Subject(s)
Bronchodilator Agents , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/diagnosis , Bronchodilator Agents/therapeutic use , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/adverse effectsABSTRACT
The present investigation aimed to quantitatively assess the level of parasitemia in dogs using qPCR.The dogs selected for this study were infected with the haemoprotozoan parasite Babesia gibsoni. In the study, dogs diagnosed with babesiosis were divided into two groups (n = 12) and subjected to distinct treatment strategies. The first group received clindamycin-metronidazole-doxycycline (CMD) therapy, while the second group was treated with a combination of buparvaquone-azithromycin (BPV-AZM). The level of parasitemia in the infected dogs was determined using an absolute quantification-based qPCR method. This assessment was conducted both prior to initiating the treatment and on the 10th day following the commencement of the treatment protocols. On the tenth day after the initiation of treatment, the CMD group exhibited a lower level of parasitemia in comparison to the BPV-AZM group. In the CMD treated groups, the mean parasitemia decreased from 4.9E + 06 to 3.4E + 06, indicating a reduction in parasitic load. Conversely, in the BPV-AZM treatment groups, the mean parasitemia increased from 1.62E + 06 to 2.87E + 06, suggesting an increase in parasitic load. On the 10th day, the CMD-treated group demonstrated a statistically significant decline in the level of parasitemia, with a P-value of ≤0.001. This indicates a strong and significant reduction in parasitic load following the CMD treatment. Therefore, the absolute quantification-based qPCR method could effectively assess the initial treatment response by measuring the level of parasitemia.
Subject(s)
Babesia , Babesiosis , Clindamycin , Dog Diseases , Parasite Load , Parasitemia , Real-Time Polymerase Chain Reaction , Animals , Dogs , Dog Diseases/parasitology , Dog Diseases/diagnosis , Dog Diseases/drug therapy , Real-Time Polymerase Chain Reaction/methods , Babesia/genetics , Babesia/isolation & purification , Parasitemia/parasitology , Parasitemia/veterinary , Babesiosis/parasitology , Babesiosis/diagnosis , Clindamycin/therapeutic use , Parasite Load/methods , Doxycycline/therapeutic use , Azithromycin/therapeutic use , Metronidazole/therapeutic use , Antiprotozoal Agents/therapeutic use , NaphthoquinonesABSTRACT
OBJECTIVES: While Mycoplasma genitalium is reported as a common rectal infection among men who have sex with men (MSM), published data refer predominantly to urethral infections. Currently, most guidelines recommend M. genitalium testing from urine in men with symptomatic, non-gonococcal urethritis. Macrolide resistance-associated mutations (MRMs) among M. genitalium have increased during the last decade especially among MSM. We aim to demonstrate the prevalence and anatomical distribution of M. genitalium infection and MRM in urine and rectal specimens among MSM in Sweden. METHODS: In this cross-sectional study in 2019, paired urine and rectal samples from symptomatic and asymptomatic MSM attending a sexually transmitted infection clinic in the south of Sweden were screened for M. genitalium, presence of MRM, Neisseria gonorrhoeae, Chlamydia trachomatis, HIV and syphilis. RESULTS: The overall prevalence of M. genitalium was 10.5% (64 of 609), rectal samples 7.6% (46 of 609) and urine samples 3.9% (24 of 609) (p=0.007). Among M. genitalium-positive cases, single rectal and single urethral infection was detected in 62.5% (40 of 64) and 28.1% (18 of 64), respectively (p<0.0001). Infection at both sites was seen in 9.4% (6 of 64). The prevalence of MRM was 67.9% (19 of 28). M. genitalium was significantly associated with HIV (OR 2.60, 95% CI 1.14 to 5.88, p=0.02). Among the MSM, 7.4% (45 of 609) were infected with N. gonorrhoeae, 6.7% (41 of 609) with C. trachomatis, 7.1% (43 of 609) with HIV and 0.7% (4 of 609) with syphilis. CONCLUSIONS: In this study, among MSM, most infections with M. genitalium were detected as rectal mono infections. The prevalence of M. genitalium among MSM was almost twofold higher in rectal samples (7.6%) compared with urine samples (3.9%). The prevalence of macrolide resistance was high with no difference between urine and rectal samples.
ABSTRACT
OBJECTIVES: . The United States Centers for Disease Control and Prevention (CDC) conducts active surveillance for typhoid fever cases caused by Salmonella enterica serovar Typhi (Typhi). Here we describe the characteristics of the first two cases of mph(A)-positive azithromycin-resistant Typhi identified through US surveillance. METHODS: . Isolates were submitted to public health laboratories, sequenced, and screened for antimicrobial resistance determinants and plasmids, as part of CDC PulseNet's routine genomic surveillance. Antimicrobial susceptibility testing and long-read sequencing were also performed. Basic case information (age, sex, travel, outcome) was collected through routine questionnaires; additional epidemiological data was requested through follow-up patient interviews. RESULTS: . The patients are related and both reported travel to India (overlapping travel dates) before illness onset. Both Typhi genomes belong to the GenoTyphi lineage 4.3.1.1 and carry the azithromycin-resistance gene mph(A) on a PTU-FE (IncFIA/FIB/FII) plasmid. These strains differ genetically from mph(A)-positive Typhi genomes recently reported from Pakistan, suggesting independent emergence of azithromycin resistance in India. CONCLUSIONS: . Cases of typhoid fever caused by Typhi strains resistant to all available oral treatment options are cause for concern and support the need for vaccination of travelers to Typhi endemic regions. US genomic surveillance serves as an important global sentinel for detection of strains with known and emerging antimicrobial resistance profiles, including strains from areas where routine surveillance is not conducted.
Subject(s)
Bronchodilator Agents , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/diagnosis , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/therapeutic use , Bronchodilator Agents/adverse effects , Administration, InhalationABSTRACT
BACKGROUND: Sepsis is a syndrome that occurs following an infection and marked by severe inflammatory responses, and if not treated in time, it can lead to multi-organ failure syndrome and death. This study examines the effects of a novel combination therapy using azithromycin and mesenchymal stem cell-derived extracellular vesicles (EVs) on a cecal ligation and puncture (CLP) model of sepsis. METHODS: Human Wharton's jelly-mesenchymal stem cells were cultured, characterized, and used to extract EVs. The CLP sepsis model was induced in mice, followed by treatments: saline, AZM, EVs, and combination therapy (A+E). Clinical sepsis scores were recorded 24 h post-treatment. Serum, peritoneal fluid, and organ tissues (kidney, liver, lung) were collected and analyzed for biochemical parameters (AST ALT, and creatinine), inflammatory markers, bacterial load, and histopathological changes. RESULTS: The A+E combined treatment improved the clinical scores of septic mice. The administration of A+E reduced bacterial loads in the peritoneum of septic mice, contributing to effective control of infection. Inflammatory markers of neutrophils-to-lymphocytes ratio (NLR) and TNF-α serum levels were significantly lower in the combinational therapy group, indicating significant anti-inflammatory effect of this combination. Additionally, combination of AZM and EVs alleviated organ damage mainly within liver, kidneys and lungs. Based on histopathological assessments and biochemical parameters, there was diminished tissue damage as well as reduced inflammation, which is correlated with improved functions of these vital organs. CONCLUSION: The combined use of azithromycin and EVs offers a promising therapeutic approach for sepsis by effectively controlling infection and modulating the inflammatory response.
Subject(s)
Azithromycin , Disease Models, Animal , Extracellular Vesicles , Mesenchymal Stem Cells , Sepsis , Animals , Azithromycin/therapeutic use , Azithromycin/pharmacology , Sepsis/drug therapy , Sepsis/therapy , Humans , Mice , Male , Anti-Bacterial Agents/therapeutic use , Cecum/surgery , Ligation , Mesenchymal Stem Cell Transplantation , Cells, CulturedABSTRACT
Since 2022, Europe has had 4 cases of extensively drug-resistant Neisseria gonorrhoeae, sequence type 16406, that is resistant to ceftriaxone and highly resistant to azithromycin. We report 2 new cases from France in 2023 involving strains genetically related to the 4 cases from Europe as well as isolates from Cambodia.
Subject(s)
Anti-Bacterial Agents , Drug Resistance, Multiple, Bacterial , Gonorrhea , Neisseria gonorrhoeae , Neisseria gonorrhoeae/drug effects , Neisseria gonorrhoeae/genetics , Neisseria gonorrhoeae/isolation & purification , Humans , Gonorrhea/drug therapy , Gonorrhea/microbiology , Gonorrhea/epidemiology , France/epidemiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Male , Drug Resistance, Multiple, Bacterial/genetics , Microbial Sensitivity Tests , Adult , Female , Azithromycin/pharmacology , Azithromycin/therapeutic use , Ceftriaxone/pharmacology , Ceftriaxone/therapeutic useABSTRACT
Background and Aim: The importance of monitoring antimicrobial residues in food is underlined by increasing worries about food safety and public health. The potential toxicity of azithromycin (Az) on broilers and its impact on chicken meat residues require further investigation. This study assesses Az's toxicity effects and associated risks in broiler chickens through evaluation. Materials and Methods: One hundred and twenty chicks were distributed into four equal groups randomly. Each group received different daily oral doses of Az: 200 mg/kg for Az1, 100 mg/kg for Az2, and 50 mg/kg for Az3. The FAz group was given plain water. High-performance liquid chromatography was used to measure Az residue levels in muscle and liver. Oxidative markers (malondialdehyde [MDA], superoxide dismutase [SOD], catalase [CAT]), liver and kidney function tests, and histopathological examination were conducted. Results: The levels of alanine aminotransferase and aspartate aminotransferase increased in Az1 and Az2 groups from 8 h to 3 days and decreased slightly in Az2 by 7 days, while they remained normal in Az3. The levels of uric acid and creatine in the Az1 and Az2 groups increased from 8 h to 3 days and subsequently decreased in Az2 by the 7th day. Az1 group showed the highest increase in MDA levels within 7 days. With higher Az doses, SOD and CAT levels showed a more significant decrease post-treatment. 9.1 µg/kg Az1 liver had the highest residues, whereas none were detected in muscle. Conclusion: At higher doses, Az caused significant liver and kidney damage, whereas lower doses had negligible effects. Muscle tissue contains fewer Az residues than liver. Assessing risks and ensuring compliance with regulations necessitate constant surveillance of Az residues in food. The health implications and risk management insights necessitate further investigation into the long-term effects of Az residues.
ABSTRACT
BACKGROUND: Macrolide antibiotics, including azithromycin, can reduce under 5 years of age mortality rates and treat various infections in children in sub-Saharan Africa. These exposures, however, can select for antibiotic-resistant bacteria in the gut microbiota. METHODS: Our previous randomized controlled trial (RCT) of a rapid-test-and-treat strategy for severe acute diarrheal disease in children in Botswana included an intervention (3-day azithromycin dose) group and a control group that received supportive treatment. In this prospective matched cohort study using stools collected at baseline and 60 days after treatment from RCT participants, the collection of antibiotic resistance genes or resistome was compared between groups. RESULTS: Certain macrolide resistance genes increased in prevalence by 13%-55% at 60 days, without differences in gene presence between the intervention and control groups. These genes were linked to tetracycline resistance genes and mobile genetic elements. CONCLUSIONS: Azithromycin treatment for bacterial diarrhea for young children in Botswana resulted in similar effects on the gut resistome as the supportive treatment and did not provide additional selective pressure for macrolide resistance gene maintenance. The gut microbiota of these children contains diverse macrolide resistance genes that may be transferred within the gut upon repeated exposures to azithromycin or coselected by other antibiotics. CLINICAL TRIALS REGISTRATION: NCT02803827.
Subject(s)
Anti-Bacterial Agents , Azithromycin , Diarrhea , Gastrointestinal Microbiome , Humans , Azithromycin/therapeutic use , Azithromycin/administration & dosage , Botswana , Diarrhea/microbiology , Diarrhea/drug therapy , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Child, Preschool , Infant , Prospective Studies , Female , Male , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/genetics , Drug Resistance, Bacterial/genetics , Feces/microbiology , Bacteria/drug effects , Bacteria/genetics , Bacteria/classification , Bacteria/isolation & purificationABSTRACT
BACKGROUND: Chronic lung disease (CLD) is common among children with HIV (CWH) including in those taking antiretroviral therapy (ART). Azithromycin has both antimicrobial and anti-inflammatory effects and has been effective in improving lung function in a variety of lung diseases. We investigated lung function trajectories among CWH with CLD on ART enrolled in a randomized controlled trial of adjuvant azithromycin. We also investigated factors that modified the effect of azithromycin on lung function. METHODS: The study used data from a double-blinded placebo-controlled trial conducted in Malawi and Zimbabwe of 48 weeks on azithromycin (BREATHE: ClinicalTrials.gov NCT02426112) among CWH aged 6 to 19 years taking ART for at least six months who had a forced expiratory volume in one second (FEV1) z-score <-1.0. Participants had a further follow-up period of 24 weeks after intervention cessation. FEV1, forced vital capacity (FVC) and FEV1/FVC were measured at baseline, 24, 48 and 72-weeks and z-scores values calculated. Generalized estimating equations (GEE) models were used to determine the mean effect of azithromycin on lung-function z-scores at each follow-up time point. RESULTS: Overall, 347 adolescents (51% male, median age 15 years) were randomized to azithromycin or placebo. The median duration on ART was 6.2 (interquartile range: 3.8-8.6) years and 56.2% had an HIV viral load < 1000copies/ml at baseline. At baseline, the mean FEV1 z-score was - 2.0 (0.7) with 44.7% (n = 155) having an FEV1 z-score <-2, and 10.1% had microbiological evidence of azithromycin resistance. In both trial arms, FEV1 and FVC z-scores improved by 24 weeks but appeared to decline thereafter. The adjusted overall mean difference in FEV1 z-score between the azithromycin and placebo arms was 0.004 [-0.08, 0.09] suggesting no azithromycin effect and this was similar for other lung function parameters. There was no evidence of interaction between azithromycin effect and baseline age, lung function, azithromycin resistance or HIV viral load. CONCLUSION: There was no observed azithromycin effect on lung function z-scores at any time point suggesting no therapeutic effect on lung function. TRIAL REGISTRATION: ClinicalTrials.gov NCT02426112. First registered on 24/04/2015.
Subject(s)
Azithromycin , HIV Infections , Lung Diseases , Humans , Azithromycin/therapeutic use , HIV Infections/drug therapy , HIV Infections/complications , Male , Adolescent , Female , Child , Double-Blind Method , Forced Expiratory Volume/drug effects , Chronic Disease , Vital Capacity , Lung Diseases/drug therapy , Lung Diseases/physiopathology , Anti-Bacterial Agents/therapeutic use , Young Adult , Malawi , Lung/physiopathology , Lung/drug effects , Zimbabwe , Respiratory Function Tests , Longitudinal StudiesABSTRACT
PURPOSE: In the early stages of the COVID-19 pandemic, preliminary results that later proved to be incorrect suggested the possible efficacy of anti-infective drugs such as azithromycin for the treatment of SARS-CoV-2 infection. These preliminary data may have influenced the prescription of azithromycin. However, no individual-level data linking the use of this antibiotic to acute SARS-CoV-2 infection are available. The present analysis aims to fill this gap. METHODS: A retrospective population-based cohort design was used including patients diagnosed with SARS-CoV-2 infection in the period ranging from February 2020 to February 2022. The data source for antibiotic consumption was the drug database of outpatient prescriptions of Emilia-Romagna Region (Italy). Antibiotics were classified according to the Anatomical Therapeutic Chemical (ATC) classification system. Consumption rates and percentages of azithromycin DDDs (defined daily doses) during the acute phase of the infection were compared with a previous control period and with the post-acute phase. Analyses were stratified by four groups according to the prevalent virus variant at time of diagnosis. RESULTS: Comparing the previous control period with the acute phase of infections, the rates of azithromycin consumption (DDD per 1000 individuals per day) increased from 1.17 to 23.11, from 0.80 to 33.03, from 0.81 to 21.01, and from 1.02 to 9.76, in the pre-Alpha, Alpha, Delta, and Omicron periods, respectively. Similarly, the percentages of individuals receiving azithromycin, and the azithromycin DDDs percentages over total systemic antibiotics DDDs increased in acute phases of infection compared with control periods. The consumption rates and percentages returned to preinfection levels in the post-acute phase. In the study period, 12.9% of the use of azithromycin in the entire adult population of Emilia-Romagna was attributable to acute SARS-CoV-2 infection. CONCLUSIONS: Considering the low likelihood of bacterial coinfections, the increased azithromycin consumption in the acute phase of SARS-CoV-2 infection suggests inappropriate prescribing of this antibiotic.
Subject(s)
Anti-Bacterial Agents , Azithromycin , COVID-19 Drug Treatment , COVID-19 , Azithromycin/therapeutic use , Humans , Retrospective Studies , Female , Male , Middle Aged , Anti-Bacterial Agents/therapeutic use , Italy/epidemiology , Aged , Adult , COVID-19/epidemiology , SARS-CoV-2 , Young Adult , Aged, 80 and over , Adolescent , Acute Disease , Practice Patterns, Physicians'/statistics & numerical data , Cohort StudiesABSTRACT
INTRODUCTION: Azithromycin is an effective treatment for various respiratory conditions but its effect on cough is poorly understood. We synthesised data from randomised controlled trials (RCTs) and noncomparative studies (NCT) examining its effect on objective and subjective cough. METHODS: After prospective registration on PROSPERO, we searched MEDLINE, EMBASE, and CENTRAL for both RCTs and NCT trials examining the effect azithromycin on cough in respiratory disease. RESULTS: We identified 1240 studies of which 6 (4 RCTs and 2 NCT studies) were included in the meta-analysis, with a total of 275 patients. Azithromycin was associated with significant improvement in Leicester Cough Questionnaire scores at follow-up when compared to baseline scores (SMD = 0.62 [95% CI 0.12 to 1.12], p = 0.01). However, when only RCTs were synthesised, no significant effect was observed (SMD = 0.12 [95% CI - 0.36 to 0.60], p = 0.62). There was no significant reduction in cough severity VAS score (SMD = - 0.39 [95% CI - 0.92 to 0.14], p = 0.15). There was no significant reduction in objective cough count (SMD = - 0.41 [95% CI - 1.04 to 0.32], p = 0.09). CONCLUSION: Azithromycin therapy improves cough-related quality of life in various chronic respiratory diseases; however, there was no significant effect on cough outcomes when only data from RCTs were synthesised. We believe that to accurately identify which patients whose cough would benefit from azithromycin a large-scale clinical trial of patients with a broad spectrum of respiratory diseases, with sufficiently severe cough, should be undertaken with subgroup analysis of individual disease areas.
ABSTRACT
PURPOSE: To assess the effects of 1% azithromycin ophthalmic solution (AZM) in patients with bacterial blepharitis accompanied by meibomian gland dysfunction (MGD). STUDY DESIGN: A multicenter, single arm, prospective interventional study. METHODS: AZM was administered to the affected eyes twice daily for the first 2 days and once daily for the subsequent 12 days. Lid margin hyperaemia/redness, collarette at the root of the eyelashes, conjunctival hyperaemia, foreign body sensation, and epiphora were assessed on Days 1, 14, and 28. The Dry Eye-related Quality of Life Score (DEQS) and objectives related to MGD, including lid vascularity, lid margin irregularity, foaming, lid plugging, keratoconjunctival disorders, Marx line, meibum grade, and tear breakup time, were also assessed. Bacterial culture of the conjunctival sac and meibum was performed on Days 1 and 14. RESULTS: Twenty-four eyes of 24 patients (10 men/14 women, mean age 72.3 ± 13.2) were included. On Days 14 and 28, the total score, lid vascularity, lid plugging, and meibum grade showed significant improvement (p < 0.05). On Day 1, 71 strains were isolated from 22 of the 24 eyes (91.7%). Cutibacterium acnes, Corynebacterium spp., and Staphylococci were detected at high frequencies. The overall disappearance rates of the bacteria in the conjunctival sac and meibum at the end of treatment were 65.7% and 58.3%, respectively. No serious ocular or systemic adverse events were observed. CONCLUSION: Fourteen-day treatment with AZM was effective in patients with blepharitis accompanied by MGD, and the efficacy of AZM persisted for a period after the treatment.
ABSTRACT
Despite the increasing incidence of simultaneous mycobacterial and non-mycobacterial tuberculosis (TB) infection, little literature is available exploring the topic. Here, we present a case of a 22-year-old female diagnosed with pulmonary TB for four months with simultaneous multiple sputum cultures positive for non-tuberculous mycobacteria (NTM). Computed tomography of the chest without contrast reported linear areas of scarring involving both lung apices, more prominent on the left side. The patient completed intensive phase treatment for TB and is currently on isoniazid and rifampin with a referral to an infectious disease specialist for recommendations on treatment of Mycobacterium avium regimen in view of azithromycin allergy (intense cough and rash). While the coexistence of NTM is commonly attributed to colonization, differentiating colonization from disease is crucial considering the long duration of treatment, potential drug toxicity, risk of drug resistance, and significant cost of treatment. Clinical, microbiological, and radiological evidence should be considered for diagnosis of TB and NTM coinfection and expert consultation should be sought in formulating the treatment plan.
ABSTRACT
BACKGROUND: Tolerance enables bacteria to survive intermittent antibiotic exposure without an increase in antimicrobial susceptibility. In this study, we investigated the presence of tolerance to three antimicrobials, ceftriaxone, azithromycin and ciprofloxacin, in clinical isolates and the WHO (World Health Organization) reference panel of Neisseria gonorrhoeae. METHODS: We used the modified tolerance disk (TD test) to assess for tolerance to ceftriaxone, azithromycin and ciprofloxacin in 14 WHO reference strains and 62 N. gonorrhoeae clinical isolates-evenly divided between anorectal and urogenital infections. The isolates underwent a three-step incubation process wherein the isolates were exposed to an antibiotic disk for 20 h of incubation (Step I), followed by the replacement of the antibiotic disk with a nutrient disk for overnight incubation (Step II) and additional overnight incubation with extra nutrients (Step III). RESULTS: A total of 4 of the 62 clinical anorectal isolates and none of the urogenital isolates exhibited tolerance to azithromycin (p = 0.033). Tolerance to ceftriaxone and ciprofloxacin was observed in eight and four isolates, respectively, with no difference between infection sites. Tolerance was also detected in 8 (K, M, N, O, P, U, V, W) out of the 14 WHO reference strains, with varying patterns of tolerance to ceftriaxone (n = 8), ciprofloxacin (n = 2) and azithromycin (n = 1). CONCLUSIONS: This study identified ceftriaxone, azithromycin and ciprofloxacin tolerance in clinical and WHO reference N. gonorrhoeae isolates. Azithromycin tolerance was more common in anorectal than urogenital infections.
ABSTRACT
Babesia gibsoni is a parasitic protozoan transmitted through tick bites and can cause severe disease in dogs. It can also be transmitted through direct contact with infected blood during dog fights, blood transfusions, and from dam to offspring during the perinatal period, resulting in stillborn or dead newborn puppies. This study aimed to determine the incidence of infection, the viability of newborn puppies, and the degree of B. gibsoni transmission from infected dam to offspring during pregnancy and lactation. Using PCR-based molecular methods, B. gibsoni infection in a pregnant American Pit Bull Terrier and her newborn puppies was confirmed. The incidence of B. gibsoni infection in the litter reached 75%. Out of eight puppies, six were infected with B. gibsoni, and one died. A therapeutic protocol comprising Malarone®, azithromycin, and artesunate was administered to a lactating B. gibsoni-positive bitch. By day 77 after birth, three out of five positive puppies showed negative PCR tests for B. gibsoni, indicating successful treatment through breast milk during nursing. In the two remaining positive puppies, therapy was started and parasitemia was successfully eliminated.
ABSTRACT
Objective: Mycoplasma pneumoniae (MP) is highly resistant to macrolides in China. However, macrolides still exhibit clinical effectiveness in some macrolide-resistant patients. We tend to explore azithromycin effectiveness in Mycoplasma pneumoniae pneumonia (MPP) children with A2063/2064G mutation. Methods: This retrospective observational cohort study was conducted at the Children's Hospital of the Chongqing Medical University. Children with macrolide-resistant mutations (A2063/2064G) diagnosed as MPP were retrospectively enrolled. Receiver operating characteristic (ROC) curves and logistic regression analysis were used to evaluate and identify independent risk factors for treatment failure (progress to refractory Mycoplasma pneumoniae pneumonia [RMPP]) in macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP) children with the A2063/2064G mutation. Results: One hundred fifty-five children were retrospectively enrolled. More than 20% (36/155, 23.23%) of patients experienced defervescence within 3 days of azithromycin treatment. RMPP was diagnosed in 54 patients (54/155, 34.84%) and the incidence of RMPP during hospitalization was 22.72 per 1000 person-days. Logistic regression analysis showed that lactate dehydrogenase (LDH) ≥ 399 (U/L) was an independent risk factor for RMPP (odds ratio [OR] 4.66, 95% confidence interval [CI] 1.31-17.10, P=0.017). During the year followed, RMPP patients had a significantly higher incidence of bronchiolitis obliterans and bronchiectasis than non-RMPP patients (16.67% vs 1.98%, P=0.001; 9.26% vs 0.00%, P=0.005, respectively). Conclusion: Azithromycin was effective in children with MPP with the A2063/2064G mutation. For MUMPP children with A2063/2064G mutation, children with LDH ≥ 399 (U/L) had significant higher risk for progression to RMPP, and should consider to be treated with alternative antibiotics (eg tetracyclines, and fluoroquinolones).
ABSTRACT
Azithromycin traditional formulations possesses poor oral bioavailability which necessitates development of new formulation with enhanced bioavailability of the drug. The objective of current research was to explore the kinetics and safety profile of the newly developed azithromycin lipid-based nanoformulation (AZM-NF). In the in-vitro study of kinetics profiling, azithromycin (AZM) release was assessed using dialysis membrane enclosing equal quantity of either AZM-NF, oral suspension of azithromycin commercial product (AZM-CP), or azithromycin pure drug (AZM-PD) in simulated intestinal fluid. The ex-vivo study was performed using rabbit intestinal segments in physiological salts solution in a tissue bath. The in-vivo study was investigated by oral administration of AZM to rabbits while taking blood samples at predetermined time-intervals, followed by HPLC analysis. The toxicity study was conducted in rats to observe histopathological changes in rat's internal organs. In the in-vitro study, maximum release was 95.38 ± 4.58% for AZM-NF, 72.79 ± 8.85% for AZM-CP, and 46.13 ± 8.19% for AZM-PD (p < 0.0001). The ex-vivo investigation revealed maximum permeation of 85.68 ± 5.87 for AZM-NF and 64.88 ± 5.87% for AZM-CP (p < 0.001). The in-vivo kinetics showed Cmax 0.738 ± 0.038, and 0.599 ± 0.082 µg/ml with Tmax of 4 and 2 h for AZM-NF and AZM-CP respectively (p < 0.01). Histopathological examination revealed compromised myocardial fibers integrity by AZM-CP only, liver and kidney showed mild aberrations by both formulations, with no remarkable changes in the rest of studied organs. The results showed that AZM-NF exhibited significantly enhanced bioavailability with comparative safer profile to AZM-CP investigated.
Subject(s)
Azithromycin , Biological Availability , Lipids , Nanoparticles , Animals , Azithromycin/pharmacokinetics , Azithromycin/administration & dosage , Azithromycin/chemistry , Rabbits , Rats , Lipids/chemistry , Administration, Oral , Male , Nanoparticles/chemistry , Chemistry, Pharmaceutical/methods , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/administration & dosage , Drug Carriers/chemistry , Drug LiberationABSTRACT
BACKGROUND: Seven 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). OBJECTIVE: We 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 DESIGN: This 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. RESULTS: The 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). CONCLUSION: 500mg 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.