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British Journal of Clinical Pharmacology Jul 2023This study aimed to characterize the population pharmacokinetic parameters of intravenously administered amikacin in newborns and assess the effect of sepsis in amikacin...
AIMS
This study aimed to characterize the population pharmacokinetic parameters of intravenously administered amikacin in newborns and assess the effect of sepsis in amikacin exposure.
METHODS
Newborns aged ≥3 days who received at least 1 dose of amikacin during their hospitalization period were eligible for the study. Amikacin was administered intravenously during a 60-min infusion period. Three venous blood samples were taken from each patient during the first 48 h. Population pharmacokinetic parameter estimates were obtained using a population approach with the programme NONMEM.
RESULTS
Data from 329 drug assay samples were obtained from 116 newborn patients (postmenstrual age [PMA] 38.3, range 32-42.4 weeks; weight 2.8, range 1.6-3.8 kg). Measured amikacin concentrations ranged from 0.8 to 56.4 mg/L. A 2-compartment model with linear elimination produced a good fit of the data. Estimated parameters for a typical subject (2.8 kg, 38.3 weeks) were clearance (Cl = 0.16 L/h), intercompartmental clearance (Q = 0.15 L/h), volume of distribution of the central compartment (Vc = 0.98 L) and peripheral volume of distribution (Vp = 1.23 L). Total bodyweight, PMA and the presence of sepsis positively influenced Cl. Plasma creatinine concentration and circulatory instability (shock) negatively influenced Cl.
CONCLUSION
Our main results confirm previous findings showing that weight, PMA and renal function are relevant factors influencing newborn amikacin pharmacokinetics. In addition, current results showed that pathophysiological states of critically ill neonates, such as sepsis and shock, were associated with opposite effects in amikacin clearance and should be considered in dose adjustments.
Topics: Humans; Infant, Newborn; Amikacin; Anti-Bacterial Agents; Neonatal Sepsis; Sepsis; Metabolic Clearance Rate
PubMed: 36811146
DOI: 10.1111/bcp.15697 -
Internal Medicine (Tokyo, Japan) Aug 2022
Topics: Administration, Inhalation; Amikacin; Anti-Bacterial Agents; Humans; Liposomes; Microbial Sensitivity Tests; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Pneumonia
PubMed: 35110485
DOI: 10.2169/internalmedicine.8796-21 -
Veterinary Dermatology Feb 2022Anecdotally, amikacin has been added to compounded topical preparations for the management of canine bacterial otitis externa. However, the stability of amikacin within...
BACKGROUND
Anecdotally, amikacin has been added to compounded topical preparations for the management of canine bacterial otitis externa. However, the stability of amikacin within these solutions is unknown.
HYPOTHESIS/OBJECTIVES
The purpose of this study was to determine the stability of amikacin at 10 and 30 mg/mL concentrations in four topical solutions over a 56 day period. We hypothesised that amikacin would maintain chemical stability within the various solutions.
METHODS AND MATERIALS
Amikacin was formulated to 10 and 30 mg/mL (1% and 3%) concentrations within four topical solutions: tris-EDTA (TrizEDTA Aqueous Flush) (TE); 0.15% chlorhexidine gluconate and tris-EDTA (TrizCHLOR Flush) (TC); 0.9% NaCl (NA); and 0.9% NaCl + 2 mg/mL dexamethasone (ND). Samples were made in duplicate and stored at room temperature (25°C) for 0, 7,14, 21, 28 and 56 days. Amikacin content was quantified, in triplicate, by ultrahigh-performance liquid chromatography tandem mass spectrometry.
RESULTS
The recovered amikacin concentrations for the 10 mg/mL solutions ranged from 10 to 13.5 mg/mL (mean 11.5 mg/mL) with the exception of NA sample 2 at Day (D)0 (9.4 mg/mL) and D7 (9.2 mg/mL). The recovered amikacin concentrations for the 30 mg/mL solutions ranged from 30 to 40.2 mg/mL (mean 35.7 mg/mL). No significant difference was seen between the amikacin concentrations at D0 compared to D56 for all solutions except 10 mg/mL TE (P < 0.001).
CONCLUSIONS AND CLINICAL RELEVANCE
Amikacin maintained stability within TE, TC, NA and ND over 56 days except when formulated at 10 mg/mL within TE.
Topics: Amikacin; Animals; Chromatography, High Pressure Liquid; Dog Diseases; Dogs; Drug Stability; Otitis Externa; Solutions
PubMed: 34545642
DOI: 10.1111/vde.13025 -
Journal of Global Antimicrobial... Dec 2023Ceftazidime-avibactam (CAZ-AVI) combines ceftazidime and a reversible β-lactamase inhibitor that has shown activity against multidrug-resistant (MDR) Enterobacterales...
OBJECTIVES
Ceftazidime-avibactam (CAZ-AVI) combines ceftazidime and a reversible β-lactamase inhibitor that has shown activity against multidrug-resistant (MDR) Enterobacterales and P. aeruginosa. Using data from the Antimicrobial Testing Leadership and Surveillance program (ATLAS), this study examined the in vitro antimicrobial activity of CAZ-AVI and other antibiotics against Gram-negative bacteria collected from Chilean hospitals between 2015 and 2021.
METHODS
Clinical isolates of Enterobacterales and P. aeruginosa were collected from three medical centres in Chile. Blood, abdominal fluid, urine, soft tissues, and respiratory tract samples were obtained from infected patients. Minimum inhibitory concentrations using the broth microdilution method were determined for susceptibility testing, and the Clinical and Laboratory Standards Institute (CLSI) breakpoints were used for interpreting the results. Extended-spectrum β-lactamases (ESBL) and carbapenemase genes were also detected through polymerase chain reaction.
RESULTS
A total of 2600 Enterobacterales and 836 P. aeruginosa were analysed. CAZ-AVI was the antibiotic with the highest in vitro activity against Enterobacterales (99.72%). The incidence of carbapenem-resistant Enterobacterales (CRE) was 1.5% (n = 39), and the antibiotics with the best in vitro activity were tigecycline (92.31%), CAZ-AVI (88.57%), and amikacin (79.49%). CAZ-AVI was the antibiotic with the best activity against ESBL-producing Enterobacterales (99.34%) and MDR Enterobacterales (99.31%). For KPC-producing Enterobacterales, susceptibility to amikacin was 100%, whereas susceptibility to CAZ-AVI was 91.67%. Regarding MDR and difficult-to-treat resistance P. aeruginosa, 44.83% and 38.99% were susceptible to CAZ-AVI, respectively.
CONCLUSION
CAZ-AVI shows excellent in vitro activity against Enterobacterales in general, CRE, ESBL-producing Enterobacterales, and KPC-producing Enterobacterales. CAZ-AVI is also an option against MDR P. aeruginosa.
Topics: Humans; Ceftazidime; Chile; Amikacin; Anti-Bacterial Agents; Carbapenems; Pseudomonas aeruginosa
PubMed: 37714380
DOI: 10.1016/j.jgar.2023.09.004 -
Microbiology Spectrum Apr 2022Relebactam is a novel β-lactamase inhibitor of Ambler class A and C β-lactamases that has been developed in combination with imipenem/cilastatin for the treatment of...
Relebactam is a novel β-lactamase inhibitor of Ambler class A and C β-lactamases that has been developed in combination with imipenem/cilastatin for the treatment of carbapenem-resistant bacterial infections. In this study, we evaluated the antibacterial activity of imipenem/relebactam (IMR) against imipenem-nonsusceptible Enterobacterales and Pseudomonas aeruginosa isolates from Japan. Two sets of antibacterial susceptibility tests were conducted according to the susceptibility testing standard of the Clinical and Laboratory Standards Institute. In the first set, antibacterial susceptibility as measured by the MIC (MIC range) of IMR was assessed for the following 61 imipenem-nonsusceptible strains: 2 Enterobacter cloacae complex (not determined [0.25 μg/mL]), 33 Klebsiella aerogenes (0.5/1 μg/mL [0.5 to 1 μg/mL]), 2 Serratia marcescens (not determined [1 to 2 μg/mL]), and 24 P. aeruginosa (2/128 μg/mL [0.25 to >128 μg/mL]). In the second set, antibacterial susceptibility was assessed for the following 8 imipenem-nonsusceptible strains: 4 Escherichia coli, 1 E. cloacae complex and 3 Klebsiella pneumoniae. The MIC ranges of IMR for these strains were 0.25 to 0.5 μg/mL, 0.5 μg/mL, and 0.5 to 16 μg/mL, respectively. The antibacterial activity of IMR was similar to or lower than that of amikacin and comparable to or greater than those of other reference drugs. In conclusion, IMR has shown antibacterial activity against clinical isolates from Japan and, therefore, is expected to become a new therapeutic option for carbapenem-resistant infections in Japan. Carbapenem-resistant Enterobacterales and carbapenem-resistant Pseudomonas aeruginosa strains pose a global threat. Antibacterial activity of imipenem/relebactam (IMR) against clinical isolates of these bacteria from several global regions has been shown; however, as yet there are no reports on Japanese isolates. In this study, we evaluated the antibacterial activity of IMR against imipenem-nonsusceptible Enterobacterales and Pseudomonas aeruginosa isolates from Japan. The antibacterial activity of IMR against imipenem-nonsusceptible Enterobacterales was generally comparable to that of amikacin (AMK) and comparable to or higher than those of other reference drugs tested. The antibacterial activity of IMR against imipenem-nonsusceptible P. aeruginosa isolates was lower than that of AMK but comparable to or higher than those of other drugs. These results support the use of IMR as a new treatment option for infections due to Enterobacterales and P. aeruginosa strains that are resistant to existing β-lactams and other antibacterial agents.
Topics: Amikacin; Anti-Bacterial Agents; Azabicyclo Compounds; Carbapenems; Imipenem; Japan; Microbial Sensitivity Tests; Pseudomonas aeruginosa
PubMed: 35416695
DOI: 10.1128/spectrum.02235-21 -
Synergistic Effects of Omadacycline with Other Antimicrobial Agents against Mycobacterium abscessus.Antimicrobial Agents and Chemotherapy Jun 2023The clinical importance of Mycobacterium abscessus species (MABS) infections has been increasing. However, the standard treatment regimens recommended in the current...
The clinical importance of Mycobacterium abscessus species (MABS) infections has been increasing. However, the standard treatment regimens recommended in the current guidelines often result in unfavorable outcomes. Therefore, we investigated the activity of omadacycline (OMC), a novel tetracycline, against MABS to explore its potential as a novel therapeutic option. The drug susceptibilities of 40 Mycobacterium abscessus subsp. (Mab) clinical strains obtained from the sputum of 40 patients from January 2005 to May 2014 were investigated. The MIC results for OMC, amikacin (AMK), clarithromycin (CLR), clofazimine (CLO), imipenem (IPM), rifabutin (RFB), and tedizolid (TZD) alone and their combined effects (with OMC) were examined using the checkerboard method. Additionally, we studied the differences in the effectiveness of the antibiotic combinations based on the colony morphotype of Mab. The MIC and MIC of OMC alone were 2 and 4 μg/mL, respectively. The combinations of OMC with AMK, CLR, CLO, IPM, RFB, and TZD showed synergy against 17.5%, 75.8%, 25.0%, 21.1%, 76.9%, and 34.4% of the strains, respectively. Additionally, OMC combined with CLO (47.1% versus 9.5%, 0.023) or TZD (60.0% versus 12.5%, 0.009) showed significantly higher synergy against strains with rough morphotypes than those with smooth morphotypes. In conclusion, the checkerboard analyses revealed that the synergistic effects of OMC were observed most frequently with RFB, followed by CLR, TZD, CLO, IPM, and AMK. Furthermore, OMC tended to be more effective against rough-morphotype Mab strains.
Topics: Humans; Mycobacterium abscessus; Mycobacterium Infections, Nontuberculous; Anti-Bacterial Agents; Clarithromycin; Amikacin; Anti-Infective Agents; Mycobacterium; Rifabutin; Tetracyclines; Microbial Sensitivity Tests
PubMed: 37154742
DOI: 10.1128/aac.01579-22 -
Veterinary Clinical Pathology Mar 2022Physiologically, feline platelets are more reactive and prone to aggregation, which interferes with platelet counts using automated counters and manual methods. The use...
INTRODUCTION
Physiologically, feline platelets are more reactive and prone to aggregation, which interferes with platelet counts using automated counters and manual methods. The use of aminoglycoside amikacin in association with EDTA has proven to be efficient in preventing platelet aggregates in cases of pseudo thrombocytopenia (PTP) in people.
OBJECTIVES
This study evaluated the efficacy of amikacin in preventing platelet aggregation in EDTA-containing feline blood samples and investigated the possible effects on hematologic measurands.
MATERIALS AND METHODS
Blood samples (1.0 mL) collected from 100 healthy cats were stored in two EDTA tubes: 0.5 mL in a microtube containing 10 μL of 250 mg/mL amikacin (EDTA-AMK group) and 0.5 mL in a microtube containing only K2 EDTA 10% (EDTA group). A CBC was executed with an automated impedance blood analyzer, and a microscopic examination of the blood smears was performed.
RESULTS
Platelet clumps were observed in 56% of samples from the EDTA group and 5% of samples from the EDTA-AMK group. Platelet counts (PLT), plateletcrit (PCT), and WBC counts were significantly higher (P < .001) in the EDTA-AMK group compared withi the EDTA group.
CONCLUSIONS
Amikacin prevents platelet aggregation in feline venous blood samples and does not cause clinically relevant changes in other hematologic measurands. To our knowledge, this is the first report showing the use of amikacin in preventing platelet aggregation in feline blood samples. Based on this study, amikacin could be added to EDTA collection tubes for complete blood counts in cats.
Topics: Amikacin; Animals; Cat Diseases; Cats; Edetic Acid; Humans; Platelet Aggregation; Platelet Count; Thrombocytopenia
PubMed: 35141933
DOI: 10.1111/vcp.13074 -
The New England Journal of Medicine Feb 2024
Topics: Humans; Amikacin; Pneumonia, Ventilator-Associated; Anti-Bacterial Agents; Administration, Inhalation
PubMed: 38381690
DOI: 10.1056/NEJMc2400427 -
Brazilian Journal of Microbiology :... Dec 2021Infections by carbapenem-resistant Klebsiella pneumoniae (CRKp) are an increasing global threat with limited therapeutic options. Our objective was to evaluate clinical...
Infections by carbapenem-resistant Klebsiella pneumoniae (CRKp) are an increasing global threat with limited therapeutic options. Our objective was to evaluate clinical and microbiological outcomes of patients treated with amikacin for CRKp infections. We did a retrospective cohort of patients > 18 years old, with CRKp infections treated with amikacin in two tertiary care hospitals in Porto Alegre, Brazil. The impact of clinical factors, antibiotic treatment, and amikacin minimum inhibitory concentration (MIC) on patients' 30-day mortality was assessed. Microbiological clearance and nephrotoxicity (assessed by RIFLE score) were evaluated as secondary outcomes. A Cox regression analysis was done for mortality. We included 84 patients for analysis. Twenty-nine (34.5%) patients died in 30 days. Amikacin MIC values ranged from 0.125 to 8 μg/mL and did not influence on mortality, regardless of the prescribed dose of this antibiotic (P = 0.24). Bacterial clearance occurred in 17 (58.6%) of 29 patients who collected subsequent cultures. Two (16.6%) of the 12 persistently positive cultures changed the amikacin susceptibility profile from susceptible to intermediate. Twenty-nine (37.2%) patients developed acute kidney injury (AKI): risk 13, injury 11, and failure 5. Risk factors for AKI were higher baseline eGFR (P < 0.01) and combination therapy with colistin (P = 0.02). Comparing patients who received combination with colistin vs polymyxin B, AKI occurred in 60.0% vs 20.6%, respectively, P < 0.01. Fifteen of the 16 (16.6%) patients who developed renal injury or failure were receiving colistin. In conclusion, amikacin was an effective treatment for CRKp infections. Within susceptible range, amikacin MIC values did not influence on clinical outcomes. Combination therapy of amikacin and colistin was highly nephrotoxic and should be used with caution.
Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Treatment Outcome; Young Adult
PubMed: 34191252
DOI: 10.1007/s42770-021-00551-x -
Clinical Infectious Diseases : An... Oct 2019
Topics: Amikacin; Anti-Bacterial Agents; Child; Cystic Fibrosis; Drug Resistance, Bacterial; Humans; Mycobacterium abscessus
PubMed: 30689764
DOI: 10.1093/cid/ciz071