AZI/placebo doses are given at 9 and 15 months of age. The primary outcome of the trial is all-cause mortality rate at 18 months of age assessed through mortality surveillance. Other trial outcomes include the impact on antimicrobial resistance, and on the immune response to certain key routine EPI immunisations, the safety of the intervention, the prevalence of SP resistance markers and the feasibility, and acceptability of adding AZI to the EPI programme.DiscussionThe trial will provide the evidence needed to inform policy regarding the adoption and large-scale implementation of AZI in areas of high-mortality burden in sub-Saharan Africa.Trial registrationClinicalTrials.gov NCT04235816. Registered on 22 January 2020.Pan-African Clinical Trials Registry PACTR202004540256535. Registered on 14 April 2020.

A case of Mycoplasma pneumoniae‐induced rash and mucositis with recent influenza vaccination

AbstractA 33‐year‐old female presented with coryzal symptoms, facial swelling, severe haemorrhagic stomatitis, blistering oral mucositis, conjunctival injection and a sparse targetoid rash on the back and face, requiring admission to hospital. She had received the seasonal influenza vaccination 3 days prior to feeling unwell. Differential diagnosis included erythema multiforme major (EMM) secondary to the influenza vaccine or Mycoplasma pneumoniae‐induced rash and mucositis (MIRM). Oropharyngeal swabs were negative on PCR for cutaneous viruses and Mycoplasma pneumoniae (MP). A skin biopsy from a targetoid lesion on the body showed full thickness epidermal necrosis with epidermal–dermal clefting, numerous civatte bodies and a moderate perivascular infiltrate of lymphocytes and plasma cells in the papillary dermis. She was successfully treated with oral prednisolone and azithromycin. Following discharge from hospital, the paired serological testing for MP returned positive, confirming a diagnosis of MIRM. Our case highlights the difficulties in detecting MP as two diagnostic methods yielded different results, and so we advocate performing both MP PCR and serology to maximise the yield and speed of diagnosis. Secondly, our case highlights the clinical challenge in differentiating MIRM from EMM or Stevens–Johnson syndrome, particularly if there is a potential drug trigger (in our case the influenza vaccine), as all these conditions can feature a severe mucositis with often indistinguishable histological findings. Correct diagnosis of MIRM is important for appropriate and timely administration of anti‐MP antibiotic therapy to facilitate recovery and minimise complications.

Effects of Azithromycin on Blood Inflammatory Gene Expression and Cytokine Production in Sarcoidosis

IntroductionIn sarcoidosis granulomas, monocyte-derived macrophages are activated by pro-inflammatory cytokines including TNF and IL-6. Current drug treatment for sarcoidosis aims to suppress inflammation but disabling side effects can ensue. The macrolide azithromycin may be anti-inflammatory. We aimed to determine whether treatment with azithromycin affects blood inflammatory gene expression and monocyte functions in sarcoidosis.MethodsBlood samples were collected from patients with chronic pulmonary sarcoidosis enrolled in a single arm, open label clinical trial who received oral azithromycin 250 mg once daily for 3 months. Whole blood inflammatory gene expression with or without LPS stimulation was measured using a 770-mRNA panel. Phenotypic analysis and cytokine production were conducted by flow cytometry and ELISA after 24h stimulation with growth factors and TLR ligands. mTOR activity was assessed by measuring phosphorylated S6RP.ResultsDifferential gene expression analysis indicated a state of heightened myeloid cell activation in sarcoidosis. Compared with controls, sarcoidosis patients showed increased LPS responses for several cytokines and chemokines. Treatment with azithromycin had minimal effect on blood gene expression overall, but supervised clustering analysis identified several chemokine genes that were upregulated. At the protein level, azithromycin treatment increased LPS-stimulated TNF and unstimulated IL-8 production. No other cytokines showed significant changes following azithromycin. Blood neutrophil counts fell during azithromycin treatment whereas mononuclear cells remained stable. Azithromycin had no detectable effects on mTOR activity or activation markers.ConclusionBlood myeloid cells are activated in sarcoidosis, but azithromycin therapy did not suppress inflammatory gene expression or cytokine production in blood.Trial registration: EudraCT 2019-000580-24 (17 May 2019)

CLINICAL MANAGEMENT OF CHRONIC ORANGUTAN RESPIRATORY DISEASE SYNDROME IN THREE ADULT MALE BORNEAN ORANGUTANS (PONGO PYGMAEUS).

Orangutan respiratory disease syndrome (ORDS) is a disease unique to orangutans (Pongo sp), characterized by chronic bacterial infection and inflammation of any region or combination of regions of the respiratory tract, including the sinuses, air sacs, cranial bones, airways, and lung parenchyma. Aggressive early intervention during a first episode may prevent progression to chronic disease. However, in the setting of an established chronic disease, intermittent acute exacerbations are associated with worsening symptoms and increased infection and inflammation. ORDS is ultimately fatal due to loss of respiratory function resulting from chronic structural damage. Utilizing potentially lifelong medications to slow the progression of chronic, destructive inflammation in the respiratory tract, chronic treatment is aimed at stabilizing the animals' respiratory function, decreasing the frequency of recurrent exacerbations, and improving their general well-being. Three adult male Bornean orangutans (Pongo pygmaeus) housed at an orangutan rehabilitation and reintroduction center in Indonesia have long histories of recurrent respiratory disease. Each underwent CT scans confirming ORDS with chronic airway disease prior to initiation of a long-term treatment protocol. Based on data-driven medical management of bronchiectasis in humans, the three orangutans have been treated with long-term combination regimens of oral azithromycin, nebulized salbutamol, and nebulized hypertonic saline. Follow-up CT scans in all three animals at least 1 yr following treatment initiation showed improvements throughout their respiratory tracts. The duration of each exacerbation period decreased, and the orangutans have longer symptom-free periods compared to before the start of treatment. At an average of 5 yr into the long-term treatment protocol, all three orangutans are thriving. Chronic medical management of ORDS modeled after human treatment of bronchiectasis has been efficacious in these three orangutans and encourages further study of this approach.

Analysis of the Efficacy of Erythromycin Cyclic 11,12-Carbonate Combined with Azithromycin in the Treatment of Severe Mycoplasma Pneumoniae Pneumonia in Children and its Effect on Cytokines

Introduction: Mycoplasma Pneumoniae Pneumonia (MPP) is an inflammation of the lungs caused by Mycoplasma pneumoniae infection. Macrolide antibiotics are the therapeutic agents of choice for MPP. This study aimed to explore the efficacy of erythromycin cyclic 11,12-carbonate combined with azithromycin in treating children with severe Mycoplasma pneumoniae pneumonia (SMPP). Methods: 84 children with SMPP treated at Hubei Maternal and Child Health Hospital between February 2021 and December 2021 were randomly divided into two groups. The control group was treated with intravenous azithromycin and then changed to oral azithromycin. The experimental group was treated with intravenous azithromycin and then switched to oral erythromycin cyclic 11,12-carbonate. The clinical efficacy, symptom improvement, inflammatory levels, and cytokine levels before and after treatment were compared, and the occurrence of adverse reactions was recorded. Results: The overall effective rate of treatment in the experimental group was significantly higher than that in the control group (P&lt;0.05). The time to the disappearance of clinical symptoms and length of hospitalization of the experimental group was significantly shorter than that of the control group (P&lt;0.05). After treatment, inflammatory levels and cytokine levels of the experimental group were significantly lower than those of the control group (P&lt;0.05). There was no difference in the incidence of adverse reactions between the two groups (P&gt;0.05). Conclusion: Erythromycin cyclic 11,12-carbonate combined with azithromycin in the treatment of children with SMPP had significant efficacy, superior to azithromycin monotherapy, which could effectively improve immune function and clinical symptoms.

Effectiveness of Oral Azithromycin in Treating Enteric Fever: A Hospital-Based Study on Pediatric Patients.

Introduction Enteric fever is prevalent in underdeveloped and developing countries. It is caused by Salmonella Typhi, which has developed resistance over the years to commonly used antimicrobials. Meropenem is an effective treatment for all complicated and uncomplicated extensively drug-resistant (XDR) bacteria, but it is administered intravenously, three times daily, by infusion, and it is quite expensive for the patient. Oral azithromycin is shown by some authors to be effective in extensively drug-resistant enteric fever. Material and methods This retrospective cross-sectional study was conducted in the outpatient department of Lady Reading HospitalMedical Teaching Institution, Peshawar. The duration of the study was one year. Data was collected after approval from the hospital's Ethical and Research Committee. All pediatric patients meeting the inclusion criteria for extensively drug-resistant enteric fever were included. Data on patient demographics, blood culture and laboratory results, treatment given, and effectiveness were documented in a specialized proforma. Statistical Package for Social Sciences (SPSS) version 23 (IBM Corp., Armonk, NY, US) was used for data analysis. Results Out of the total 106 patients, 72 (67.9%) were male and 34 (32.1%) were female. The mean age was 7.51 ± 2.75 years, with a range of 1 to 15 years. Among them, 66 (62.3%) had anemia (hemoglobin less than 11grams per deciliter for under 5 years and 11.5 for 5-15 years old children), with a mean hemoglobin level of 10.6 ± 1.53 grams per deciliter (g/dl), ranging from 7.2 to 13.8 g/dl. Thrombocytopenia was found in 14 (13%) patients. The mean platelet count was 317 x 103 ± 164 cells per microliter, with a range of 61 x 103 to 834 x 103cells per liter. The mean total leukocyte count was 9.71x 103 ± 4.321 cells per microliter, with a range of 2.01 x 103 to 30.40 x103cells per microliter. However, leucopenia was seen in only 5 (4.7%) patients. In 98.1% of cases, azithromycin was found to be effective in treating enteric fever caused by extensively drug-resistant Salmonella. Conclusion Azithromycin is effective in treating extensively drug-resistant enteric fever. It can be confidently used in patients with no or mild complications with extensively drug-resistant enteric fever. Good compliance and complete dosage should be followed to avoid resistance to this drug. Blood cultures should always be sent when prescribing antibiotics, especially when suspecting enteric fever.

Difficult diagnosis: Disseminated gonorrheal infection manifesting as septic arthritis.

Disseminated gonococcal infection is the causative agent of approximately 0.6%-1.2% of septic arthritis cases in North America and Europe. Typical presentations of this disorder include tenosynovitis, dermatitis, polyarthralgia, or oligoarticular purulent arthritis affecting the distal joints. Diagnosis is contingent on clinical presentation, with urine nucleic acid amplification testing as the preferred diagnostic modality. Synovial fluid cultures, along with imaging, can confirm diagnosis. The recommended treatment is a third-generation cephalosporin, such as intravenous ceftriaxone for 7-14 days and a dose of oral azithromycin.

Increased risk of pigmentary degeneration of the iris and pigmentary glaucoma with fluoroquinolone antibiotics.

Fluoroquinolones are popular antibiotics used for a myriad of conditions including ocular procedures. Despite numerous case reports of acute pigmentary degeneration of the iris with fluoroquinolone use, a pharmacoepidemiological study has not been performed to examine and quantify this risk. Retrospective cohort study with a case-control analysis. A cohort of 1,231,881 new users of oral or topical moxifloxacin, levofloxacin, and azithromycin were followed to first diagnosis of pigmentary degeneration of the iris or pigmentary glaucoma. Four controls were selected for each case using density sampling, matching on age and calendar time. Users of oral or topical moxifloxacin were compared to levofloxacin and azithromycin, a negative control drug from a separate class. First incidence of pigmentary degeneration of the iris or pigmentary glaucoma. The cohort was comprised of 1,231,881 new users of topical or oral levofloxacin, moxifloxacin, or azithromycin. 542 cases of pigmentary degeneration of the iris and 460 cases of pigmentary glaucoma were identified. The incidence of iris pigmentary degeneration or pigmentary glaucoma for topical moxifloxacin was 10.2/1000 person years compared to 2.6/1000 person years for topical azithromycin. Current topical moxifloxacin users had the highest adjusted IRR for pigmentary degeneration of the iris (IRR = 6.81, [95%CI:2.00-23.18]) and pigmentary glaucoma (IRR = 4.07 [95%CI:1.42-11.62]) respectively. The study findings suggest that patients using topical moxifloxacin may have increased risk of developing pigmentary degeneration of the iris and pigmentary glaucoma although the absolute increase was low. Future studies are needed to confirm this association.

Unmasking Acne: Azithromycin Edges Out Doxycycline in Randomized Trial at Tertiary Care Centre

Background: Acne vulgaris, a prevalent global condition, often necessitates antibiotic therapy. Doxycycline has been a mainstay treatment; however, recent research suggests azithromycin might be superior. Conflicting data and a lack of local studies regarding their comparative efficacy warrant further investigation. Objectives: This study aimed to compare the efficacy of oral azithromycin with oral doxycycline in treating acne vulgaris at a tertiary care hospital in Islamabad. Methods: A randomized controlled trial was conducted. Patients aged 14-30 years (n=190) were enrolled and randomly assigned to either azithromycin or doxycycline treatment groups. Baseline and post-treatment (12 weeks) Global Acne Grading System (GAGS) scores were assessed. Percent reductions in GAGS score were categorized into four groups (&lt;25%, 25-50%, 51-75%, and &gt;75%) for intergroup comparison. Written informed consent was obtained from all participants. Results: The mean patient age was 21.30±4.93 years, with a female predominance (male:female ratio 1:1.2). Most patients had Fitz-Patrick Skin Type-V (64.7%) compared to Type-IV (35.3%). Baseline GAGS scores were comparable between groups (p=0.612). Notably, post-treatment GAGS scores were significantly lower in the azithromycin group (p&lt;0.001), demonstrated by a greater mean change (19.33±3.03 vs. 17.70±2.99; p&lt;0.001) and percent reduction (81.87±8.74 vs. 75.97±11.12%; p&lt;0.001) compared to doxycycline. Additionally, 75.3% of patients achieved an excellent reduction in GAGS score, with a significantly higher proportion observed in the azithromycin group (87.4% vs. 63.2%; p&lt;0.001). Similar significant differences were observed across subgroups based on age, gender, and skin type. Conclusion: This study suggests that azithromycin demonstrates superior efficacy to doxycycline for acne vulgaris management, regardless of patient demographics or skin type. Its established better safety profile further supports its potential as a preferred therapeutic option in future dermatological practice. Keywords: Acne Vulgaris, Azithromycin, Doxycycline, Percent Reduction in GAGS Score

Azithromycin dosing and preterm premature rupture of membranes treatment (ADAPT): a randomized controlled Phase I trial

BackgroundSeven days of antibiotics are recommended in the setting of preterm premature rupture of membranes (PPROM) to promote latency. Azithromycin has generally replaced a seven-day course of erythromycin in current clinical practice. Azithromycin clears from plasma quickly and concentrates in local tissue which is why daily dosing is not always needed and local tissue, rather than plasma, concentrations are used to determine dosing. Based on limited pharmacokinetic studies in pregnancy, 1g one time dose of azithromycin may not maintain local (amniotic fluid) drug concentrations above minimum inhibitory concentrations (MIC50) for common genitourinary pathogens (50-500ng/ml). ObjectiveWe aim to compare the pharmacokinetics of one-time vs daily dosing of azithromycin in the setting of preterm pre-labor rupture of membranes (PPROM) Study DesignThis is a randomized clinical trial of singletons with PPROM randomized to 1gram oral azithromycin once or 500mg oral azithromycin daily x7 days. Primary outcome was amniotic fluid azithromycin concentrations over 8 days. Secondary outcomes included plasma azithromycin trough concentrations. Plasma was collected at time points 1-4hrs and 12-24hrs after first dose, and then every 24hrs through 8 days. Amniotic fluid was collected opportunistically throughout the day noninvasively with Always Flex-foam pads. We aimed to enroll 20 participants to achieve N=5 still pregnant through 8 days in each group. Continuous variables compared with Mann Whitney U test and relationship between azithromycin concentration and time assessed with linear regression. ResultsThe study was halted after N=6 enrolled due to lagging enrollment, with 3 in each group. The mean gestational age of enrollment was 27.1±1.7weeks in the 1g group and 31.0±1.4 weeks in the 500mg daily group. One participant in each group had latency to delivery >7days. Regarding amniotic fluid azithromycin concentration, there was a difference in change in amniotic fluid azithromycin concentration over time between groups (p<0.001). Amniotic fluid concentration of azithromycin was relatively stable in the 1g once group (B=-0.07 (-0.44 – 0.31), p=0.71), in contrast, amniotic fluid concentration (ng/ml) increased over time (hours) in the 500mg daily group (B=1.3 (0.7 – 1.9), p<0.001). By ≥96hours median amniotic fluid levels of azithromycin were lower in the 1g once dosing group (median 11[7-56]) compared to 500mg daily (median 46 [23-196]), with a median difference -27 (-154 to -1), p=0.03. In plasma, there was higher azithromycin concentration during the first 24hrs with 1g once vs 500mg daily (median difference 637ng/ml (101-1547), p=0.01), however by ≥96hrs plasma azithromycin declined and was virtually undetectable in the 1g once group, while trough plasma levels in the 500mg remained elevated (median difference -207ng/ml (-271 to -155), p=0.03). Conclusion500mg daily dosing of azithromycin maintains higher amniotic fluid concentrations, and more consistently greater than common MICs, over eight days compared to 1g once in the setting of PPROM.

Sequential development of diffuse panbronchiolitis and myasthenia gravis after thymectomy for thymic neoplasm: a case report

BackgroundMyasthenia gravis (MG) is the most common paraneoplastic disorder associated with thymic neoplasms. MG can develop after thymectomy, and this condition is referred to post-thymectomy myasthenia gravis (PTMG). Diffuse panbronchiolitis (DPB), is a rare form of bronchiolitis and is largely restricted to East Asia, has been reported in association with thymic neoplasms. Only three cases of combined MG and DPB have been reported in the literature.Case presentationA 45-year-old Taiwanese woman presented to our hospital with productive cough, rhinorrhea, anosmia, ear fullness, shortness of breath, and weight loss. She had a history of thymoma, and she underwent thymectomy with adjuvant radiotherapy 7 years ago. Chest computed tomography scan revealed diffuse bronchitis and bronchiolitis. DPB was confirmed after video-assisted thoracoscopic surgery lung biopsy, and repeated sputum cultures grew Pseudomonas aeruginosa. She has been on long-term oral azithromycin therapy thereafter. Intravenous antipseudomonal antibiotics, inhaled amikacin, as well as oral levofloxacin were administered. Three months after DPB diagnosis, she developed ptosis, muscle weakness, and hypercapnia requiring the use of noninvasive positive pressure ventilation. MG was diagnosed based on the acetylcholine receptor antibody and repetitive stimulation test results. Her muscle weakness gradually improved after pyridostigmine and corticosteroid therapies. Oral corticosteroids could be tapered off ten months after the diagnosis of MG. She is currently maintained on azithromycin, pyridostigmine, and inhaled amikacin therapies, with intravenous antibiotics administered occasionally during hospitalizations for respiratory infections.ConclusionsTo our knowledge, this might be the first case report of sequential development of DPB followed by PTMG. The coexistence of these two disorders poses a therapeutic challenge for balancing infection control for DPB and immunosuppressant therapies for MG.

Long-term, Low-Dose Oral Azithromycin Treatment for Chronic Severe Bilateral Blepharokeratoconjunctivitis in Pediatric Patients.

To evaluate the efficacy and safety of oral azithromycin treatment combined with topical antibiotic and anti-inflammatory agents in pediatric patients with chronic severe bilateral blepharokeratoconjunctivitis. Patients younger than 14 years with chronic and severe bilateral blepharokeratoconjunctivitis were reviewed retrospectively. Consecutive patients receiving oral azithromycin treatment were included. All patients received oral azithromycin (5 mg/kg/single dose daily) for at least 4 weeks combined with topical antibiotic and anti-inflammatory agents. Before and after the treatment, clinical symptoms were noted, and corneal and conjunctival fluorescein staining and corneal neovascularization were graded. Meibomian gland secretion and meibomian gland plugging were also assessed. All patients completed at least 3 months of follow-up after completion of the oral azithromycin treatment. Patients' clinical data at the time of diagnosis and last follow-up visit were statistically compared. Twenty-nine children (58 eyes, mean age of 6.51 years) were included. The mean time of oral azithromycin use was 5.87 weeks (range: 4 to 10 weeks). Clinical symptoms and signs and visual acuity were significantly improved after treatment. The mean fluorescein staining and corneal neovascularization grades and meibomian gland secretion and meibomian gland plugging scores also improved after treatment (P < .001). Eyelid distortion or fornix shortening was not observed. At the last follow-up visit, all patients were stable with treatment only with daily eyelid hygiene, topical cyclosporine, and artificial tears. Long-term, low-dose oral azithromycin combined with topical antibiotic and anti-inflammatory agents is an effective treatment option for pediatric patients with chronic severe bilateral blepharokeratoconjunctivitis. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XX-XX.].

Compliance With CDC-Recommended 7-Day Chlamydia Treatment in Nonpregnant Adult Female Patients in Low-Resource Communities: 1-Year Data [ID 2683472

INTRODUCTION: In 2021, the Centers for Disease Control and Prevention (CDC) changed treatment guidelines for chlamydia (Chlamydia trachomatis) infections in nonpregnant women, as substantial data demonstrated oral doxycycline at 100 mg twice daily for 7 days as superior to one-dose oral azithromycin at 1 g. Previously, the two antibiotic regimens were considered equivocal, allowing providers to opt for the shorter regimen course to optimize compliance and cure rate. METHODS: We assessed the compliance rate of patients in low-resource communities to the multidose doxycycline regimen via retrospective chart review. For a 12-month period, all nonpregnant adult female patients prescribed doxycycline for chlamydia infection at a county hospital system were included in the IRB-exempt study. Patients were called 7–10 days after initial doxycycline prescription to assess compliance, medication side effects, and adherence barriers. Noncompliant patients were offered a prescription for the azithromycin regimen. Patients were encouraged to repeat chlamydia testing in 4 weeks to assess for cure, or in 3 months for reinfection. RESULTS: Two hundred sixty-four patients met inclusion criteria, 193 (73.1%) of whom could be contacted. Patients were significantly compliant to multidose doxycycline despite barriers (P=.0002; 95% CI, 3.33–50.48), such as pharmacy-induced medication fill delay and medication side effects. Only 7 (58.3%) noncompliant patients desired to switch to azithromycin. Of the 105 compliant patients re-tested, most (87.6%) tested negative. CONCLUSION: The data demonstrated that patients in low-resource communities are significantly compliant with the CDC-recommended 7-day doxycycline regimen despite barriers to adherence. Therefore, even in low-resource communities, practitioners should prescribe multidose doxycycline for chlamydia infection in nonpregnant females.

Single-Dose Azithromycin Prophylaxis in Planned Vaginal Delivery for Sepsis Prevention: A Systematic Review and Meta-analysis of Randomized Controlled Trials [ID 2683483

INTRODUCTION: The use of oral azithromycin as a preventive measure against postpartum infections of planned vaginal births has been the subject of many randomized controlled trials. However, the results from these trials have not been consistent. Therefore, performed a systematic review and meta-analysis to determine whether the use of a single-dose of oral azithromycin is clinically significant. METHODS: We systematically searched PubMed, Embase and Cochrane Central for RCTs from May to June 2023, comparing a single dose of oral azithromycin to placebo in patients undergoing planned vaginal delivery at minimum 28 weeks of gestational age. The main outcomes were puerperal and neonatal sepsis. Statistical analyses were performed using Review Manager 5.4.1 (Cochrane Collaboration). Heterogeneity was assessed with I2 statistics. RESULTS: Four randomized controlled trials were included (mothers, n= 42,235; newborns n= 42,492). Approximately 49.8% of mothers received a single dose of oral azithromycin for sepsis prophylaxis. Azithromycin significantly reduced the incidence of puerperal sepsis (risk ratio [RR] 0.65; 95% CI; P&lt;.001), mastitis or breast abscess (RR 0.58; 95% CI; P&lt;.001), endometritis (RR 0.65; 95% CI; P&lt;.001), wound infection (RR 0.81; 95% CI; P=.013), infection rate (RR 0.62; 95% CI; P&lt;.001) and fever (RR 0.50; 95% CI, 0.28–0.89; P=.018) in mothers compared to placebo. CONCLUSION: Azithromycin shows to be an effective preventive measure against many postpartum infections in mothers but a substantial effect on neonatal outcomes has not yet been conclusively observed.