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Chest Feb 2024No studies have reported therapies for the treatment of patients with refractory Mycobacterium abscessus pulmonary disease (MAB-PD). We implemented intermittent...
BACKGROUND
No studies have reported therapies for the treatment of patients with refractory Mycobacterium abscessus pulmonary disease (MAB-PD). We implemented intermittent multidrug IV therapy (IMIT) through repeated hospitalizations for patients with MAB-PD who were refractory to antibiotics for more than 12 months.
RESEARCH QUESTION
What are the effects of IMIT on patients with refractory MAB-PD?
STUDY DESIGN AND METHODS
The IV antibiotics administered for IMIT included amikacin, imipenem, and tigecycline, and the outcomes for 36 patients who underwent IMIT for refractory MAB-PD were evaluated. Patients were repeatedly hospitalized and administered IMIT on recurrent symptoms or radiographic evidence of deterioration, while maintaining oral/inhaled antibiotics.
RESULTS
Of the 36 patients, 26 (72%) had M abscessus subspecies abscessus (herein, M abscessus)-PD, and 10 (28%) had M abscessus subspecies massiliense (herein, M massiliense)-PD. The median number of hospitalizations for IMIT was two (interquartile range, 1-3) for patients with M abscessus-PD and one (interquartile range, 1-2) for patients with M massiliense-PD. At least one negative culture result and culture conversion were observed in 62% and 12% of patients with M abscessus-PD, and in 80% and 60% of patients with M massiliense-PD, respectively. Symptomatic improvement was observed in all patients, and radiologic improvement, including cavity amelioration or no deterioration, was observed in 42% and 70% of patients with M abscessus-PD and with M massiliense-PD, respectively. No resistance to clarithromycin or amikacin was acquired.
INTERPRETATION
IMIT with intermittent hospitalization can be a beneficial palliative treatment for patients with refractory MAB-PD. This therapy alleviated symptoms, slowed radiologic progression, and reduced the bacterial burden in some patients. However, radiologic and microbiological responses to IMIT were more apparent in M massiliense-PD than in M abscessus-PD.
Topics: Humans; Mycobacterium abscessus; Amikacin; Mycobacterium Infections, Nontuberculous; Anti-Bacterial Agents; Clarithromycin; Lung Diseases; Microbial Sensitivity Tests
PubMed: 37661004
DOI: 10.1016/j.chest.2023.08.025 -
British Journal of Clinical Pharmacology Mar 2021Bayesian forecasting software can assist in guiding therapeutic drug monitoring (TDM)-based dose adjustments for amikacin to achieve therapeutic targets. This study...
AIMS
Bayesian forecasting software can assist in guiding therapeutic drug monitoring (TDM)-based dose adjustments for amikacin to achieve therapeutic targets. This study aimed to evaluate amikacin prescribing and TDM practices, and to determine the suitability of the amikacin model incorporated into the DoseMeRx® software as a replacement for the previously available software (Abbottbase®).
METHODS
Patient demographics, pathology, amikacin dosing history, amikacin concentrations and Abbottbase® predicted TDM targets (area under the curve up to 24 hours, maximum concentration and trough concentration) were collected for adults receiving intravenous amikacin (2012-2017). Concordance with the Australian Therapeutic Guidelines was assessed. Observed and predicted amikacin concentrations were compared to determine the predictive performance (bias and precision) of DoseMeRx®. Amikacin TDM targets were predicted by DoseMeRx® and compared to those predicted by Abbottbase®.
RESULTS
Overall, guideline compliance for 63 courses of amikacin in 47 patients was suboptimal. Doses were often lower than recommended. For therapy >48 h, TDM sample collection timing was commonly discordant with recommendations, therapeutic target attainment low and 34% of dose adjustments inappropriate. DoseMeRx® under-predicted amikacin concentrations by 0.9 mg/L (95% confidence interval [CI] -1.4 to -0.5) compared with observed concentrations. However, maximum concentration values (n = 19) were unbiased (-1.7 mg/L 95%CI -5.8 to 0.8) and precise (8.6% 95%CI 5.4-18.1). Predicted trough concentration values (n = 7) were, at most, 1 mg/L higher than observed. Amikacin area under the curve values estimated using Abbottbase® (181 mg h/L 95%CI 161-202) and DoseMeRx® (176 mg h/L 95%CI 152-199) were similar (P = .59).
CONCLUSION
Amikacin dosing and TDM practice was suboptimal compared with guidelines. The model implemented by DoseMeRx® is satisfactory to guide amikacin dosing.
Topics: Adult; Amikacin; Anti-Bacterial Agents; Australia; Bayes Theorem; Drug Monitoring; Humans; Software
PubMed: 32881037
DOI: 10.1111/bcp.14542 -
Microbiology Spectrum Jun 2023In view of the current increase and spread of antimicrobial resistance (AMR), there is an urgent need to find new strategies to combat it. This study had two aims....
In view of the current increase and spread of antimicrobial resistance (AMR), there is an urgent need to find new strategies to combat it. This study had two aims. First, we synthesized highly monodispersed silver nanoparticles (AgNPs) of approximately 17 nm, and we functionalized them with mercaptopoly(ethylene glycol) carboxylic acid (mPEG-COOH) and amikacin (AK). Second, we evaluated the antibacterial activity of this treatment (AgNPs_mPEG_AK) alone and in combination with hyperthermia against planktonic and biofilm-growing strains. AgNPs, AgNPs_mPEG, and AgNPs_mPEG_AK were characterized using a suite of spectroscopy and microscopy methods. Susceptibility to these treatments and AK was determined after 24 h and over time against 12 clinical multidrug-resistant (MDR)/extensively drug-resistant (XDR) isolates of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The efficacy of the treatments alone and in combination with hyperthermia (1, 2, and 3 pulses at 41°C to 42°C for 15 min) was tested against the same planktonic strains using quantitative culture and against one P. aeruginosa strain growing on silicone disks using confocal laser scanning microscopy. The susceptibility studies showed that AgNPs_mPEG_AK was 10-fold more effective than AK alone, and bactericidal efficacy after 4, 8, 24, or 48 h was observed against 100% of the tested strains. The combination of AgNPs_mPEG_AK and hyperthermia eradicated 75% of the planktonic strains and exhibited significant reductions in biofilm formation by P. aeruginosa in comparison with the other treatments tested, except for AgNPs_mPEG_AK without hyperthermia. In conclusion, the combination of AgNPs_mPEG_AK and hyperthermia may be a promising therapy against MDR/XDR and biofilm-producing strains. Antimicrobial resistance (AMR) is one of the greatest public health challenges, accounting for 1.27 million deaths worldwide in 2019. Biofilms, a complex microbial community, directly contribute to increased AMR. Therefore, new strategies are urgently required to combat infections caused by AMR and biofilm-producing strains. Silver nanoparticles (AgNPs) exhibit antimicrobial activity and can be functionalized with antibiotics. Although AgNPs are very promising, their effectiveness in complex biological environments still falls below the concentrations at which AgNPs are stable in terms of aggregation. Thus, improving the antibacterial effectiveness of AgNPs by functionalizing them with antibiotics may be a significant change to consolidate AgNPs as an alternative to antibiotics. It has been reported that hyperthermia has a large effect on the growth of planktonic and biofilm-producing strains. Therefore, we propose a new strategy based on AgNPs functionalized with amikacin and combined with hyperthermia (41°C to 42°C) to treat AMR and biofilm-related infections.
Topics: Amikacin; Silver; Metal Nanoparticles; Anti-Bacterial Agents; Biofilms; Hyperthermia, Induced
PubMed: 37078875
DOI: 10.1128/spectrum.00280-23 -
The International Journal of Risk &... 2023Acinetobacter baumannii is a major cause of nosocomial infections and high mortality rates. Evaluation of risk factors for such resistant infections may aid surveillance... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acinetobacter baumannii is a major cause of nosocomial infections and high mortality rates. Evaluation of risk factors for such resistant infections may aid surveillance and diagnostic initiatives, as well as, can be crucial in early and appropriate antibiotic therapy.
OBJECTIVE
To identify the risk factors in patients with resistant A. baumannii infection with respect to controls.
METHODS
Prospective or retrospective cohort and case-control studies reporting the risk factors for resistant A. baumannii infection were collected through two data sources, MEDLINE/PubMed and OVID/Embase. Studies published in the English language were included while animal studies were excluded. The Newcastle-Ottawa Scale was used to assess the quality of studies. The odds ratio of developing antibiotic resistance in patients with A. baumannii infection was pooled using a random-effect model.
RESULTS
The results are based on 38 studies with 60878 participants (6394 cases and 54484 controls). A total of 28, 14, 25, and 11 risk factors were identified for multi-drug resistant (MDRAB), extensive-drug resistant (XDRAB), carbapenem-resistant (CRAB) and imipenem resistant A. baumannii infection (IRAB), respectively. In the MDRAB infection group, exposure to carbapenem (OR 5.51; 95% CI: 3.88-7.81) and tracheostomy (OR 5.01; 95% CI: 2.12-11.84) were identified with maximal pool odd's ratio. While previous use of amikacin (OR 4.94; 95% CI: 1.89-12.90) and exposure to carbapenem (OR 4.91; 95% CI: 2.65-9.10) were the foremost factors associated with developing CRAB infection. Further analysis revealed, mechanical ventilation (OR 7.21; 95% CI: 3.79-13.71) and ICU stay (OR 5.88; 95% CI: 3.27-10.57) as the most significant factors for XDRAB infection.
CONCLUSION
The exposure of carbapenem, amikacin (previous) and mechanical ventilation were the most significant risk factors for multidrug, extensive-drug, and carbapenem resistance in patients with A. baumannii infection respectively. These findings may guide to control and prevent resistant infections by identifying the patients at higher risk of developing resistance.
Topics: Humans; Acinetobacter baumannii; Retrospective Studies; Prospective Studies; Amikacin; Drug Resistance, Multiple, Bacterial; Acinetobacter Infections; Carbapenems; Cross Infection; Risk Factors
PubMed: 37154184
DOI: 10.3233/JRS-220037 -
Indian Journal of Medical Microbiology 2023The CLSI annual update of its M100 document is eagerly awaited every year. This year's update, the M100-Ed33, was published in February, and will significantly affect... (Review)
Review
BACKGROUND
The CLSI annual update of its M100 document is eagerly awaited every year. This year's update, the M100-Ed33, was published in February, and will significantly affect clinical practices.
OBJECTIVE
To highlight and explain the rationale of the changes and their clinical impact.
CONTENT
The major changes this year are mostly focused on PK/PD data, selective and cascade reporting of the antibiotics and therapy related comments. The CLSI has moved away from its classical grouping of antibiotics (A, B, U, O) to a tier-based approach (Tier 1, 2, 3, 4) which will aid in cascade reporting during an antibiotic susceptibility testing (AST). Rather than non-fastidious, fastidious and anaerobe grouping, the tables have been made organism specific. The aminoglycosides breakpoints have been changed for both Enterobacterales and Pseudomonas aeruginosa while for P. aeruginosa, the breakpoints of piperacillin - tazobactam (TZP) are also updated. These updates are mostly based on attainment of drug plasma level for bacterial stasis rather than bactericidal effect of the antibiotics. It is noteworthy, that these breakpoint changes are made, keeping in view that the aminoglycosides for all organisms should be used in combination therapy. For P. aeruginosa, gentamicin has been removed, while amikacin has been restricted for urinary isolates only.
Topics: Humans; Anti-Bacterial Agents; Amikacin; Pseudomonas aeruginosa; Piperacillin, Tazobactam Drug Combination; Microbial Sensitivity Tests
PubMed: 37945125
DOI: 10.1016/j.ijmmb.2023.100432 -
Veterinary Clinical Pathology Jun 2023Pseudothrombocytopenia may lead to the erroneous diagnosis of thrombocytopenia, resulting in unnecessary testing and treatment. The addition of exogenous substances to...
BACKGROUND
Pseudothrombocytopenia may lead to the erroneous diagnosis of thrombocytopenia, resulting in unnecessary testing and treatment. The addition of exogenous substances to blood samples prior to collection has been shown to mitigate platelet (PLT) clumps in blood samples. Postcollection additives aiming to disaggregate PLT clumps have been largely unexplored.
OBJECTIVES
We aimed to determine if the addition of amikacin to blood samples postcollection aids in the disaggregation of PLT clumps in cats and dogs.
METHODS
For this prospective study, EDTA-collected blood samples from 28 cats and 17 dogs were obtained from a hospital population at UC Davis Veterinary Medical Teaching Hospital. Samples had PLT clumps detected on blood smears and thrombocytopenia per analyzer count. Amikacin was added to samples postcollection, and an additional CBC was performed. Flow cytometry was performed to assess PLT-fibrinogen binding in amikacin-treated aliquots.
RESULTS
PLT-clumped samples treated with amikacin significantly increased PLT numbers by 134% and decreased mean platelet volume (MPV) values by 14% (P ≤ 0.0001) in cats, and increased PLT numbers by 32% (P = 0.04) and increased MPV values by 9% (P = 0.02) in dogs. Mean cell volume (MCV) slightly increased (<4%) for both species. No other CBC parameters were substantially affected by the addition of amikacin. Flow cytometry showed decreased PLT-fibrinogen binding in the majority of cats but was not significant (P > 0.05).
CONCLUSIONS
Adding amikacin to PLT-clumped blood samples postcollection may be a convenient solution for pseudothrombocytopenia in cats and dogs. Future studies are needed to elucidate the mechanism of amikacin and its effectiveness under different storage conditions. This is the first reported use of amikacin postcollection to disaggregate PLT clumps in blood samples from animals.
Topics: Cats; Dogs; Animals; Platelet Count; Amikacin; Edetic Acid; Prospective Studies; Thrombocytopenia; Fibrinogen; Cat Diseases; Dog Diseases
PubMed: 36849708
DOI: 10.1111/vcp.13203 -
Critical Care Medicine Jun 2019
Topics: Amikacin; Anti-Bacterial Agents; Fosfomycin; Humans; Pneumonia, Ventilator-Associated; Pseudomonas Infections; Pseudomonas aeruginosa
PubMed: 31095023
DOI: 10.1097/CCM.0000000000003751 -
Current Drug Delivery 2021Amikacin is an aminoglycoside antibiotic used for many gram-negative bacterial infections like infections in the urinary tract, infections in brain, lungs and abdomen....
BACKGROUND
Amikacin is an aminoglycoside antibiotic used for many gram-negative bacterial infections like infections in the urinary tract, infections in brain, lungs and abdomen. Electrochemical determination of amikacin is a challenge in electroanalysis because it shows no voltammetric peak at the surface of bare electrodes.
OBJECTIVE
In this approach, a very simple and easy method for indirect voltammetric determination of amikacin presented in real samples. Gold nanoparticles were electrodeposited at the surface of glassy carbon electrode in constant potential.
METHODS
The effect of several parameters such as time and potential of deposition, pH and scan rates on signal were studied. The cathodic peak current of Au decreased with increasing amikacin concentration. Quantitative analysis of amikacin was performed using differential pulse voltammetry by following cathodic peak current of gold ions.
RESULTS
Two dynamic linear ranges of 1.0 × 10-1.0 × 10 M and 5.0 × 10-1.0 × 10 M were obtained and limit of detection was estimated 3.0× 10 M.
CONCLUSION
The method was successfully determined amikacin in pharmaceutical preparation and human serum. The effect of several interference in determination of amikacin was also studied.
Topics: Amikacin; Electrochemical Techniques; Electrodes; Gold; Humans; Metal Nanoparticles; Oxidation-Reduction
PubMed: 32682378
DOI: 10.2174/1567201817666200719005919 -
Expert Opinion on Drug Metabolism &... Feb 2017For safe and effective use of antibacterial agents in neonates, specific knowledge on the pharmacokinetics (PK) and its covariates is needed. This necessitates a... (Review)
Review
For safe and effective use of antibacterial agents in neonates, specific knowledge on the pharmacokinetics (PK) and its covariates is needed. This necessitates a stepwise approach, including prospective validation. Areas covered: We describe our approach throughout almost two decades to improve amikacin exposure in neonates. A dosing regimen has been developed and validated using pharmacometrics, considering current weight, postnatal age, perinatal asphyxia, and ibuprofen use. This regimen has been developed based on clinical and therapeutic drug monitoring (TDM) data collected during routine care, and subsequently underwent prospective validation. A similar approach has been scheduled to quantify the impact of hypothermia. Besides plasma observations, datasets on deep compartment PK were also collected. Finally, the available literature on developmental toxicology (hearing, renal) of amikacin is summarized. Expert opinion: The amikacin model reflects a semi-physiological function for glomerular filtration. Consequently, this model can be used to develop dosing regimens for other aminoglycosides or to validate physiology-based pharmacokinetic models. Future studies should explore safety with incorporation of covariates like pharmacogenetics, biomarkers, and long-term outcomes. This includes a search for mechanisms of developmental toxicity. Following knowledge generation and grading the level of evidence in support of data, dissemination and implementation initiatives are needed.
Topics: Amikacin; Animals; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Monitoring; Glomerular Filtration Rate; Humans; Infant, Newborn; Models, Biological
PubMed: 27623706
DOI: 10.1080/17425255.2017.1234606 -
MSphere Aug 2018Heteroresistance is a phenomenon where a subpopulation of cells exhibits higher levels of antibiotic resistance than the general population. Analysis of tobramycin...
Heteroresistance is a phenomenon where a subpopulation of cells exhibits higher levels of antibiotic resistance than the general population. Analysis of tobramycin resistance in AB5075 using Etest strips demonstrated that colonies with increased resistance arose at high frequency within the zone of growth inhibition. The presence of a resistant subpopulation was confirmed by population analysis profiling (PAP). The tobramycin-resistant subpopulation was cross resistant to gentamicin but not amikacin. The increased tobramycin resistance phenotype was highly unstable, and cells reverted to a less resistant population at frequencies of 60 to 90% after growth on nonselective media. Furthermore, the frequency of the resistant subpopulation was not increased by preincubation with subinhibitory concentrations of tobramycin. The tobramycin-resistant subpopulation was shown to replicate during the course of antibiotic treatment, demonstrating that these were not persister cells. In AB5075, a large plasmid (p1AB5075) carries , a 2″-nucleotidyltransferase that confers resistance to both tobramycin and gentamicin but not amikacin. The gene is part of an integron and is carried adjacent to four additional resistance genes that are all flanked by copies of an integrase gene. In isolates with increased resistance, this region was highly amplified in a RecA-dependent manner. However, in a mutant, colonies with unstable tobramycin resistance arose by a mechanism that did not involve amplification of this region. These data indicate that tobramycin heteroresistance occurs by at least two mechanisms in , and future studies to determine its effect on patient outcomes are warranted. has become an important pathogen in hospitals worldwide, where the incidence of these infections has been increasing. infections have become exceedingly difficult to treat due to a rapid increase in the frequency of multidrug- and pan-resistant isolates. This has prompted the World Health Organization to list as the top priority for the research and development of new antibiotics. This study reports for the first time a detailed analysis of aminoglycoside heteroresistance in We define the mechanistic basis for heteroresistance, where the gene encoding an aminoglycoside adenylyltransferase becomes highly amplified in a RecA-dependent manner. Remarkably, this amplification of 20 to 40 copies occurs stochastically in 1/200 cells in the absence of antibiotic selection. In addition, we provide evidence for a second RecA-independent mechanism for aminoglycoside heteroresistance. This study reveals that aminoglycoside resistance in is far more complex than previously realized and has important implications for the use of aminoglycosides in treating infections.
Topics: Acinetobacter baumannii; Amikacin; Aminoglycosides; Anti-Bacterial Agents; Disk Diffusion Antimicrobial Tests; Drug Resistance, Bacterial; Gentamicins; Humans; Integrons; Nucleotidyltransferases; Plasmids; Tobramycin
PubMed: 30111627
DOI: 10.1128/mSphere.00271-18