Polymyxin combination therapy for multidrug-resistant, extensively-drug resistant, and difficult-to-treat drug-resistant gram-negative infections: is it superior to polymyxin monotherapy?

Ardebili, Abdollah; Izanloo, Ahdieh; Rastegar, Mostafa

doi:10.1080/14787210.2023.2184346

Cited by 18 publications

(10 citation statements)

References 284 publications

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“…Colistin has become a crucial component in clinical practice, either as monotherapy or in combination therapy. 41 …”

Section: Discussionmentioning

confidence: 99%

Prevalence of Multidrug-Resistant Pathogens Causing Neonatal Early and Late Onset Sepsis, a Retrospective Study from the Tertiary Referral Children’s Hospital

Fang¹,

Gao²,

Yang³

et al. 2023

IDR

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Introduction Sepsis is the most severe infectious disease with the highest mortality rate, particularly among neonates admitted to the neonatal intensive care unit (NICU). This study retrospectively analyzed the epidemiology, antibiotic resistance profiles, and prevalence of multidrug-resistant (MDR) bacteria isolated from blood or cerebrospinal fluid (CSF) cultures in order to evaluate the appropriateness of initial empirical therapy for neonatal sepsis. Methods A retrospective study was conducted in the NICU from January 1, 2015, to December 31, 2022. Microbiological data from patients admitted to the NICU were anonymously extracted from the Laboratory of Microbiology database. Neonatal sepsis was classified into two types: early-onset sepsis (EOS), which occurs within the first 72 hours of life, and late-onset sepsis (LOS) for those begins later. Results A total of 679 bacterial strains, 543 from blood and 136 from CSF, were detected in 631 neonates. Among these, 378 isolates (55.67%) were Gram-positive bacteria, and 301 isolates (44.33%) were Gram-negative bacteria. The most frequently isolated pathogens were Coagulase-negative staphylococci (CoNS) (36.52%), followed by Klebsiella pneumoniae (20.47%) and Escherichia coli (13.84%). In EOS, 121 strains were found, CoNS represented the majority (33.88%), followed by Klebsiella pneumoniae (23.97%) and Escherichia coli (8.26%). Early-onset septicemia exhibited 67 (55.37%) MDR bacteria. In LOS, 558 strains were isolated, CoNS represented the majority of pathogens (37.10%), followed by Klebsiella pneumoniae (19.71%) and Escherichia coli (15.05%). Late-onset septicemia showed 332 (59.50%) MDR bacteria. High rates of MDR were found in CoNS (76.21%), carbapenem-resistant Klebsiella pneumoniae (66.91%), and MRSA (33.33%). Conclusion The study revealed an alarming prevalence of MDR strains isolated from neonatal sepsis, emphasizing the necessity of finding effective prevention and treatment measures. Colistin can be used for MDR Gram-negative bacteria, while vancomycin and teicoplanin can be considered treatment therapies for staphylococcal infections.

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“…Colistin has become a crucial component in clinical practice, either as monotherapy or in combination therapy. 41 …”

Section: Discussionmentioning

confidence: 99%

Prevalence of Multidrug-Resistant Pathogens Causing Neonatal Early and Late Onset Sepsis, a Retrospective Study from the Tertiary Referral Children’s Hospital

Fang¹,

Gao²,

Yang³

et al. 2023

IDR

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“…In recent years, application of AMPs in combination with conventional antibiotics has been shown to be effective against the biofilm structures as a viable therapeutic approach [ 15 , 41 , 50 , 51 ]. It also allows reducing the dosages, attenuating the rates of adverse events, and enhancing the selective toxicity of antibiotics [ 52 , 53 ]. Here, we examined the effects of combining the prototypical lantibiotic nisin and conventional antibiotic oxacillin on biofilm formation and/or eradication of S. aureus ATCC 43,300 and S. epidermidis clinical isolates.…”

Section: Discussionmentioning

confidence: 99%

Combination antimicrobial therapy: in vitro synergistic effect of anti-staphylococcal drug oxacillin with antimicrobial peptide nisin against Staphylococcus epidermidis clinical isolates and Staphylococcus aureus biofilms

Sharafi,

Ghaemi,

Rafiee

et al. 2024

Ann Clin Microbiol Antimicrob

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The ability of Staphylococcus epidermidis and S. aureus to form strong biofilm on plastic devices makes them the major pathogens associated with device-related infections (DRIs). Biofilm-embedded bacteria are more resistant to antibiotics, making biofilm infections very difficult to effectively treat. Here, we evaluate the in vitro activities of anti-staphylococcal drug oxacillin and antimicrobial peptide nisin, alone and in combination, against methicillin-resistant S. epidermidis (MRSE) clinical isolates and the methicillin-resistant S. aureus ATCC 43,300. The minimum inhibitory concentrations (MIC) and minimum biofilm eradication concentrations (MBEC) of oxacillin and nisin were determined using the microbroth dilution method. The anti-biofilm activities of oxacillin and nisin, alone or in combination, were evaluated. In addition, the effects of antimicrobial agents on the expression of icaA gene were examined by quantitative real-time PCR. MIC values for oxacillin and nisin ranged 4–8 µg/mL and 64–128 µg/mL, respectively. Oxacillin and nisin reduced biofilm biomass in all bacteria in a dose-dependent manner and this inhibitory effect was enhanced with combinatorial treatment. MBEC ranges for oxacillin and nisin were 2048–8192 µg/mL and 2048–4096 µg/mL, respectively. The addition of nisin significantly decreased the oxacillin MBECs from 8- to 32-fold in all bacteria. At the 1× MIC and 1/2× MIC, both oxacillin and nisin decreased significantly the expression of icaA gene in comparison with untreated control. When two antimicrobial agents were combined at 1/2× MIC concentration, the expression of icaA were significantly lower than when were used alone. Nisin/conventional oxacillin combination showed considerable anti-biofilm effects, including inhibition of biofilm formation, eradication of mature biofilm, and down-regulation of biofilm-related genes, proposing its applications for treating or preventing staphylococcal biofilm-associated infections, including device-related infections.

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“…The Infectious Diseases Society of America (IDSA) Guidance on the Treatment of Antimicrobial-Resistant Gram-negative Infections: Version 2.0 recommends "combination therapy with at least two active agents, whenever possible" for moderate to severe infections caused by carbapenemresistant A. baumannii [7]. While data on colistin-based combination regimens are limited in the treatment of infections caused by multidrug-resistant A. baumannii, debate and research continue as to which combinations are most effective [7,22,26,27].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of combination therapies with colistin in an experimental mouse pneumonia model induced by carbapenem‐resistant Acinetobacter baumannii strain

Ünal

Kaya

Öztürk

et al. 2023

Fundamemntal Clinical Pharma

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The treatment options are limited in Acinetobacter baumannii infections. In this study, the effectiveness of colistin monotherapy and combinations of colistin with different antibiotics were investigated in an experimental pneumonia model induced by carbapenem-resistant A. baumannii strain. Mice in the study were divided into five groups as control (no treatment), colistin monotherapy, colistin + sulbactam, colistin + imipenem, and colistin + tigecycline combinations. The modified experimental surgical pneumonia model of Esposito and Pennington was applied to all groups. The presence of bacteria in blood and lung samples was investigated. Results were compared. In blood cultures, while there was no difference between the control and colistin groups, there was a statistical difference between the control and the combination groups (P = 0.029). When the groups were compared in terms of lung tissue culture positivity, there was a statistical difference between the control group and all treatment groups (colistin, colistin + sulbactam, colistin + imipenem, and colistin + tigecycline) (P = 0.026, P < 0.001, P < 0.001, and P = 0.002, respectively). The number of microorganisms that grew in the lung tissue was found to be statistically significantly lower in all treatment groups in comparison with the control group (P = 0.001). Both monotherapy and combination therapies of colistin were found to be effective in the treatment of carbapenem-resistant A. baumannii pneumonia, but the superiority of combination therapies over colistin monotherapy has not been demonstrated.Acinetobacter baumannii is a substantial nosocomial infection agent in the world [1]. It can cause various lifethreatening infections, such as ventilator-associated pneumonia, bloodstream infection, urinary tract infection, meningitis, and wound infection [2]. The treatment of A. baumannii infections is difficult due to intrinsic and acquired antimicrobial resistance [3]. Treatment options are limited, and morbidity and mortality rates are high in the infections that develop with multidrug-resistant and pandrug-resistant strains of this microorganism. It constitutes a serious problem in infection control, especially in intensive care units [4]. Since carbapenems are stable against some beta-lactamase enzymes

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Polymyxin combination therapy for multidrug-resistant, extensively-drug resistant, and difficult-to-treat drug-resistant gram-negative infections: is it superior to polymyxin monotherapy?

Cited by 18 publications

References 284 publications

Prevalence of Multidrug-Resistant Pathogens Causing Neonatal Early and Late Onset Sepsis, a Retrospective Study from the Tertiary Referral Children’s Hospital

Prevalence of Multidrug-Resistant Pathogens Causing Neonatal Early and Late Onset Sepsis, a Retrospective Study from the Tertiary Referral Children’s Hospital

Combination antimicrobial therapy: in vitro synergistic effect of anti-staphylococcal drug oxacillin with antimicrobial peptide nisin against Staphylococcus epidermidis clinical isolates and Staphylococcus aureus biofilms

Evaluation of combination therapies with colistin in an experimental mouse pneumonia model induced by carbapenem‐resistant Acinetobacter baumannii strain

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