Fosfomycin in severe infections due to genetically distinct pan-drug-resistant Gram-negative microorganisms: synergy with meropenem

Neto, Lauro Vieira Perdigão; Oliveira, Maura Salaroli de; Martins, Roberta Cristina Ruedas; Marchi, Ana Paula; Gaudereto, Juliana Januario; Costa, Lucianna Auxi Teixeira Josino da; Lima, Lia Fernandes Alves de; Takeda, Christianne Fernandes Valente; Costa, Sílvia Figueiredo; Levin, Anna S.

doi:10.1093/jac/dky406

Cited by 30 publications

(20 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Eravacycline is more potent compared to tigecycline and may be active against some tigecycline-resistant strains (especially considering the current EUCAST susceptibility breakpoint for tigecycline) [ 91 , 92 ]. Successful use of fosfomycin against extensively drug-resistant K. pneumoniae has been reported in small case series, often in combination with other antimicrobials [ 93 , 94 ]. Despite concerns about development of resistance during treatment, this does not appear to be a problem in clinical practice possibly because fosfomycin resistance may carry a biological fitness cost [ 95 , 96 ].…”

Section: Options For Capt-resistant K Pneumoniaementioning

confidence: 99%

“…Finally, synergistic combinations, such as colistin-based combinations [ 97 , 98 ] or combination of fosfomycin with carbapenems [ 94 , 99 ], may prove useful last-resort options, but pharmacodynamic/pharmacokinetic (PK/PD) and clinical studies are lacking, especially against isolates co-resistant to all components of the combinations [ 3 ]. Synergistic combinations based on ceftazidime/avibactam (combined with fosfomycin + aztreonam or meropenem) have also been reported for the treatment of ceftazidime/avibactam-resistant strains [ 26 ].…”

Section: Options For Capt-resistant K Pneumoniaementioning

confidence: 99%

“…5 Plazomicin is active against 93% of KPC-producing, 42% of MBL-producing (co-production of 16S-rRNA-methyltransferases), 87% of OXA-producing, and 95% of carbapenemase-negative carbapenem-resistant Enterobacterales [ 10 ]. 6 Fosfomycin has been shown to be effective against XDR/PDR K. pneumoniae [ 93 , 94 ], but its activity is highly variable [ 96 ]. 7 Cefiderocol is stable against hydrolysis by all carbapenemases (including MBL) and its mechanism of bacterial cell entry is independent of porin channels and efflux pumps.…”

Section: Options For Capt-resistant K Pneumoniaementioning

confidence: 99%

See 2 more Smart Citations

Treatment options for K. pneumoniae, P. aeruginosa and A. baumannii co-resistant to carbapenems, aminoglycosides, polymyxins and tigecycline: an approach based on the mechanisms of resistance to carbapenems

2020

View full text Add to dashboard Cite

The management of carbapenem-resistant infections is often based on polymyxins, tigecycline, aminoglycosides and their combinations. However, in a recent systematic review, we found that Gram-negative bacteria (GNB) co-resistant to carbapanems, aminoglycosides, polymyxins and tigecycline (CAPT-resistant) are increasingly being reported worldwide. Clinical data to guide the treatment of CAPT-resistant GNB are scarce and based exclusively on few case reports and small case series, but seem to indicate that appropriate (in vitro active) antimicrobial regimens, including newer antibiotics and synergistic combinations, may be associated with lower mortality. In this review, we consolidate the available literature to inform clinicians dealing with CAPT-resistant GNB about treatment options by considering the mechanisms of resistance to carbapenems. In combination with rapid diagnostic methods that allow fast detection of carbapenemase production, the approach proposed in this review may guide a timely and targeted treatment of patients with infections by CAPT-resistant GNB. Specifically, we focus on the three most problematic species, namely Klebsiella pneumoniae , Pseudomonas aeruginosa and Acinetobacter baumannii . Several treatment options are currently available for CAPT-resistant K. pneumonia . Newer β-lactam-β-lactamase combinations, including the combination of ceftazidime/avibactam with aztreonam against metallo-β-lactamase-producing isolates, appear to be more effective compared to combinations of older agents. Options for P. aeruginosa (especially metallo-β-lactamase-producing strains) and A. baumannii remain limited. Synergistic combination of older agents (e.g., polymyxin- or fosfomycin-based synergistic combinations) may represent a last resort option, but their use against CAPT-resistant GNB requires further study.

show abstract

Section: Options For Capt-resistant K Pneumoniaementioning

confidence: 99%

Section: Options For Capt-resistant K Pneumoniaementioning

confidence: 99%

Section: Options For Capt-resistant K Pneumoniaementioning

confidence: 99%

See 1 more Smart Citation

Treatment options for K. pneumoniae, P. aeruginosa and A. baumannii co-resistant to carbapenems, aminoglycosides, polymyxins and tigecycline: an approach based on the mechanisms of resistance to carbapenems

2020

View full text Add to dashboard Cite

show abstract

“…Among the agents commented on in this review, tigecycline and eravacycline do not exhibit relevant activity against P. aeruginosa. Although the extended infusion of a high dose of carbapenems combined with a second active antibiotic may be considered for the treatment of CR P. aeruginosa infections (2,(142)(143)(144), less is known about CR P. aeruginosa than about CRE, making this option less attractive.…”

Section: Carbapenem-resistant Organismsmentioning

confidence: 99%

Carbapenem-Resistant Gram-Negative Bacterial Infections in Children

Aguilera‐Alonso

Escosa-García

Saavedra-Lozano

et al. 2020

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Carbapenem-resistant organisms (CRO) are a major global public health threat. Enterobacterales hydrolyze almost all β-lactams through carbapenemase production. Infections caused by CRO are challenging to treat due to the limited number of antimicrobial options. This leads to significant morbidity and mortality. Over the last few years, several new antibiotics effective against CRO have been approved. Some of them (e.g., plazomicin or imipenem-cilastatin-relebactam) are currently approved for use only by adults; others (e.g., ceftazidime-avibactam) have recently been approved for use by children. Recommendations for antibiotic therapy of CRO infections in pediatric patients are based on evidence mainly from adult studies. The availability of pediatric pharmacokinetic and safety data is the cornerstone to broaden the use of proposed agents in adults to the pediatric population. This article provides a comprehensive review of the current knowledge regarding infections caused by CRO with a focus on children, which includes epidemiology, risk factors, outcomes, and antimicrobial therapy management, with particular attention being given to new antibiotics.

show abstract

“…Padrões de mutação da ompF: Q55K,A87S,V185I,N215S,L222D,R223L,N225T,E226A,R227K,D229K,F260Y,G262E,G263S,N264D,T266S,N267_G277del,F278I,S280D,N310D,N312T,V313A,P314H,V316A,S318G,Q320A,D351K,D353E,K356E,T358N,G359K,D364N,L311_N312_insAGR,V316_G317_insRFD; Padrão 2: K47D, D48N, N51D, S84A, L172V, Q179E, G182S, D184A, V185L, I195L, N215D, K221Q, L222Y, N225T, E226A, R227E, F260Y, G262E, G263A, N264D, F265N, N267_G277del, F278I, S280N, V313A, P314T, G315F, V316T, S318G, Q320A, D353E, T358N, I360V, I365T PINTO et al, 2014;MARGARETE et al, 2015;CAYÔ et al, 2017). O único outro gene decodificador de carbapenemase encontrado foi blaNDM-1, caso já publicado por Perdigão e colaboradores (PERDIGÃO NETO et al, 2019 diferença esperada e ainda em discussão na literatura (BESSER et al, 2018;BOGATY et al, 2018;TOLAR et al, 2019). Pelos resultados do PFGE, diríamos que se trata de um surto poli clonal; outras publicações já mostraram surtos poli clonais de Serratia (DAMJANOVIC et al, 2005).…”

Section: Padrões De Mutação Da Ompcunclassified

Serratia marcescens resistente a carbapenêmicos: epidemiologia, avaliação genotípica e fenotípica

Melo¹

View full text Add to dashboard Cite

Melo GVBP. Carbapenemic resistant Serratia marcescens: epidemiology, genotypic and phenotypic evaluation [thesis]. São Paulo: "Faculdade de Medicina, Universidade de São Paulo"; 2019. Serratia marcescens is an opportunistic agent, most often associated with nosocomial infection. It has high adaptability to the environment and ability to acquire antimicrobial resistance. This study is a retrospective cohort of patients colonized or infected with carbapenem-resistant Serratia marcescens (CrSm) between 2010 and 2013, admitted to the Instituto Central do Hospital das Clínicas de São Paulo (ICHC-FMUSP). Epidemiological data were collected through medical records and we analysed the isolates available in a strain bank. Risk factors for infection and sensitivity profile for broth microdilution were evaluated. We also investigated resistance mechanisms through PCR, PFGE and Whole Genome Sequencing.Sixty-three patients were included, 43 colonized and 20 with infection, including 12 from the bloodstream. Polymyxin use, renal failure, and catheter use within 30 days prior to isolation of CrSm and haematopoietic stem cell transplantation were correlated with infection in the univariate analysis and polymyxin use was the only one that remained in the analysis. multivariate. Forty-two isolates were analyzed from 35 patients and 3 environmental samples. MIC testing revealed 4 carbapenem-sensitive isolates, 42% sensitivity to amikacin and 27% sensitivity to tigecycline. Twenty-five of the 42 isolates carried blaKPC-2, which was the most frequent carbapenemase. An isolate carried blaNDM. The result of the PFGE indicates that there is a predominant clone, to which 71% of the isolates belong.We conclude that the LISTA DE ABREVIATURAS E SIGLAS A/S2 Ampicillin/Sulbactam AMI Amicacina AVC Acidente vascular cerebral AVCI Acidente vascular cerebral isquêmico AZT Aztreonam BCP Broncopneumonia BHI Brain Heart Infusion BHR Broad host ranges CI Cateter implantável CIM Concentração inibitória mínima

show abstract

Fosfomycin in severe infections due to genetically distinct pan-drug-resistant Gram-negative microorganisms: synergy with meropenem

Cited by 30 publications

References 18 publications

Treatment options for K. pneumoniae, P. aeruginosa and A. baumannii co-resistant to carbapenems, aminoglycosides, polymyxins and tigecycline: an approach based on the mechanisms of resistance to carbapenems

Treatment options for K. pneumoniae, P. aeruginosa and A. baumannii co-resistant to carbapenems, aminoglycosides, polymyxins and tigecycline: an approach based on the mechanisms of resistance to carbapenems

Carbapenem-Resistant Gram-Negative Bacterial Infections in Children

Serratia marcescens resistente a carbapenêmicos: epidemiologia, avaliação genotípica e fenotípica

Contact Info

Product

Resources

About