Review of therapeutic options for infections with carbapenem-resistant Klebsiella pneumoniae

Bandick, Rasmus; Mousavi, Soraya; Bereswill, Stefan; Heimesaat, Markus M.

doi:10.1556/1886.2020.00022

Cited by 10 publications

(3 citation statements)

References 44 publications

(69 reference statements)

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“…The combination of CAZ-AVI and aztreonam has already been reported as a promising treatment option against carbapenemase-producing pathogens, especially metallo-beta-lactamaseproducing gram-negative bacteria [39][40][41][42]. Polymyxins (polymyxin B and colistin) were addressed as the last resort antibiotics to treat CRKP infection before CAZ-AVI in clinical practice [1,[43][44][45]. However, a combination of CAZ-AVI and polymyxins has not been found in any clinical study.…”

Section: Discussionmentioning

confidence: 99%

Ceftazidime-Avibactam in Combination with In Vitro Non-susceptible Antimicrobials Versus Ceftazidime-Avibactam in Monotherapy in Critically Ill Patients with Carbapenem-Resistant Klebsiella Pneumoniae Infection: A Retrospective Cohort Study

Zheng

Zhang²,

Wang

et al. 2021

Infect Dis Ther

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Background: No clinical study has investigated the use of ceftazidime-avibactam combination schemes with an in vitro non-susceptible antimicrobial that could be superior to ceftazidime-avibactam monotherapy against carbapenem-resistant Klebsiella pneumoniae. Methods: We performed a retrospective cohort study at two tertiary hospitals in China for patients with carbapenem-resistant Klebsiella pneumoniae infection treated with ceftazidimeavibactam for at least 72 h. A Cox proportional hazards regression model was used to evaluate covariates that potentially affected 30-day mortality.Results: Sixty-two patients were eligible for our study; 41 (66.1%) received ceftazidime-avibactam combination therapy and 21 (33.9%) received ceftazidime-avibactam monotherapy. The overall 30-day mortality was 33.9% (21 patients): 24.4% (10/41) and 47.6% (11/21), P = 0.028, in combination and monotherapy groups, respectively. Combination therapy was Jianxin Zhang and Bei Wang are co-first author.

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Section: Discussionmentioning

confidence: 99%

Ceftazidime-Avibactam in Combination with In Vitro Non-susceptible Antimicrobials Versus Ceftazidime-Avibactam in Monotherapy in Critically Ill Patients with Carbapenem-Resistant Klebsiella Pneumoniae Infection: A Retrospective Cohort Study

Zheng

Zhang²,

Wang

et al. 2021

Infect Dis Ther

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“…Klebsiella pneumoniae can lead to pneumonia in hospitalized patients and people with weakened immune systems (Aris et al 2020 ) (Bandick et al 2020 ) (Marsot et al 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Amikacin-loaded niosome nanoparticles improve amikacin activity against antibiotic-resistant Klebsiella pneumoniae strains

Rahmati

Babapoor

Dezfulian

2022

World J Microbiol Biotechnol

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Amikacin is an aminoglycoside antibiotic used in drug-resistant bacterial infections. The spread of bacterial infections has become a severe concern for the treatment system because of the simultaneous drug resistance bacteria and SARS-CoV-2 hospitalized patients. One of the most common bacteria in the development of drug resistance is Klebsiella strains, which is a severe threat due to the possibility of biofilm production. In this regard, recent nanotechnology studies have proposed using nanocarriers as a practical proposal to improve the performance of antibiotics and combat drug resistance. Among drug nanocarriers, niosomes are considered for their absorption mechanism, drug coverage, and biocompatibility. In this study, niosomal formulations were synthesized by the thin-layer method. After optimizing the synthesized niosomes, their properties were evaluated in terms of stability and drug release rate. The toxicity of the optimal formulation was then analyzed. The effect of free amikacin and amikacin encapsulated in niosome on biofilm inhibition were compared in multi-drug resistant isolated Klebsiella strains, and the mrkD gene expression was calculated. The MIC and MBC were measured for the free drug and amikacin loaded in the noisome. The particle size of synthesized amikacin-loaded niosomes ranged from 175.2 to 248.3 nm. The results showed that the amount of lipid and the molar ratio of tween 60 to span 60 has a positive effect on particle size, while the molar ratio of surfactant to cholesterol has a negative effect. The highest release rate in amikacin-loaded niosomes is visible in the first 8 h, and then a slower release occurs up to 72 h. The cytotoxicity induced by amikacin-loaded niosome is significantly less than the cytotoxicity of free amikacin in HFF cells (*** p < 0.001, ** p < 0.01). The mrkD mRNA expression level in the studied strains was significantly reduced after treatment with niosome-containing amikacin compared to free amikacin (*** p < 0.001). It was confirmed that in the presence of the niosome, the amikacin antibacterial activity increased while the concentration of the drug used decreased, the formation of biofilm inhibited, and reduced antibiotics resistance in MDR Klebsiella strains.

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“…Combination of CAZ-AVI and aztreonam had been already reported as a promising treatment option against carbapenemase-producing pathogens, especially metallo-beta-lactamase-producing gram-negative bacteria [35][36][37][38]. Polymyxins (polymyxin B and colistin) were addressed as the last resort antibiotics to treat CRKP infection before CAZ-AVI coming into clinical practice [1,[39][40][41]. However, combination with CAZ-AVI and polymyxins was not found in any clinical studies.…”

Section: Discussionmentioning

confidence: 99%

Ceftazidime-avibactam in combination with in vitro non-susceptible antimicrobials versus ceftazidime-avibactam in monotherapy in critically ill patients with carbapenem-resistant Klebsiella pneumoniae infection

Zheng¹,

Zhang²,

Wang³

et al. 2021

Preprint

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Background: There is no clinical study investigating if using CAZ-AVI combination schemes with an in vitro non-susceptible antimicrobial could be superior to CAZ-AVI monotherapy against CRKP clinically. Methods: We performed a retrospective, cohort study at two tertiary hospitals in China for patients with CRKP infection who treated by CAZ-AVI at least 72 hours. A Cox-proportional hazards regression model was set up to evaluate covariates which potentially affected 30-day mortality. Results: Sixty-two patients were eligible in our study, 41 (66.1%) received CZA-AVI combination therapy and 21 (33.9%) received CZA-AVI monotherapy. The overall 30-day mortality was 33.9% (21 patients): 24.4% (10/41) and 47.6% (11/21), P=0.028, in combination and monotherapy groups, respectively. Combination therapy was significantly associated with lower 30-day mortality (HR 0.167, 95%CI 0.060-0.465, P=0.001), while higher APACHE II score, use of vasoactive drug and comorbidity of organ transplantation were considered as factors on increasing mortality. The propensity score showed no significant alteration with other variables after adding it into the final model. In the subgroup analysis, the protective effect revealed when combination with carbapenems, tigecycline or fosfomycin were applied, and in the following subgroups of patients: with sepsis, with CrCl > 50 mL/min, stayed in ICU ≤30 days or underwent mechanical ventilation. Conclusions: CAZ-AVI combination with another in vitro non-susceptible antimicrobial, especially carbapenems, fosfomycin and tigecycline, could significantly decrease 30-day mortality rate for critically ill patients with CRKP infection. Further investigation should be carried out to confirm this conclusion and find out the autofit antimicrobials in CAZ-AVI combination schemes.

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Review of therapeutic options for infections with carbapenem-resistant Klebsiella pneumoniae

Cited by 10 publications

References 44 publications

Ceftazidime-Avibactam in Combination with In Vitro Non-susceptible Antimicrobials Versus Ceftazidime-Avibactam in Monotherapy in Critically Ill Patients with Carbapenem-Resistant Klebsiella Pneumoniae Infection: A Retrospective Cohort Study

Ceftazidime-Avibactam in Combination with In Vitro Non-susceptible Antimicrobials Versus Ceftazidime-Avibactam in Monotherapy in Critically Ill Patients with Carbapenem-Resistant Klebsiella Pneumoniae Infection: A Retrospective Cohort Study

Amikacin-loaded niosome nanoparticles improve amikacin activity against antibiotic-resistant Klebsiella pneumoniae strains

Ceftazidime-avibactam in combination with in vitro non-susceptible antimicrobials versus ceftazidime-avibactam in monotherapy in critically ill patients with carbapenem-resistant Klebsiella pneumoniae infection

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