In vitro synergism of fosfomycin and clarithromycin antimicrobials against methicillin-resistant Staphylococcus pseudintermedius

BACKGROUND: Bacterial biofilms are of tremendous concern for clinicians, as they can compromise the ability of the immune system and antimicrobial therapy to resolve chronic and recurrent infections. Novel antimicrobial therapies or combinations targeted against biofilm establishment and growth subsequently represent a promising new option for the treatment of chronic infectious diseases. In this study, we treated bacterial biofilms produced by methicillin-resistant Staphylococcus pseudintermedius (MRSP) with a combination of fosfomycin and clarithromycin. We selected these agents, because they prevent biofilm formation and induce antimicrobial synergism that may also target other staphylococci. RESULTS: We determined that the combination of fosfomycin and clarithromycin better impairs S. pseudintermedius biofilm formation compared to treatment with either therapy alone (P < 0.05). Morphological examination of these biofilms via scanning electron microscopy demonstrated that fosfomycin alone does impact biofilm formation on orthopaedic implants. However, this activity is enhanced in the presence of clarithromycin. We propose that the bacteriostatic activity of clarithromycin is accentuated when fosfoymcin is present, as it may allow better penetration into the biofilm matrix, allowing fosfomycin access to sessile bacteria near the surface of attachment. CONCLUSIONS: Here, we demonstrate that the combination of fosfomycin and clarithromycin may be a useful therapy that could improve the clinical outcomes of treating antimicrobial resistant MRSP biofilms

Characterization of the biofilm forming ability of Staphylococcus pseudintermedius from dogs

BACKGROUND: Staphylococcus pseudintermedius is an opportunistic pathogen of dogs and has emerged as a leading cause of skin, wound and surgical site infections worldwide. Methicillin resistance is common and clinical infections as a result of methicillin-resistant S. pseudintermedius (MRSP) pose a clinical challenge. In other staphylococci, biofilm formation has been shown to be a virulence factor for infection, however, it has received little attention in S. pseudintermedius. The objectives of this study were to evaluate the biofilm forming ability of clinical isolates of S. pseudintermedius obtained from dogs using phenotypic and genotypic techniques. RESULTS: 96% (136/140) of S. pseudintermedius isolates were classified as strong or moderate biofilm producers, with the majority of isolates being able to produce biofilm. There was no difference in biofilm formation between MRSP and MSSP (p=0.8), amongst isolates from clinical infections compared with isolates obtained from colonized dogs (p=0.08), and between isolates from sequence type (ST) 71 and ST 68 (P=0.09). icaA was detected in 77.9% (109/140) of isolates and icaD was detected in 75.7% (106/140) of isolates. Scanning electron microscopic evaluation of S. pseudintermedius biofilm production revealed aggregates of cocci and irregularly produced extracellular polymeric matrix. CONCLUSION: The majority of S. pseudintermedius isolates evaluated in this study were able to produce biofilm and this may be an important virulence factor in the rapid emergence of this bacterium in veterinary hospitals worldwide. Further study into the mechanisms of biofilm formation by S. pseudintermedius is warranted

A systematic review of criteria used to report complications in soft tissue and oncologic surgical clinical research studies in dogs and cats.

ObjectiveTo evaluate reporting of surgical complications and other adverse events in clinical research articles describing soft tissue and oncologic surgery in dogs and cats.Study designSystematic literature review.SampleEnglish-language articles describing soft tissue and oncologic surgeries in client-owned dogs and cats published in peer-reviewed journals from 2013 to 2016.MethodsCAB, AGRICOLA, and MEDLINE databases were searched for eligible articles. Article characteristics relevant to complications were abstracted and summarized, including reported events, definitions, criteria used to classify events according to severity and time frame, and relevant citations.ResultsOne hundred fifty-one articles involving 10 522 animals were included. Canine retrospective case series of dogs predominated. Ninety-two percent of articles mentioned complications in study results, but only 7.3% defined the term complication. Articles commonly described complications according to time frame and severity, but terminology and classification criteria were highly variable, conflicting between studies, or not provided. Most (58%) reported complications could have been graded with a published veterinary adverse event classification scheme, although common intraoperative complications were notable exceptions.ConclusionDefinitions and criteria used to classify and report soft tissue and oncologic surgical complications are often absent, incomplete, or contradictory among studies.Clinical significanceLack of consistent terminology contributes to inadequate communication of important information about surgical complications. Standardization of terminology and consistency in severity scoring will improve comparative evaluation of clinical research results

In vitro synergism of fosfomycin and clarithromycin antimicrobials against methicillin-resistant Staphylococcus pseudintermedius

Abstract Background: Bacterial biofilms are of tremendous concern for clinicians, as they can compromise the ability of the immune system and antimicrobial therapy to resolve chronic and recurrent infections. Novel antimicrobial therapies or combinations targeted against biofilm establishment and growth subsequently represent a promising new option for the treatment of chronic infectious diseases. In this study, we treated bacterial biofilms produced by methicillin-resistant Staphylococcus pseudintermedius (MRSP) with a combination of fosfomycin and clarithromycin. We selected these agents, because they prevent biofilm formation and induce antimicrobial synergism that may also target other staphylococci. Results: We determined that the combination of fosfomycin and clarithromycin better impairs S. pseudintermedius biofilm formation compared to treatment with either therapy alone (P &lt; 0.05). Morphological examination of these biofilms via scanning electron microscopy demonstrated that fosfomycin alone does impact biofilm formation on orthopaedic implants. However, this activity is enhanced in the presence of clarithromycin. We propose that the bacteriostatic activity of clarithromycin is accentuated when fosfoymcin is present, as it may allow better penetration into the biofilm matrix, allowing fosfomycin access to sessile bacteria near the surface of attachment. Conclusions: Here, we demonstrate that the combination of fosfomycin and clarithromycin may be a useful therapy that could improve the clinical outcomes of treating antimicrobial resistant MRSP biofilms

Preterm birth among pregnancies conceived by assisted reproduction techniques in Mumbai, Maharashtra, India

Background: Preterm births are an enormous global problem on families, medical system and economy. The rates of preterm birth are increasing and one of the contributors is growing use of Assisted Reproduction Techniques (ART) leading to multifetal gestations. Some risk factors for preterm birth are specific to women who conceive by ART. Since there is limited data from India, this pilot study was undertaken to assess the magnitude of preterm birth among pregnancies conceived by ART and to study the contributing factors.Methods: Clinic based descriptive cohort study through eight ART clinics in Mumbai for one year. Data was collected using an in-depth questionnaire on socio-demographic characteristics, medical history, ART details, course and complications during pregnancy, mode of delivery, pregnancy outcome, risk factors related to preterm birth and neonatal outcome. Complete details of 113 participants who completed the study were analyzed.Results: Study showed high incidence of preterm birth (76.23%) among women conceived with ART. Multiple gestations were observed in 45.1%. Pregnancy related complications like heterotrophic pregnancy (3%), pre eclampsia (15%) and gestational diabetes (11%) were high. Incidence of caesarean section was very high (98%). Neonatal outcome was good with 98% live births and only 2 still births.Conclusions: Present study highlights that preterm birth, multiple pregnancies, pregnancy related complications like preeclampsia, gestational diabetes and caesarean sections are very high among women conceived by ART. With growing use of ART there is an urgent need to develop a National ART Surveillance system in India like the one in Centre for Disease Control Atlanta to get complete data on the pregnancy course and outcomes of ART conceptions. Efforts to limit the number of embryos transferred should be strengthened to prevent multiple births

The effect of prophylactic treatment with levetiracetam on the incidence of post-attenuation seizures in dogs undergoing surgical management of single congenital extrahepatic portosystemic shunts

Objectives: To report (1) the incidence of post-attenuation seizures (PAS) in dogs that underwent single congenital extrahepatic portosystemic shunt (cEHPSS) attenuation and (2) to compare incidence of PAS in dogs that either did or did not receive prophylactic treatment with levetiracetam (LEV).Study Design: Multi-institutional retrospective study.Sample Population: Nine-hundred-and-forty dogs.Methods: Medical records were reviewed to identify dogs that underwent surgical attenuation of a single cEHPSS from January 2005 through July 2017 and developed PAS within seven days postoperatively. Dogs were divided into three groups: no LEV (LEV-); LEV at >15mg/kg TID for >24 hours or a 60mg/kg intravenous loading dose preoperatively, followed by >15mg/kg TID postoperatively (LEV1); ); and LEV at less than 15mg/kg TID, for less than 24 hours preoperatively, or continued at less than 15mg/kg TID postoperatively (LEV2).Results: Nine-hundred-and-forty dogs were included. Seventy-five (8.0%) developed PAS. Incidence of PAS was 35/523 (6.7%), 21/188 (11.2%) and 19/228 (8.3%) in groups LEV-, LEV1 and LEV2, respectively. This difference was not statistically significant (p=0.14). No significant differences between groups of dogs that seized with respect to variables investigated were identified.Conclusions: The overall incidence of PAS was low (8%). Prophylactic treatment with LEV according to the protocols investigated in our study was not associated with a reduced incidence of PAS.Clinical Significance: Prophylactic treatment with LEV does not afford protection against development of PAS. Surgically treated dogs should continue to be monitored closely during the first seven days postoperatively for seizures

Perioperative characteristics, histologic diagnosis, complications, and outcomes of dogs undergoing percutaneous drainage, sclerotherapy or surgical management of intrarenal cystic lesions: 18 dogs (2004-2021)

BACKGROUND: Canine intrarenal cystic lesions (ICLs) are infrequently reported in the veterinary literature. Several treatment options have been described including cyst fenestration (partial nephrectomy/deroofing) +/- omentalization, sclerotherapy using alcohol as a sclerosing agent, percutaneous cyst drainage (PCD), and ureteronephrectomy. Information regarding presenting clinical signs, physical examination findings, histologic diagnosis and outcomes of dogs with ICLs treated by different methods is limited. Medical records of 11 institutions were retrospectively reviewed to identify dogs that underwent PCD, sclerotherapy, surgical deroofing +/- omentalization, or ureteronephrectomy for management of ICLs from 2004 to 2021. Six weeks postoperative/post-procedural follow-up was required. Cases suspected to represent malignancy on preoperative imaging were excluded. The study objective was to provide information regarding perioperative characteristics, complications, and outcomes of dogs undergoing treatment of ICLs. RESULTS: Eighteen dogs were included, with 24 ICLs treated. Ten had bilateral. There were 15 males and 3 females, with crossbreeds predominating. PCD, sclerotherapy, deroofing and ureteronephrectomy were performed in 5 (5 ICLs treated), 7 (11 ICLs), 6 (6), and 7 (7) dogs, respectively, with 5 dogs undergoing > 1 treatment. Seven dogs experienced 8 complications, with requirement for additional intervention commonest. PCD, sclerotherapy and deroofing resulted in ICL resolution in 0/5, 3/11 and 3/6 treated ICLs, respectively. Histopathology identified renal cysts (RCs) in 7/13 dogs with histopathology available and neoplasia in 6/13 (4 malignant, 2 benign). Of 5 dogs diagnosed histopathologically with neoplasia, cytology of cystic fluid failed to identify neoplastic cells. Among 7 dogs with histologically confirmed RCs, 4 had concurrent ICLs in ipsilateral/contralateral kidney, compared with 2/6 dogs with histologically confirmed neoplasia. CONCLUSIONS: Benign and neoplastic ICLs were approximately equally common and cystic fluid cytology failed to differentiate the 2. Among renal-sparing treatments, deroofing most commonly resulted in ICL resolution. Presence of concurrent ICLs in ipsilateral/contralateral kidney does not appear reliable in differentiating benign from malignant ICLs

Laparoscopic adrenalectomy for resection of unilateral noninvasive adrenal masses in dogs is associated with excellent outcomes in experienced centers

OBJECTIVE: To report the short- and long-term outcomes of laparoscopic adrenalectomy (LA) for resection of unilateral adrenal masses and to document risk factors for conversion and peri- and postoperative morbidity. ANIMALS: 255 client-owned dogs. METHODS: Dogs were included if LA was attempted for resection of a unilateral adrenal mass. Medical records were evaluated and relevant data were reported, including complications, conversion, perioperative death, and long-term outcomes. Signalment, clinicopathological data, and surgical experience were factors statistically evaluated for possible associations with capsular penetration during surgery, conversion, surgical time, duration of hospital stay, death prior to discharge, mass recurrence, and survival time. RESULTS: 155 dogs had left-sided tumors, and 100 had right-sided tumors. Conversion to an open approach was performed in 9.4% of cases. Capsular penetration (19.2%) and major hemorrhage (5.4%) were the most prevalent intraoperative complications. Of the dogs operated on, 94.9% were discharged from the hospital. Lesion side, portion of the gland affected, and surgeon experience influenced surgical time. Conversion rate increased with increasing body condition score and lesion size. Risk of death prior to discharge increased with increasing lesion size. Risk of conversion and death prior to discharge were lower when performed by more experienced surgeons. Capsular penetration during LA increased the risk of tumor recurrence. CLINICAL RELEVANCE: LA for resection of unilateral adrenal masses is associated with excellent outcomes in experienced centers. Surgeons with greater experience with LA have lower surgical times, conversion rates, and risk of death prior to discharge

Nebulized Recombinant Tissue Plasminogen Activator (rt-PA) for Acute COVID-19-Induced Respiratory Failure : An Exploratory Proof-of-Concept Trial

Acknowledgments We would like to extend our sincerest gratitude to all the colleagues and hospital staff who worked tirelessly throughout the pandemic and without whom this work would not have been possible. Firstly, we would like to thank our colleagues in the intensive care unit (ICU), in particular the matrons, Sean Carroll and Sinead Hanton, and research nurses, Filipe Helder and Amitaa Maharajh for their support, and bedside nurses who bore the responsibility of drug administration. We would also like to extend our thanks to ICU consultants who acted as professional legal consultees on behalf of critical care patients. Equally, we would like to thank colleagues within the respiratory team. Their expertise was instrumental to our role in treating patients on 8N and 8E wards. A special mention to lead Nurse Mary Emerson; we were grateful for her knowledge, support and for facilitating the training for the nebulizer and drug administration on the wards. We would like to thank Aarti Nandani and all the staff in the Royal Free clinical trials pharmacy for their immense support throughout the whole pandemic, especially considering their ever-increasing workload at the time. Thanks also to the HSL coagulation laboratory, the Trust R&D department and all the staff working to cover during a very challenging time. We are also very grateful to the Royal Free charity for funding this study. Finally, we would like to thank all the clinical nurses, physiotherapists, research data managers and healthcare professionals within the Haemophilia department (and wider hospital) for all their many efforts in supporting this study. This trial was overseen by an independent data monitoring committee, chaired by Najib Rahman, Director of the Oxford Respiratory Trials Unit, University of Oxford and comprises the following committee members: Mike Makris, Jonathan Silversides and Henry Watson. Funding Royal Free Charity Trust Fund 35 provided funding for this study. The study drug was provided by Boehringer Ingelheim (BI). BI had no role in the design, analysis, or interpretation of the results. They were given the opportunity to review the manuscript for medical and scientific accuracy since it relates to BI substances and intellectual property considerations.Peer reviewedPublisher PD