Laboratory diagnosis and treatment of Mycoplasma pneumoniae infection in children: a review.

Mycoplasma pneumoniae (MP) is the cause of Mycoplasma pneumoniae pneumonia (MPP) in children and adolescents, with the clinical manifestations highlighted by intermittent irritating cough, accompanied by headache, fever and muscle pain. This paper aimed to study the research status and focal points in MP infection, especially the common laboratory diagnostic methods and clinical treatment of Mycoplasma pneumoniae. Laboratory diagnostic methods include molecular assay, serological antibody detection, rapid antigen detection and isolation and culture. Polymerase chain reaction (PCR) is the gold standard with high sensitivity and specificity. The serological antibody can detect various immune antibodies qualitatively or quantitatively in serum. Rapid antigen can be detected faster, with no equipment environment requirements, which can be used for the early diagnosis of MP infection. While the culture growth cycle is long and insensitive, not recommended for routine diagnosis. Macrolides were the preferred drug for children with MPP, while the drug resistance rate was rising in China. Tetracycline can be substituted but was not recommended for children under 8 years of age, quinolone drugs are not necessary, severe MPP can be combined with glucocorticoids, involving the nervous or immune system can choose gamma globulin. Other treatments for MPP including symptomatic treatment which can alleviate symptoms, improve lung function and improve prognosis. A safe and effective vaccine needed to be developed which can provide protective immunity to children and will reduce the incidence of MPP.

Current Mycoplasma pneumoniae outbreak: Don't forget its role in Bickerstaff encephalitis.

Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in children and young adults. It is responsible of a broad array of extrapulmonary manifestations, the most severe affecting the central nervous system. We report a challenging diagnosis of macrolide-resistant M. pneumoniae-induced Bickerstaff encephalitis in a 16-year-old man.

Macrolide-Resistant Mycoplasma pneumoniae Infections among Children before and during COVID-19 Pandemic, Taiwan, 2017-2023.

Before the COVID-19 pandemic, Mycoplasma pneumoniae infections emerged during spring to summer yearly in Taiwan, but infections were few during the pandemic. M. pneumoniae macrolide resistance soared to 85.7% in 2020 but declined to 0% during 2022-2023. Continued molecular surveillance is necessary to monitor trends in macrolide-resistant M. pneumoniae.

Clinical efficacy of macrolide antibiotics in mycoplasma pneumoniae pneumonia carrying a macrolide-resistant mutation in the 23 S rRNA gene in pediatric patients.

BACKGROUND: The global prospective surveillance data showed the re-emergence of mycoplasma pneumoniae pneumonia (MPP) in Europe and Asia after the coronavirus disease 2019 pandemic. We sought to observe the effect of macrolide antibiotics in the treatment of MPP carrying a macrolide-resistant mutation gene and the potential of targeted next-generation sequencing (tNGS) as a front-line diagnostic in MPP patients. METHODS: The baseline characteristics of 91 children with MPP hospitalized from January to October 2023 were retrospectively analyzed. They were divided into two groups according to whether carrying the macrolide-resistant mutation or not. The logistic and linear regression analyses were used to determine whether the mutation was a standalone predictive predictor of the duration of fever and hospital length of stay. RESULTS: First, no patients had a fever for ≥ 7 days after macrolide treatment. But length of stay and hormone concentration were significantly different between the two groups (P < 0.05). There were also no statistical association between the mutation and the duration of fever and hospital length of stay. CONCLUSION: Macrolides can be administered to MPP children carrying a macrolide-resistant mutation. tNGS can be seen as a front-line diagnostic in MPP.

Exploring Splicing Modulation as an Innovative Approach to Combat Pancreatic Cancer: SF3B1 Emerges as a Prognostic Indicator and Therapeutic Target.

Pancreatic ductal adenocarcinoma (PDAC) poses significant challenges in terms of prognosis and treatment. Recent research has identified splicing deregulation as a new cancer hallmark. Herein, we investigated the largely uncharacterized alternative splicing profile and the key splicing factor SF3B1 in PDAC pancreatic cells and tissues as a potential discovery source of plausible drug targets and new predictive biomarkers of clinical outcome. The research involved a transcriptome-wide analysis, comparing profiles of splicing profiles in PDAC primary cells with normal ductal cells. This revealed more than 400 significant differential splicing events in genes involved in regulation of gene expression, primarily related to mRNA splicing, and metabolism of nucleic acids. PDAC cultures were highly sensitive to the SF3B1 modulators, E7107 and Pladienolide-B, showing IC50s in the low nanomolar range. These compounds induced apoptosis, associated to induction of the MCL-1/S splice variant. and reduced cell migration, associated to RON mis-splicing. In an orthotopic mouse model, E7107 showed promising results. Furthermore, we evaluated SF3B1 expression in specimens from 87 patients and found a significant association of SF3B1 expression with progression-free and overall survival. In conclusion, SF3B1 emerges as both a potential prognostic factor and therapeutic target in PDAC, impacting cell proliferation, migration, and apoptosis. These findings warrant future studies on this new therapeutic strategy against PDAC.

Cost-effectiveness of resistance-guided therapy for Mycoplasma genitalium in Australia.

The recommended first-line treatment for Mycoplasma genitalium infections is azithromycin. However, the prevalence of macrolide resistance for M. genitalium has increased to more than 50% worldwide. In 2013, Australia introduced a resistance-guided therapy (RGT) strategy to manage M. genitalium infections. This study assesses the cost-effectiveness of the RGT approach compared to no RGT (i.e., without macrolide resistance profile test) in women, men who have sex with men (MSM), and men who have sex with women (MSW) in Australia. We constructed dynamic transmission models of M. genitalium infections in women, MSM, and MSW in Australia, each with a population of 100,000. These models compared the costs and quality-adjusted life-years (QALYs) gained between RGT and no RGT scenarios from a healthcare perspective over ten years. All costs are reported in 2022 Australian dollars (Australian $). In our model, RGT is cost saving in women and MSM, with the incremental net monetary benefit of $1.3 million and $17.9 million, respectively. In MSW, the RGT approach is not cost-effective, with an incremental cost-effectiveness ratio of -$106.96 per QALY gained. RGT is cost saving compared to no RGT for M. genitalium infections in women and MSM, supporting its adoption as the national management strategy for these two population groups.

Role of Inositol-Requiring Enzyme 1 and Autophagy in the Pro-Fibrotic Mechanism Underlying Graves' Orbitopathy.

PURPOSE: Orbital fibroblasts play key roles in the pathogenesis of Graves' orbitopathy (GO), and previous findings have shown that endoplasmic reticulum (ER) stress and autophagy also contribute to GO. In this study, we investigated the presently unclear roles of inositol-requiring enzyme 1 (IRE1) and related autophagy processes in the pro-fibrotic mechanism of GO. MATERIALS AND METHODS: Orbital adipose/connective tissues were obtained from eight GO patients and six normal individuals during surgery. GO fibroblasts were transfected with IRE1 small-interfering RNA and treated with bafilomycin A1 (Baf-A1) to evaluate the inhibitory effects of ER stress and autophagy, and protein-expression levels were analyzed through western blotting after stimulation with transforming growth factor (TGF)-ß. RESULTS: TGF-ß stimulation upregulated IRE1 in GO orbital fibroblasts, whereas silencing IRE1 suppressed fibrosis and autophagy responses. Similarly, Baf-A1, an inhibitor of late-phase autophagy, decreased the expression of pro-fibrotic proteins. CONCLUSION: IRE1 mediates autophagy and the pro-fibrotic mechanism of GO, which provides a more comprehensive interpretation of GO pathogenesis and suggests potential therapeutic targets.

Inefficacy of ivermectin and moxidectin treatments against Dictyocaulus viviparus in dairy calves.

BACKGROUND: The bovine lungworm Dictyocaulus viviparus negatively impacts bovine health and leads to substantial economic losses. Lungworm infections can be difficult to manage due to the unpredictable and severe nature of clinical outbreaks. Despite the widespread use of macrocyclic lactones (MLs) in grazing cattle in the UK, there have been no confirmed reports of resistant lungworms to date, with only one case of anthelmintic-resistant (ML) lungworm confirmed worldwide. METHODS: Lungworm Baermann filtrations were conducted on first-season grazing dairy calves as part of a wider study investigating anthelmintic resistance in gastrointestinal nematodes in Scotland using the faecal egg count reduction test. RESULTS: Clinical signs and significant numbers of lungworm larvae in faeces were observed after treatment with either ivermectin or moxidectin. LIMITATIONS: There are no established guidelines for the diagnosis of resistant lungworms in the field. Currently, resistance can only be diagnosed after a controlled efficacy test has been conducted. This limits the conclusions that can be drawn; however, they are highly suggestive of resistance. CONCLUSION: This short report describes the inefficacy of ivermectin and moxidectin against D. viviparus and is highly suggestive of ML resistance.

Prolonged mass azithromycin distributions and macrolide resistance determinants among preschool children in Niger: A sub-study of a cluster-randomized trial (MORDOR).

BACKGROUND: Randomized controlled trials found that twice-yearly mass azithromycin administration (MDA) reduces childhood mortality, presumably by reducing infection burden. World Health Organization (WHO) issued conditional guidelines for mass azithromycin administration in high-mortality settings in sub-Saharan Africa given concerns for antibiotic resistance. While prolonged twice-yearly MDA has been shown to increase antibiotic resistance in small randomized controlled trials, the objective of this study was to determine if macrolide and non-macrolide resistance in the gut increases with the duration of azithromycin MDA in a larger setting. METHODS AND FINDINGS: The Macrolide Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) study was conducted in Niger from December 2014 to June 2020. It was a cluster-randomized trial of azithromycin (A) versus placebo (P) aimed at evaluating childhood mortality. This is a sub-study in the MORDOR trial to track changes in antibiotic resistance after prolonged azithromycin MDA. A total of 594 communities were eligible. Children 1 to 59 months in 163 randomly chosen communities were eligible to receive treatment and included in resistance monitoring. Participants, staff, and investigators were masked to treatment allocation. At the conclusion of MORDOR Phase I, by design, all communities received an additional year of twice-yearly azithromycin treatments (Phase II). Thus, at the conclusion of Phase II, the treatment history (1 letter per 6-month period) for the participating communities was either (PP-PP-AA) or (AA-AA-AA). In Phase III, participating communities were then re-randomized to receive either another 3 rounds of azithromycin or placebo, thus resulting in 4 treatment histories: Group 1 (AA-AA-AA-AA-A, N = 51), Group 2 (PP-PP-AA-AA-A, N = 40), Group 3 (AA-AA-AA-PP-P, N = 27), and Group 4 (PP-PP-AA-PP-P, N = 32). Rectal swabs from each child (N = 5,340) were obtained 6 months after the last treatment. Each child contributed 1 rectal swab and these were pooled at the community level, processed for DNA-seq, and analyzed for genetic resistance determinants. The primary prespecified outcome was macrolide resistance determinants in the gut. Secondary outcomes were resistance to beta-lactams and other antibiotic classes. Communities recently randomized to azithromycin (groups 1 and 2) had significantly more macrolide resistance determinants than those recently randomized to placebo (groups 3 and 4) (fold change 2.18, 95% CI 1.5 to 3.51, Punadj < 0.001). However, there was no significant increase in macrolide resistance in communities treated 4.5 years (group 1) compared to just the most recent 2.5 years (group 2) (fold change 0.80, 95% CI 0.50 to 1.00, Padj = 0.010), or between communities that had been treated for 3 years in the past (group 3) versus just 1 year in the past (group 4) (fold change 1.00, 95% CI 0.78 to 2.35, Padj = 0.52). We also found no significant differences for beta-lactams or other antibiotic classes. The main limitations of our study were the absence of phenotypic characterization of resistance, no complete placebo arm, and no monitoring outside of Niger limiting generalizability. CONCLUSIONS: In this study, we observed that mass azithromycin distribution for childhood mortality among preschool children in Niger increased macrolide resistance determinants in the gut but that resistance may plateau after 2 to 3 years of treatment. Co-selection to other classes needs to be monitored. TRIAL REGISTRATION: NCT02047981 https://classic.clinicaltrials.gov/ct2/show/NCT02047981.

Bronchiectasis management in adults: state of the art and future directions.

Formerly regarded as a rare disease, bronchiectasis is increasingly recognised. A renewed interest in this disease has led to significant progress in bronchiectasis research. Randomised clinical trials (RCTs) have demonstrated the benefits of airway clearance techniques, inhaled antibiotics and long-term macrolide therapy in bronchiectasis patients. However, the heterogeneity of bronchiectasis remains one of the most challenging aspects of management. Phenotypes and endotypes of bronchiectasis have been identified to help find "treatable traits" and partially overcome disease complexity. The goals of therapy for bronchiectasis are to reduce the symptom burden, improve quality of life, reduce exacerbations and prevent disease progression. We review the pharmacological and non-pharmacological treatments that can improve mucociliary clearance, reduce airway inflammation and tackle airway infection, the key pathophysiological features of bronchiectasis. There are also promising treatments in development for the management of bronchiectasis, including novel anti-inflammatory therapies. This review provides a critical update on the management of bronchiectasis focusing on treatable traits and recent RCTs.

Moxidectin versus Ivermectin in the prevention and treatment of acute and chronic experimental trichinellosis.

The limited activity of the traditional medications against T. spiralis encysted larvae handicaps complete cure of trichinellosis till now due to decreased permeability and absorption through tissues. MOX is listed worldwide for prevention and treatment of several internal and external nematodes. Consequently, the aim of this work was to investigate the effect of moxidectin versus ivermectin on experimental acute and chronic trichinellosis and to illuminate the potential mechanisms of their effects. 105 Mice were divided into four groups; Group I: Uninfected healthy control; Group II: Infected untreated control; Group III: Infected and treated with IVM and Group IV: Infected and treated with MOX. The groups (II, III and IV) were later subdivided equally into three subgroups (a, b, and c) according to the stage of treatment. Parasitological counting of adults and larvae besides immune-histopathological examination of intestines and muscles were done. Results exhibited that both IVM and MOX succeeded in reducing adults and larvae counts with higher potential of MOX in both intestinal and muscle phase. The preeminence of MOX was indicated by decreased inflammation, a significant reduction in the microvascular density (CD31 immunostaining) as well as a reduction in the percentage of fibroblast activation protein (FAP) immunostaining in muscle tissues. Accordingly, the current work recommends moxidectin as an innovative treatment for trichinellosis.

Immediate and long-term effects of COVID-19 on antibiotic dispensing: increasing use of Watch antibiotics.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic affected antibiotic usage worldwide. However, there is limited data from Serbia. Dispensing of oral antibiotics in Serbian pharmacies was analyzed to calculate monthly and yearly changes between 2018-2021, and to explore immediate and long-term effects of COVID-19 on antibiotic dispensing during this period. METHODOLOGY: The number of antibiotic packages dispensed from pharmacies during the study period was analyzed with a Chi-square test to assess the average change in annual dispensing, and an interrupted time-series analysis was used to evaluate the impact of the pandemic on antibiotic dispensing. The data from 2018-2021 were retrieved from the database of a large community pharmacy chain in Serbia. RESULTS: The average number of antibiotic packages dispensed per day and per pharmacy was higher in 2021 compared to 2018 by one package. However, the dispensing of macrolides increased significantly; 17.7% (2018) vs. 22.5% (2021) (p < 0.05). In general, an increase in antibiotic dispensing was detected during COVID-19 for total antibiotics (16.4%), Watch antibiotics (44.8%), third-generation cephalosporins (80.4%), macrolides (45.5%) and azithromycin (83.7%). However, the immediate effect of COVID-19 was a decrease in the dispensing of Watch antibiotics, penicillin, and third-generation cephalosporins (p < 0.05); and a notable long-term COVID-19 effect was an increase in the dispensing of azithromycin (p < 0.05). CONCLUSIONS: In spite of a relatively stable trend of total antibiotic dispensing before and during COVID-19 pandemic, the use of Watch antibiotics, third-generation cephalosporins, and macrolides (particularly azithromycin) showed an increasing trend in dispensing that should be optimized.

Detection of Macrolide and/or Fluoroquinolone Resistance Genes in Mycoplasma genitalium Strains Isolated from Men in the Northwest Region of Croatia in 2018-2023.

Mycoplasma genitalium (M. genitalium) poses a significant public health challenge due to its association with non-gonococcal urethritis (particularly in men) and antimicrobial resistance. However, despite the prevalence of M. genitalium infections and the rise in resistance rates, routine testing and surveillance remain limited. This is the first study from Croatia that aimed to assess the prevalence and trends of resistance in M. genitalium strains isolated from male individuals by detecting macrolide and fluoroquinolone resistance genes. The study also aimed to explore the factors associated with resistance and changes in resistance patterns over time. Urine samples collected from male individuals in the Zagreb County and northwest region of Croatia between 2018 and 2023 were tested for M. genitalium with the use of molecular methods. Positive samples were subjected to DNA extraction and multiplex tandem polymerase chain reaction (MT-PCR) targeting genetic mutations associated with macrolide (23S rRNA gene) and fluoroquinolone (parC gene) resistance. Of the 8073 urine samples tested from 6480 male individuals (and following the exclusion of repeated specimens), we found that the prevalence of M. genitalium infection was 2.2%. Macrolide resistance was observed in 60.4% of strains, while fluoroquinolone resistance was found in 19.2%. Co-resistance to both antibiotics was present in 18.2% of cases. A statistically significant increase in fluoroquinolone resistance was noted over the study period (p = 0.010), but this was not evident for azithromycin resistance (p = 0.165). There were no statistically significant differences in resistance patterns between age groups, whereas re-testing of patients revealed dynamic changes in resistance profiles over time. The high burden of macrolide resistance and increasing fluoroquinolone resistance underscore the urgent need for comprehensive resistance testing and surveillance programs. The implementation of resistance-guided treatment strategies, along with enhanced access to molecular diagnostics, is pivotal for effectively managing M. genitalium infections.

Challenges in the treatment of pediatric Mycoplasma pneumoniae pneumonia.

Mycoplasma pneumoniae (MP) is an important cause of community-acquired pneumonia in children and young adolescents. Despite macrolide antibiotics effectiveness as a first-line therapy, persistence of fever and/or clinical deterioration sometimes may complicate treatment and may even lead to severe systemic disease. To date, there is no consensus on alternative treatment options, optimal dosage, and duration for treating severe, progressive, and systemic MP pneumonia after macrolide treatment failure. Macrolide-resistant MP pneumonia and refractory MP pneumonia are the two major complex conditions that are clinically encountered. Currently, the vast majority of MP isolates are resistant to macrolides in East Asia, especially China, whereas in Europe and North America, whereas in Europe and North America prevalence is substantially lower than in Asia, varying across countries. The severity of pneumonia and extrapulmonary presentations may reflect the intensity of the host's immune reaction or the dissemination of bacterial infection. Children infected with macrolide-resistant MP strains who receive macrolide treatment experience persistent fever with extended antibiotic therapy and minimal decrease in MP-DNA load. Alternative second-line agents such as tetracyclines (doxycycline or minocycline) and fluoroquinolones (ciprofloxacin or levofloxacin) may lead to clinical improvement after macrolide treatment failure in children. Refractory MP pneumonia reflects a deterioration of clinical and radiological findings due to excessive immune response against the infection. Immunomodulators such as corticosteroids and intravenous immunoglobulin (IVIG) have shown promising results in treatment of refractory MP pneumonia, particularly when combined with appropriate antimicrobials. Corticosteroid-resistant hyperinflammatory MP pneumonia represents a persistent or recrudescent fever despite corticosteroid therapy with intravenous methylprednisolone at standard dosage. CONCLUSION:  This report summarizes the clinical significance of macrolide-resistant and refractory MP pneumonia and discusses the efficacy and safety of alternative drugs, with a stepwise approach to the management of MP pneumonia recommended from the viewpoint of clinical practice. WHAT IS KNOWN: • Although MP pneumonia is usually a benign self-limited infection with response macrolides as first line therapy, severe life-threatening cases may develop if additional treatment strategies are not effectively implemented. • Macrolide-resistant and refractory MP pneumonia are two conditions that may complicate the clinical course of MP pneumonia, increasing the risk for exacerbation and even death. WHAT IS NEW: • This report summarizes the clinical relevance of macrolide-resistant and refractory MP pneumonia and discusses the efficacy and safety of alternative drug therapies. • A practical stepwise approach to the management of MP pneumonia is developed based on a comprehensive analysis of existing evidence and expert opinion.

Mycoplasmoides genitalium Macrolide Resistance Detection is Needed in University Settings.

Background: Mycoplasmoides genitalium remains a difficult sexually-transmitted infection (STI) to manage due to its potential for antimicrobial resistance and post-infection sequelae. University students are especially vulnerable, as this demographic has the highest rate of STI in the United States. As a result, investigating prevalence rates and therapeutic outcomes in this population is essential to minimize future impact of M. genitalium The purpose of this study was to investigate a university student population for M. genitalium distribution and treatment outcome.Design: Retrospective chart-review of university health clinic attendees, augmented by laboratory detection of M. genitalium following therapeutic intervention.Methods: A total of 1617 student encounters at a midwestern United States university health clinic over a 28-month interval from November 2017 through February 2020 were analyzed for M. genitalium and Chlamydia trachomatis positivity rates and prevalence. Detection of these sexually-transmitted pathogens occurred by commercial RNA amplification testing. Chart review was focused on participant outcomes following initial M. genitalium detection and therapeutic intervention.Results: C. trachomatis positivity and prevalence rates were 7.05% and 9.00%, respectively, while analogous rates for M. genitalium were 7.05% and 6.51%, respectively. An average of 1.83 positive results was generated from participants infected with M. genitalium at any time, with an average of 1.17 positive results for C. trachomatis (P < 0.0002). For students treated with azithromycin, 30.3% generated a negative M. genitalium result upon follow-up, with 1g daily and 2-day 500mg dosing regimens demonstrating less efficacy than a 4-day 250mg regimen or moxifloxacin.Conclusion: Data indicate a need for molecular M. genitalium macrolide resistance determination from primary specimens in the university setting.

Safety of an oral combination of moxidectin, afoxolaner, and pyrantel pamoate in dogs.

NexGard®PLUS (moxidectin, afoxolaner, and pyrantel pamoate), is an oral combination product for dogs indicated for the prevention of heartworm disease, the treatment and prevention of flea and tick infestations, and the treatment of gastro-intestinal nematode infections. The safety of this product in dogs was evaluated in three studies. Study #1 was a margin-of-safety study conducted in puppies, dosed six times at 28-day intervals at 1X, 3X, or 5X multiples of the maximum exposure dose (equivalent to 24 µg/kg moxidectin, 5 mg/kg afoxolaner, and 10 mg/kg pyrantel). In Study #2, the product was administered to ABCB1-deficient collie dogs at a 1X dose twice at a 28-day interval, and at a 3X or 5X dose once. Study #3 evaluated the safety of the product at 1X and 3X doses administered three times at 4-week intervals, to dogs harboring adult Dirofilaria immitis. In the three studies, the safety was evaluated on the basis of multiple clinical observations and physical examinations, including a complete assessment of toxicity to macrocyclic lactones, and on comprehensive clinical and anatomical pathology evaluations in Study #1. No clinically significant combination product-related effects were observed in any of the three studies. No signs of macrocyclic lactone toxicity were observed in the ABCB1-deficient collie dogs. Some mild and self-resolving instances of emesis or diarrhea were occasionally observed in the 3X and 5X dosed dogs. NexGard® PLUS was demonstrated to be safe following multiple administrations in puppies, in ABCB1-deficient collie dogs, and in microfilaremic dogs infected with adult D. immitis.

Pharmacokinetic/pharmacodynamic evaluation of gamithromycin against rabbit pasteurellosis.

BACKGROUND: Gamithromycin is an effective therapy for bovine and swine respiratory diseases but not utilized for rabbits. Given its potent activity against respiratory pathogens, we sought to determine the pharmacokinetic profiles, antimicrobial activity and target pharmacokinetic/pharmacodynamic (PK/PD) exposures associated with therapeutic effect of gamithromycin against Pasteurella multocida in rabbits. RESULTS: Gamithromycin showed favorable PK properties in rabbits, including high subcutaneous bioavailability (86.7 ± 10.7%) and low plasma protein binding (18.5-31.9%). PK analysis identified a mean plasma peak concentration (Cmax) of 1.64 ± 0.86 mg/L and terminal half-life (T1/2) of 31.5 ± 5.74 h after subcutaneous injection. For P. multocida, short post-antibiotic effects (PAE) (1.1-5.3 h) and post-antibiotic sub-inhibitory concentration effects (PA-SME) (6.6-9.1 h) were observed after exposure to gamithromycin at 1 to 4× minimal inhibitory concentration (MIC). Gamithromycin demonstrated concentration-dependent bactericidal activity and the PK/PD index area under the concentration-time curve over 24 h (AUC24h)/MIC correlated well with efficacy (R2 > 0.99). The plasma AUC24h/MIC ratios of gamithromycin associated with the bacteriostatic, bactericidal and bacterial eradication against P. multocida were 15.4, 24.9 and 27.8 h in rabbits, respectively. CONCLUSIONS: Subcutaneous administration of 6 mg/kg gamithromycin reached therapeutic concentrations in rabbit plasma against P. multocida. The PK/PD ratios determined herein in combination with ex vivo activity and favorable rabbit PK indicate that gamithromycin may be used for the treatment of rabbit pasteurellosis.