Cefepime/tazobactam compared with other tazobactam combinations against problem Gram-negative bacteria

Mushtaq, Shazad; Garello, Paolo; Vickers, Anna; Woodford, Neil; Livermore, David M.

doi:10.1016/j.ijantimicag.2021.106318

Cited by 14 publications

(9 citation statements)

References 31 publications

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“…The observation of the prevalence of multi-drug resistance and virulence characteristics in farm isolates highlights the need to develop alternate field-deployable antibacterial strategies. Combination therapy, wherein more than one antibiotic, or antibiotic with effector molecules are combined, has been deployed for the clinical management of infectious diseases in animals and humans [49,50].…”

Section: Discussionmentioning

confidence: 99%

Nanoparticle-Enabled Combination Therapy Showed Superior Activity against Multi-Drug Resistant Bacterial Pathogens in Comparison to Free Drugs

et al. 2022

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The emergence of multidrug-resistant (MDR) bacterial pathogens in farm animals and their zoonotic spread is a concern to both animal agriculture and public health. Apart from antimicrobial resistance (AMR), bacterial pathogens from the genera of Salmonella and Staphylococcus take refuge inside host cells, thereby demanding intervention strategies that can eliminate intracellular MDR pathogens. In this study, seven clinical isolates of Salmonella and Staphylococcus from swine farms were characterized for antibiotic (n = 24) resistance, resistance mechanisms, and virulence characteristics. All isolates showed resistance to one or more antibiotics and S. enterica ser. Typhimurium isolate had the highest resistance to the panel of antibiotics tested. Major resistance mechanisms identified were efflux pump and beta-lactamase enzyme activities. Staphylococcus isolates showed complete hemolysis and strong biofilm formation, while Salmonella isolates caused partial hemolysis, but showed no or weak biofilm formation. MDR isolates of S. aureus M12 and S. enterica ser. Typhimurium bacteria were subsequently tested against combinations of antibiotics and potentiating adjuvants for improved antibacterial efficacy using a checkerboard assay, and their fractional inhibitory concentration index (FICI) was calculated. A combination of chitosan and silica nanoparticles containing tetracycline (TET) and efflux pump inhibitor chlorpromazine (CPZ), respectively, was characterized for physicochemical properties and effectiveness against MDR Salmonella enterica ser. Typhimurium isolate. This combination of nano-encapsulated drugs improved the antibacterial efficacy by inhibiting AMR mechanisms (efflux activity, beta-lactamase enzyme activity, and hydrogen sulfide (H2S) production) and reducing intracellular pathogen load by 83.02 ± 14.35%. In conclusion, this study sheds light on the promising applicability of nanoparticle-enabled combination therapy to combat multidrug-resistant pathogens encountered in animal agriculture.

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Section: Discussionmentioning

confidence: 99%

Nanoparticle-Enabled Combination Therapy Showed Superior Activity against Multi-Drug Resistant Bacterial Pathogens in Comparison to Free Drugs

et al. 2022

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“…The test panel comprised around half of the Enterobacterales submitted to the UKHSA Antimicrobial Resistance and Healthcare-Associated Infections (AMRHAI) Reference Unit from July 2015 to July 2016. This collection, also including non-fermenters, was used for similar assessments of cefepime/tazobactam 8 and cefepime/zidebactam, 9 and comprises around half the set used for earlier assessments of ceftolozane/tazobactam 10 and ceftazidime/avibactam. 11 Most were referred owing to unusual resistance, particularly to carbapenems.…”

Section: Methodsmentioning

confidence: 99%

Activity of ertapenem/zidebactam (WCK 6777) against problem Enterobacterales

Mushtaq¹,

Garello²,

Vickers³

et al. 2022

Journal of Antimicrobial Chemotherapy

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Background Secondary healthcare will remain pressured for some years, both because SARS-CoV-2 will circulate as a nosocomial pathogen, and owing to backlogs of patients awaiting delayed elective procedures. These stresses will drive the use of Outpatient Parenteral Antibiotic Therapy (OPAT), which will need to cover increasingly resistant Gram-negative opportunists. We evaluated the activity of ertapenem/zidebactam, proposed for 2 + 2 g q24h administration. Materials and methods MICs were determined, by BSAC agar dilution, for 1632 Enterobacterales submitted to the UK national reference laboratory for investigation of antimicrobial resistance. Results Over 90% of Escherichia coli with AmpC, ESBLs, KPC, metallo- or OXA-48 carbapenemases were inhibited by ertapenem/zidebactam 1:1 at ertapenem’s current 0.5 mg/L breakpoint. For other major Enterobacterales, the proportions inhibited by ertapenem/zidebactam 1:1 at 0.5 mg/L were mostly 65% to 90% but were lower for Klebsiella pneumoniae/oxytoca with metallo- or OXA-48 β-lactamases. However, animal studies support an 8 mg/L breakpoint for ertapenem/zidebactam, based on a shortened T>MIC being needed compared with ertapenem alone. On this basis ertapenem/zidebactam would count as active against 90%–100% of isolates in all groups except K. pneumoniae/oxytoca with MBLs (±OXA-48), where MICs and percent susceptibility vary substantially even with inocula within the BSAC acceptable range. Conclusions Ertapenem/zidebactam has a proposed once-daily regimen well suited to OPAT. Even on highly conservative breakpoint projections, it has potential against MDR E. coli, including metallo-carbapenemase producers. If trial data sustain the 8 mg/L breakpoint indicated by animal experiments, its potential will extend widely across infections due to ESBL-, AmpC- and carbapenemase-producing Enterobacterales.

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“…Microrganismos desses grupos são caracterizados pela produção de AmpClactamases, o que leva a resistência de antimicrobianos da classe das cefalosporinas e na maioria das vezes, da classe das penicilinas(40).De acordo com Livermore et al(41), a combinação da cefepima com tazobactam poderia proteger a estrutura química das oximinocefalosporinas contra β-lactamases de espectro estendido. Desse modo, essa combinação resultou em resultados iniciais positivos em registros de casos de infecção no trato urinário com ou sem evolução para patologia no trato geniturinário na Índia.Um estudo recente mostra que a combinação da cefepima com inibidor de β-lactamase, tazobactam, pode ser eficaz tratar KPC resistente a ceftazidima(42). Pesquisas in vitro demonstram que a atividade da cefepime-tazobactam no caldo Mueller Hinton cátion ajustado com cloreto de sódio (NaCl) a 0,85%, que simula melhor as condições fisiológicas, teve aumento da atividade antimicrobiana contra K. pneumoniae portadores de blaKPC.Enquanto apresentaram uma atividade mais limitada contra isolados portadores de blaKPC quando utilizado o caldo MuellerHinton padrão(43).Seguindo Joshi et al(44), a combinação da cefepima com zidebactam é um tratamento em desenvolvimento clínico para tratar infecções bacterianas por Gram-negativos multirresistentes graves (MDR).…”

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Tratamento de infecções hospitalares causadas pela Klebsiella pneumoniae produtora de carbapenemase (KPC) com antibióticos da classe das cefalosporinas

Murai

Oyama

Cabrera

et al. 2022

Rev. Bras. Ciênc. Biomed.

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A Klebsiella pneumoniae é um bacilo Gram-negativo pertencente ao grupo das enterobactérias e pode ser encontrada na microbiota do trato gastrointestinal de indivíduos imunocompetentes. É uma importante causa de infecções hospitalares, principalmente em crianças, idosos e indivíduos imunossuprimidos; infecções do trato urinário e septicemias são as mais comuns. Cepas de Klebsiella pneumoniae produtora de carbapenemase (KPC), enzima capaz de decompor antibióticos da classe carbapenêmicos, penicilinas e cefalosporinas, foram identificadas pela primeira vez em 1996, nos Estados Unidos. A KPC é um patógeno de grande importância que vem trazendo enorme preocupação para saúde pública mundial, visto que as opções de antibioticoterapia são limitadas. A terapêutica baseia-se principalmente no uso de Polimixina B e Polimixina E, embora antibióticos da classe das cefalosporinas também possam ser utilizados. Considerando os dados acima descritos, o presente estudo teve como finalidade compilar e discutir trabalhos relacionados à Klebsiella pneumoniae produtora de carbapenemase (KPC), determinando os seus principais mecanismos de resistência aos diversos antibióticos da classe cefalosporinas. Além disso, discutimos alternativas de tratamento para infecções causadas por esse patógeno de forma a demonstrar a importância do tratamento correto, monitoramento de pacientes acometidos e alertar sobre os riscos da superresistência da KPC à saúde mundial. De acordo com os resultados obtidos, pudemos verificar que alguns antibióticos da classe das cefalosporinas possuem uma boa eficácia antimicrobiana contra a KPC multirresistente, mas são necessários mais estudos para determinar a atividade desses medicamentos na prática clínica. Portanto, é importante prevenir a disseminação de bactérias resistentes em ambiente hospitalar por meio de culturas de vigilância, controle e uso correto de antimicrobianos de uso restrito e por fim, manter bons hábitos de higiene e limpeza.

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Cefepime/tazobactam compared with other tazobactam combinations against problem Gram-negative bacteria

Cited by 14 publications

References 31 publications

Nanoparticle-Enabled Combination Therapy Showed Superior Activity against Multi-Drug Resistant Bacterial Pathogens in Comparison to Free Drugs

Nanoparticle-Enabled Combination Therapy Showed Superior Activity against Multi-Drug Resistant Bacterial Pathogens in Comparison to Free Drugs

Activity of ertapenem/zidebactam (WCK 6777) against problem Enterobacterales

Tratamento de infecções hospitalares causadas pela Klebsiella pneumoniae produtora de carbapenemase (KPC) com antibióticos da classe das cefalosporinas

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