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.

Discovery of the tigecycline resistance gene cluster tmexCD3-toprJ1 in Pasteurella multocida strains isolated from pigs in China.

Pasteurella multocida is a leading cause of respiratory disorders in pigs. However, the genotypes and antimicrobial resistance characteristics of P. multocida from pigs in China have not been reported frequently. In this study, we investigated 381 porcine strains of P. multocida collected in China between 2013 and 2022. These strains were assigned to capsular genotypes A (69.55%, n = 265), D (27.82%, n =106), and F (2.62%, n = 10); or lipopolysaccharide genotypes L1 (1.31%, n = 5), L3 (24.41%, n = 93), and L6 (74.28%, n = 283). Overall, P. multocida genotype A:L6 (46.46%) was the most-commonly identified type, followed by D:L6 (27.82%), A:L3 (21.78%), F:L3 (2.62%), and A:L1 (1.31%). Antimicrobial susceptibility testing showed that a relatively high proportion of strains were resistant to tetracycline (66.67%, n = 254), and florfenicol (35.17%, n = 134), while a small proportion of strains showed resistance phenotypes to enrofloxacin (10.76%, n = 41), ampicillin (8.40%, n = 32), tilmicosin (7.09%, n = 27), and ceftiofur (2.89%, n = 11). Notably, Illumina short-read and Nanopore long-read sequencing identified a chromosome-borne tigecycline-resistance gene cluster tmexCD3-toprJ1 in P. multocida. The structure of this cluster was highly similar to the respective structures found in several members of Proteus or Pseudomonas. It is assumed that the current study identified the tmexCD3-toprJ1 cluster for the first time in P. multocida.

Rare case of septic shock combined with meningitis caused by Pasteurella multocida without a history of cat and dog bites.

BACKGROUND: Pasteurella multocida is a zoonotic pathogen that mainly causes local skin and soft tissue infections in the human body through cat and dog bites. It rarely causes bacteraemia (or sepsis) and meningitis. We reported a case of septic shock and meningitis caused by P. multocida in a patient without a history of cat and dog bites. CASE PRESENTATION: An 84-year-old male patient was urgently sent to the emergency department after he was found with unclear consciousness for 8 h, accompanied by limb tremors and urinary incontinence. In the subsequent examination, P. multocida was detected in the blood culture and wound secretion samples of the patient. However, it was not detected in the cerebrospinal fluid culture, but its DNA sequence was detected. Therefore, the patient was clearly diagnosed with septic shock and meningitis caused by P. multocida. The patient had no history of cat or dog contact or bite. The patient was subsequently treated with a combination of penicillin G, doxycycline, and ceftriaxone, and he was discharged after 35 days of hospitalisation. CONCLUSION: This report presented a rare case of septic shock and meningitis caused by P. multocida, which was not related to a cat or dog bite. Clinical doctors should consider P. multocida as a possible cause of sepsis or meningitis and should be aware of its potential seriousness even in the absence of animal bites.

Pasteurella multocida bacteraemia with liver abscess.

A previously healthy woman in her mid-70s presented with right upper quadrant abdominal pain, fever, intermittent chills and malaise for 1 week. She was clinically septic with raised inflammatory markers. Her blood culture revealed Pasteurella multocida, which was susceptible to penicillin and amoxicillin-clavulanic acid. CT of liver revealed an abscess of 8.0×7.9×8.5 cm at the left lobe of the liver. However, the abscess was not amenable for surgical or radiological drainage. She was a farmer and had close contact with her pet cats. She was occasionally scratched by her cats when caring for them. The liver abscess resolved completely without drainage after prolonged antimicrobial therapy of 109 days. She commenced on 63 days of intravenous antimicrobials and 46 days of oral amoxicillin-clavulanic acid. This case illustrated P. multocida bacteraemia with a large liver abscess in an immunocompetent adult after non-bite exposure.

Bloodstream infection, peritonitis, and pneumonia caused by Pasteurella multocida in a patient with liver cirrhosis despite no animal contact: case report and literature review.

Pasteurella multocida is an opportunistic pathogen. Previously reported infections associated with P. multocida have often been linked to contact with cats, dogs, and other animals. Cases of systemic multiple-site infections following P. multocida infection are rare. This case study presents a 49-year-old middle-aged man with post-hepatitis B cirrhosis and no history of animal contact. The patient was admitted with symptoms of fever accompanied by diarrhea, abdominal distension, and cough. Blood tests showed elevated levels of CRP, PCT, and IL-6, and blood culture revealed the growth of P. multocida. CT scans revealed a large amount of abdominal effusion, a small amount of pleural effusion, and pulmonary infection foci. The patient's condition improved after successive administration of ceftriaxone and levofloxacin to fight the infection, and abdominal puncture and drainage. Multiple-site infections caused by P. multocida are rarely encountered in patients with liver cirrhosis but without animal contact, which could be regarded as serious conditions warranting careful attention in terms of clinical diagnosis and treatment.

Pediatric Pasteurella canis endophthalmitis.

We report an atypical presentation of endophthalmitis in a 2-month-old infant due to a rare infection by Pasteurella canis, small Gram-negative coccobacilli that inhabit the oral cavity and the gastrointestinal tracts of animals, including domesticated cats and dogs. Ocular infections are mainly associated with animal bites and scratches.

Post-Operative Wound Infection by Multiple Zoonotic Organisms.

Rhodococcus hoagii (formerly Rhodococcus equi), originally isolated from equine species, is primarily transmitted through inhalation of contaminated aerosols such as dust and even breath of infected livestock. Pasteurella multocida is a common cause of cellulitis secondary to canine and feline bites. These are 2 zoonotic microbes that can present with potentially life-threatening, systematic illness in immunocompromised patients.In this brief report, we delineate the clinical course of a 42-year-old post-operative patient (status post-elective exploratory laparotomy, extensive adhesiolysis, and excision of enterocutaneous fistula with creation of an end ileostomy) who developed multiple infections involving these two zoonotic microbes. The patient is an enthusiast of exotic animals with an extensive occupational history as a zookeeper. She was determined to be HIV negative but has a significant history of Crohn's disease managed with systemic immunosuppressive therapy. This case highlights her unusual constellation of post-operative infections and her subsequent medical management.

Pasteurella multocida as a Rare Cause of Neonatal Meningitis Complicated by Empyema.

A neonatal male injured by the family dog developed meningitis secondary to Pasteurella multocida . After initially defervescing with IV antibiotic treatment, he became febrile again, and imaging revealed a skull fracture and fluid collection. Following neurosurgical evacuation and an extended course of antibiotics, the patient was discharged home.

Pasteurella multocida Bacterial Meningitis in a 33-Day-Old Infant.

A 33-day-old previously healthy term female is admitted to the pediatric intensive care unit with fever, lethargy and bulging fontanel. Given concern for meningitis, a lumbar puncture is performed and empiric treatment is initiated. The cerebrospinal fluid culture results reveal Pasteurella multocida. The patient is treated with intravenous ampicillin for 3 weeks and discharged with close outpatient follow-up.

Treatment of Pasteurella multocida infection with dressings containing honey and antibacterials: a case report.

Infections secondary to Pasteurella multocida frequently occur in patients who have been exposed to domestic pets. Human infections caused by Pasteurella multocida vary in severity, and clinical features include localised cellulitis, osteomyelitis, systemic bacteraemia, meningitis and pneumonia. No vaccine has been developed against Pasteurella multocida; it is treated with antibacterial agents and, in most cases, surgical intervention. This article discusses the authors' experience in treating a woman with severe cellulitis and osteomyelitis on her hand caused by Pasteurella multocida. She refused surgical intervention and was successfully treated with honey-containing dressings and antibiotics after failure to heal following conservative treatment using conventional wound dressings combined with antibiotics.

[Description of the case of adverse pasteurellosis in a cirrhosis patient. Case report].

The article describes a clinical case of an unfavorable course of pasteurellosis in a patient with liver cirrhosis. Possible variants of the clinical course, clinical and epidemiological data, on the basis of which pasteurellosis can be suspected, modern recommendations for antibiotic therapy are considered.

Novel multi-strain probiotics reduces Pasteurella multocida induced fowl cholera mortality in broilers.

Pasteurella multocida causes fowl cholera, a highly contagious poultry disease of global concern, causing significant ecological and economic challenges to the poultry industry each year. This study evaluated the effects of novel multi-strain probiotics consisting of Lactobacillus plantarum, L. fermentum, Pediococcus acidilactici, Enterococcus faecium and Saccharomyces cerevisiae on growth performance, intestinal microbiota, haemato-biochemical parameters and anti-inflammatory properties on broilers experimentally challenged with P. multocida. A total of 120 birds were fed with a basal diet supplemented with probiotics (108 CFU/kg) and then orally challenged with 108 CFU/mL of P. multocida. Probiotics supplementation significantly (P < 0.05) improved growth performance and feed efficiency as well as reducing (P < 0.05) the population of intestinal P. multocida, enterobacteria, and mortality. Haemato-biochemical parameters including total cholesterol, white blood cells (WBC), proteins, glucose, packed cell volume (PCV) and lymphocytes improved (P < 0.05) among probiotic fed birds when compared with the controls. Transcriptional profiles of anti-inflammatory genes including hypoxia inducible factor 1 alpha (HIF1A), tumor necrosis factor- (TNF) stimulated gene-6 (TSG-6) and prostaglandin E receptor 2 (PTGER2) in the intestinal mucosa were upregulated (P < 0.05) in probiotics fed birds. The dietary inclusion of the novel multi-strain probiotics improves growth performance, feed efficiency and intestinal health while attenuating inflammatory reaction, clinical signs and mortality associated with P. multocida infection in broilers.

Efficacy of grape seed hydro-alcoholic extract in the treatment of experimentally Pasteurella multocida infected rabbits.

Pasteurellosis is one of the rabbit's most bacterial severe diseases and leads to considerable financial damages in large production systems worldwide. Antibiotic use in animals may lead to antibiotic residues in animal products, including meat. Therefore, this study was designed to evaluate the potential role of grape seed extract (GSE) in treating Pasteurella multocida infection in rabbits. For this purpose, 45 weaned male New Zealand rabbits were divided into three groups; control, infected and infected-GSE treated. Experimental P. multocida infection in rabbits induced a remarkable decrease in body weight, body weight gain, as well as microcytic hypochromic anaemia, leucocytosis, neutrophilia and lymphocytopenia. Also, a significant increase in the hepatic and renal injury biomarkers, in interleukin-6, total globulin, α, ß and γ globulins, as well as a marked reduction in total protein and albumin, were recorded in the P. multocida-infected rabbits. Treatment of infected rabbits with GSE modulated most of these altered parameters. This study endorses the administration of GSE for the treatment of Pasteurellosis in rabbits. Further studies are required to identify the possible additional effects, appropriate doses and duration of the GSE therapy in rabbits Pasteurellosis.