Contepo (IV fosfomycin) / Nabriva Therap, Nanjing King-Friend Bio - LARVOL DELTA

Meitheal Pharmaceuticals Receives Approval from the US Food and Drug Administration for CONTEPO (fosfomycin) for injection in Patients ≥ 18 Years Having Complicated Urinary Tract Infections (cUTI), Including Acute Pyelonephritis (AP) (FinancialContent) - "The FDA approval is supported by data from the pivotal Phase 2/3 ZEUS (ZTI-01) trial which investigated the safety and efficacy of the treatment on hospitalized patients with cUTI, including acute pyelonephritis."

FDA approval • Infectious Disease

PK Study of Single-Dose ZTI-01 in Children (<12 Years of Age) (clinicaltrials.gov) - P1 | N=21 | Recruiting | Sponsor: Nabriva Therapeutics AG | Trial completion date: Jan 2023 ➔ Jan 2026 | Trial primary completion date: Dec 2022 ➔ Dec 2025

Trial completion date • Trial primary completion date • Pediatrics

"any updates/word on CONTEPO from @nabriva ? last public update I saw was from 06/2020" (@minkeyw)

Improving Traditional Registrational Trial Endpoints: Development and Application of a Desirability of Outcome Ranking (DOOR) Endpoint for Complicated Urinary Tract Infection Clinical Trials. (PubMed, Clin Infect Dis) - "DOOR can effectively be utilized in registrational cUTI trials. The DOOR endpoint presented here can be adapted for other infectious diseases syndromes and prospectively incorporated into future clinical trials."

Journal • Infectious Disease • Nephrology

Pharmacodynamic and immunomodulatory effects of polymyxin B in combination with fosfomycin against KPC-2-producing Klebsiella pneumoniae. (PubMed, Int J Antimicrob Agents) - "The reduction in cytokine expression was greater with polymyxin B than fosfomycin alone, and combinations showed significantly greater reductions compared to monotherapies. Our findings suggest that further research is needed to understand immune-mediated killing to identify a strategy which harnesses the power of the immune response against these hard to treat bacteria in an in vivo system."

Combination therapy • Journal • PK/PD data • Immune Modulation • Infectious Disease • Inflammation • Pneumonia • CXCL8 • IL6 • TNFA

PK Study of Single-Dose ZTI-01 in Children (<12 Years of Age) (clinicaltrials.gov) - P1 | N=21 | Recruiting | Sponsor: Nabriva Therapeutics AG | Trial completion date: Jan 2022 ➔ Jan 2023 | Trial primary completion date: Dec 2021 ➔ Dec 2022

Trial completion date • Trial primary completion date • Pediatrics

[VIRTUAL] Epidemiology of Complicated Urinary Tract Infections (cUTIs) Presenting in Emergency Departments Across the United States (US) (IDWeek 2020) - "We examined rates of resistance to the following drugs/classes: 3rd generation cephalosporins, fluoroquinolones, trimethoprim-sulfamethoxazole, fosfomycin, and nitrofurantoin in patients presenting to the ED, stratified by those who were ultimately admitted as inpatients vs. not... Patients with cUTI infections presenting to EDs in the US are frequently resistant to many commonly used oral antibiotics, even in patients not admitted to the hospital. Local epidemiology and resistance should be considered when making empiric treatment decisions in the ED. New oral options for cUTI patients are needed to address the growing challenge of resistance."

Clinical • Infectious Disease

PK Study of Single-Dose ZTI-01 in Children (<12 Years of Age) (clinicaltrials.gov) - P1; N=21; Recruiting; Sponsor: Nabriva Therapeutics AG; Trial completion date: Jan 2021 ➔ Jan 2022; Trial primary completion date: Dec 2020 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Pediatrics

Synergistic antibacterial effects of colistin in combination with aminoglycoside, carbapenems, cephalosporins, fluoroquinolones, tetracyclines, fosfomycin, and piperacillin on multidrug resistant Klebsiella pneumoniae isolates. (PubMed, PLoS One) - "Colistin with either of gentamicin, meropenem, cefoperazone, cefotaxime, ceftazidime, moxifloxacin, minocycline, or piperacillin exhibited synergism against 81.82% (9 of 11 isolates). Combinations of colistin with either of tobramycin or ciprofloxacin showed synergism against 45.45% (5 in 11 isolates), while combinations of colistin with imipenem or ceftolozane and tazobactam displayed 36.36% (4 of 11 isolates) and 63.64% (7 of 11 isolates) synergism. In addition, combinations of colistin with levofloxacin was synergistic against 90.91% (10 of 11 isolates). The results revealed that combinations of colistin with other antibiotics could effectively inhibit colistin resistant isolates of K. pneumoniae, and thus could be further explore for the treatment of multidrug resistant pathogens."

Combination therapy • Journal • Infectious Disease • Pneumonia

[VIRTUAL] Neutropenic sepsis: can we do better? (BSH-I 2020) - "In these circumstances, our local current guidelines, based on the last audit in 2014, suggest the empiric use of piperacillin/tazobactam +/- gentamicin depending on the Multinational Association of Support in Cancer Care (MASCC) score and carbapenemase producing enterobacteriacea status...Analysis of antibiotic sensitivities revealed that gentamicin was the commonest sensitive antibiotic (59%), followed by fosfomycin (52·8%), amikacin (51·4%), imipenem (51·4%) and meropenem (50·7%)...In addition to this, where gram positive cocci are seen on gram stain or gram positive infections are highly likely, then the addition of vancomycin would be beneficial so as to cover Staphylococcus epidermidis...Table. Antibiotic Sensitivities of the Most Commonly Cultivated Organisms"

Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Septic Shock

Molecular profile of carbapenemase-producing Enterobacterales in burn patients. (PubMed, Tunis Med) - "The high prevalence of CPE in our center requires continued screening and reinforcement of hygiene measures."

Clinical • Journal • Infectious Disease • Mood Disorders • Pneumonia

Evaluation of BD Phoenix and Microscan WalkAway for determination of fosfomycin susceptibility in Staphylococcus aureus. (PubMed, Diagn Microbiol Infect Dis) - "Both methods exhibit ≤89.0% of categorica agreement and ≥63.3% of very major error. All commercial antimicrobial susceptibility systems show poor concordance with reference method."

Journal

External validation of INCREMENT-CPE score in a retrospective cohort of carbapenemase-producing Klebsiella pneumoniae bloodstream infections in critically ill patients. (PubMed, Clin Microbiol Infect) - "ICS showed similar predictive efficacy as compared to SAPS II, SOFA and Pitt bacteraemia scores."

Journal • Retrospective data • Critical care • Infectious Disease • Pneumonia

"Yes. Since we don't have caz avi and aztreonam in the country, nor cefiderocol, it's gent plus fosfomycin for severe NDM-1 pan R For pseudo, if it's carb R, cip r and pip tazo R, it's usually ceft-tazo R" (@DrToddLee)

"or an AppleWatch Crowbar...ProBar #SauceForMason...fosfomycin Carboplatin-resistant...carbapenem-resistant nbd, right?" (@minkeyw)

Genomic Features of MCR-1 and Extended-Spectrum β-Lactamase-Producing Enterobacterales from Retail Raw Chicken in Egypt. (PubMed, Microorganisms) - "Noteworthy, the fosA4 gene encoding resistance to fosfomycin was found in a single mcr-1-positive E. coli isolate, in which both genes were located on different conjugative plasmids...Whole-genome sequencing revealed three major types of mcr-1-bearing plasmids, corresponding to IncI2, IncX4, and IncHI2 scaffolds. The occurrence of MCR-1-producing multidrug-resistant Enterobacterales in retail raw chicken is of great concern, considering the possibility of transmission to humans through the food chain."

Journal

Emergence of mgrB locus deletion mediating polymyxin resistance in pandemic KPC-producing Klebsiella pneumoniae ST15 lineage. (PubMed, J Med Microbiol) - "Kp14U04 was resistant to most clinically useful antimicrobial agents, remaining susceptible only to aminoglycosides and fosfomycin...Additionally, Kp14U04 harboured a multiple stress resistance protein, efflux systems and regulators, heavy metal resistance and virulence genes, plasmids, prophage-related sequences and genomic islands. These features revealed the high potential of this isolate to resist antimicrobial therapy, survive in adverse environments, cause infections and overcome host defence mechanisms."

Journal • Complement-mediated Rare Disorders • Infectious Disease • Pneumonia

What's left in the cupboard? Older antimicrobials for treating gonorrhoea. (PubMed, J Antimicrob Chemother) - "Although unsuitable for empirical use, piperacillin/tazobactam, fosfomycin, co-trimoxazole, rifampicin and, possibly, chloramphenicol could be considered for individual patients with ceftriaxone-resistant gonococcal infection once MICs are known. Wider surveillance of the susceptibility of N. gonorrhoeae to these agents is needed, along with clinical trials and the establishment of clinical breakpoints for N gonorrhoeae."

Journal

Comprehensive genomic analysis reveals virulence factors and antibiotic resistance genes in Pantoea agglomerans KM1, a potential opportunistic pathogen. (PubMed, PLoS One) - "Further in-depth analysis showed that the genome contained 13 antibiotic resistance genes conferring resistance to clinically important antibiotics such as penicillin G, bacitracin, rifampicin, vancomycin, and fosfomycin. While production of TNF-α, IL-6 and NO involved solely activation of the NF-κB, IL-10 secretion was largely dependent on NF-κB and to a lesser extent on MAPK Kinases. Taken together, the analysis of the whole-genome and immunostimulatory properties provided in-depth characterization of the P. agglomerans KM1 isolate shedding a new light on determinants of virulence that drive its interactions with the environment, other microorganisms and eukaryotic hosts."

Journal • CNS Disorders • Immunology • Infectious Disease • Pneumonia • Respiratory Diseases • Rheumatology • IL10 • IL6 • TLR4 • TNFA

Antimicrobial Resistance of Non-O157 Shiga Toxin-Producing Escherichia coli Isolated from Humans and Domestic Animals. (PubMed, Antibiotics (Basel)) - "The highest resistance rate was to tetracycline (32.6%), followed by nalidixic acid (25.2%) and chloramphenicol and azithromycin (both 18.8%). However, imipenem and meropenem were effective against all isolates...A new fosfomycin-resistant gene, fosA7, was detected in strains from humans, cattle, and sheep...These results provide a reference to monitor the emergence and spread of multidrug resistant STEC strains among animals and humans. Furthermore, with a better understanding of antimicrobial genotypes and phenotypes among the diverse STEC strains obtained, this study could guide the administration of antimicrobial drugs in STEC infections when necessary."

Journal • Complement-mediated Rare Disorders

Global evolutionary epidemiology and resistome dynamics of Citrobacter species, Enterobacter hormaechei, Klebsiella variicola, and Proteeae clones. (PubMed, Environ Microbiol) - "Mcr-9 and other mcr variants were common in E. hormaechei subsp. and substantial in C. freundii whilst KPC, OXA-48, NDM, IMP, VIM, TEM, OXA and SHV were abundant in global E. hormaechei subsp., Citrobacter freundii, P. mirabilis, P. stuartii and P. rettgeri clones/clades; these resistance genes were mainly borne on IncF, IncX, IncN, IncH, Inc, IncM, A/C, and Col plasmids. Species-specific ampCs were highly conserved in respective species whilst fluoroquinolones, aminoglycosides, macrolides, fosfomycin, chloramphenicol, tetracycline, sulphamethoxazole and trimethoprim resistance mechanisms were abundantly enriched in almost all clades of most of the species, making them extensively and pandrug resistant; K. variicola, C. amalonaticus and C, koseri had relatively few resistance genes. Resistome similarities as well as local and international dissemination of strains evolving from common ancestors were observed, suggesting the anthroponotic, zoonotic, and food-/water-borne..."

Clinical • Journal

Validation of point-of-care device for rapid detection of urinary tract infection and antibiotic susceptibility (PubMed, Rev Chilena Infectol) - "The KAR® device could be a useful tool for diagnosing UTI in outpatients, especially in areas of low socio-economic level."

Clinical • Journal • Infectious Disease • Nephrology

Analysis of the Clinical Effect of Combined Drug Susceptibility to Guide Medication for Carbapenem-Resistant Klebsiella pneumoniae Patients Based on the Kirby-Bauer Disk Diffusion Method. (PubMed, Infect Drug Resist) - "In case of two-drug combinations, polymyxin+tigecycline, ceftazidime avibatan+tigecycline or (aztreonam, polymyxin B, fosfomycin), fosfomycin+polymycin, imipenem+tigecycline, and fosfomycin+tigecycline exhibited 100%, 87.5% (81.3%, 75.0%, 75.0%), 68.8%, 68.8%, and 62.5%, respectively, synergistic and/or cumulative antibacterial effects...The clinical efficacy results revealed that the combination of imipenem+tigecycline+fosfomycin showed the best results, followed by meropenem+fosfomycin, imipenem+tigecycline, ceftazidime avibatan, and ceftazidime+amikacin. The combined drug susceptibility results can facilitate guidance of the adjustment of antibacterial drug treatment regimens in patients with CRKP infection. For controlling the CRKP infection, it was found that treatment with carbapenems or ceftazidime avibatan demonstrated better antibacterial activity when combined with tigecycline and/or fosfomycin and/or polymyxin B."

Clinical • Journal • Critical care • Infectious Disease • Pneumonia

Mortality of Pandrug-Resistant Klebsiella pneumoniae Bloodstream Infections in Critically Ill Patients: A Retrospective Cohort of 115 Episodes. (PubMed, Antibiotics (Basel)) - "Mortality of PDR-Kp bloodstream infections was high. Administration of at least three antimicrobials might be beneficial for infections in critically ill patients caused by such pathogens."

Journal • Retrospective data • Critical care • Infectious Disease • Pneumonia • Septic Shock

Can fosfomycin be used for the treatment of Gram-negative urinary tract infections in children? (PubMed, Arch Dis Child) - No abstract available

Clinical • Journal • Infectious Disease • Nephrology