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The Medical Clinics of North America Jul 1995Aztreonam is a monocyclic beta-lactam antibiotic that is active exclusively against the aerobic gram-negative bacilli. It is not ototoxic or nephrotoxic and so is used... (Review)
Review
Aztreonam is a monocyclic beta-lactam antibiotic that is active exclusively against the aerobic gram-negative bacilli. It is not ototoxic or nephrotoxic and so is used as an alternative to aminoglycosides in a variety of clinical situations. In polymicrobial infections or when used for empiric therapy, aztreonam must be combined with other antimicrobial agents active against gram-positive and anaerobic species. Aztreonam is often effective against resistant strains of gram-negative organisms, which are often involved in nosocomial infections. Overuse of aztreonam should be avoided to prevent the emergence of resistant P. aeruginosa strains. Except in the treatment of P. aeruginosa infections, aztreonam should not be added to beta-lactam regimens for additional gram-negative coverage.
Topics: Aztreonam; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests
PubMed: 7791420
DOI: 10.1016/s0025-7125(16)30036-0 -
The Journal of Antimicrobial... Oct 2023Critically ill patients have increased variability in beta-lactam antibiotic (beta-lactam) exposure due to alterations in their volume of distribution and elimination.... (Review)
Review
Critically ill patients have increased variability in beta-lactam antibiotic (beta-lactam) exposure due to alterations in their volume of distribution and elimination. Therapeutic drug monitoring (TDM) of beta-lactams, as a dose optimization and individualization tool, has been recommended to overcome this variability in exposure. Despite its potential benefit, only a few centres worldwide perform beta-lactam TDM. An important reason for the low uptake is that the evidence for clinical benefits of beta-lactam TDM is not well established. TDM also requires the availability of specific infrastructure, knowledge and expertise. Observational studies and systematic reviews have demonstrated that TDM leads to an improvement in achieving target concentrations, a reduction in potentially toxic concentrations and improvement of clinical and microbiological outcomes. However, a small number of randomized controlled trials have not shown a mortality benefit. Opportunities for improved study design are apparent, as existing studies are limited by their inclusion of heterogeneous patient populations, including patients that may not even have infection, small sample size, variability in the types of beta-lactams included, infections caused by highly susceptible bacteria, and varied sampling, analytical and dosing algorithm methods. Here we review the fundamentals of beta-lactam TDM in critically ill patients, the existing clinical evidence and the practical aspects involved in beta-lactam TDM implementation.
Topics: Humans; Anti-Bacterial Agents; Drug Monitoring; Critical Illness; beta-Lactams; Critical Care; Monobactams
PubMed: 37466209
DOI: 10.1093/jac/dkad223 -
Antimicrobial Agents and Chemotherapy Jul 2023The impact of broad-spectrum β-lactamases on the susceptibility to novel β-lactamase/β-lactamase inhibitor combinations was evaluated both in Pseudomonas aeruginosa...
Impact of Acquired Broad Spectrum β-Lactamases on Susceptibility to Novel Combinations Made of β-Lactams (Aztreonam, Cefepime, Meropenem, and Imipenem) and Novel β-Lactamase Inhibitors in Escherichia coli and Pseudomonas aeruginosa.
The impact of broad-spectrum β-lactamases on the susceptibility to novel β-lactamase/β-lactamase inhibitor combinations was evaluated both in Pseudomonas aeruginosa and Escherichia coli using isogenic backgrounds. Cefepime-zidebactam displayed low MICs, mainly due to the significant intrinsic antibacterial activity of zidebactam. Cefepime-taniborbactam showed excellent activity against recombinant E. coli strains, including metallo-β-lactamase producers, whereas aztreonam-avibactam remained the best therapeutic option against class B β-lactamase-producing P. aeruginosa.
Topics: Cefepime; beta-Lactamase Inhibitors; Meropenem; beta-Lactams; Aztreonam; Imipenem; Pseudomonas aeruginosa; Escherichia coli; beta-Lactamases; Anti-Bacterial Agents; Azabicyclo Compounds; Microbial Sensitivity Tests
PubMed: 37255469
DOI: 10.1128/aac.00339-23 -
Therapeutic Drug Monitoring Oct 2023Recently, several studies have assessed the effects of therapeutic drug monitoring of frequently prescribed beta-lactam antibiotics, for which they were quantified in...
BACKGROUND
Recently, several studies have assessed the effects of therapeutic drug monitoring of frequently prescribed beta-lactam antibiotics, for which they were quantified in human plasma samples. Beta-lactams are considered unstable, leading to extra challenges in quantification. Therefore, to ensure sample stability and minimize sample degradation before analysis, stability studies are crucial. This study investigated the stability of 10 frequently used beta-lactam antibiotics in human plasma at relevant storage conditions for clinical use.
METHODS
Amoxicillin, benzylpenicillin, cefotaxime, ceftazidime, ceftriaxone, cefuroxime, flucloxacillin, imipenem, meropenem, and piperacillin were analyzed using ultraperformance convergence chromatography tandem mass spectrometry and liquid chromatography tandem mass spectrometry. Their short-term and long-term stabilities were investigated by measuring quality control samples at low and high concentrations against freshly prepared calibration standards. Measured concentrations at each time point were compared with the concentrations at T = 0. Antibiotics were considered stable if recovery results were between 85% and 115%.
RESULTS
Short-term stability results indicated ceftriaxone, cefuroxime, and meropenem to be stable up to 24 hours at room temperature. All evaluated antibiotics, except imipenem, were stable on ice in a cool box for 24 hours. Amoxicillin, benzylpenicillin, and piperacillin were stable for 24 hours at 4-6°C. Cefotaxime, ceftazidime, cefuroxime, and meropenem were stable at 4-6°C up to 72 hours. Ceftriaxone and flucloxacillin were stable for 1 week at 4-6°C. Long-term stability results showed that all antibiotics were stable up to 1 year at -80°C, except imipenem and piperacillin, which were stable for 6 months at -80°C.
CONCLUSIONS
Plasma samples for amoxicillin, benzylpenicillin, cefotaxime, ceftazidime, flucloxacillin, and piperacillin may be stored for a maximum of 24 hours in a cool box. Refrigeration is suitable for plasma samples of amoxicillin, benzylpenicillin, meropenem, and piperacillin for up to 24 hours and cefotaxime, ceftriaxone, ceftazidime and cefuroxime for 72 hours. Plasma samples for imipenem should be frozen directly at -80°C. For long-term storage, plasma samples can be stored at -80°C for a maximum of 6 months for imipenem and piperacillin and 12 months for all other evaluated antibiotics.
Topics: Humans; Meropenem; Ceftazidime; Floxacillin; Cefuroxime; Ceftriaxone; Anti-Bacterial Agents; Piperacillin; Monobactams; Tandem Mass Spectrometry; Imipenem; Cefotaxime; Amoxicillin
PubMed: 37199408
DOI: 10.1097/FTD.0000000000001100 -
Current Opinion in Microbiology Oct 2010In the 80 years since their discovery the β-lactam antibiotics have progressed through structural generations, each in response to the progressive evolution of... (Review)
Review
In the 80 years since their discovery the β-lactam antibiotics have progressed through structural generations, each in response to the progressive evolution of bacterial resistance mechanisms. The generational progression was driven by the ingenious, but largely empirical, manipulation of structure by medicinal chemists. Nonetheless, the true creative force in these efforts was Nature, and as the discovery of new β-lactams from Nature has atrophied while at the same time multi-resistant and opportunistic bacterial pathogens have burgeoned, the time for empirical drug discovery has passed. We concisely summarize recent developments with respect to bacterial resistance, the identity of the new β-lactams, and the emerging non-empirical strategies that will ensure that this incredible class of antibiotics has a future.
Topics: Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Cephalosporins; Monobactams; beta-Lactam Resistance; beta-Lactamases; beta-Lactams
PubMed: 20888287
DOI: 10.1016/j.mib.2010.09.008 -
Frontiers in Cellular and Infection... 2023β-lactam antibiotics are the most frequently used drugs and the most common drugs that cause allergic reactions in pediatrics. The occurrence of some allergic reactions... (Review)
Review
β-lactam antibiotics are the most frequently used drugs and the most common drugs that cause allergic reactions in pediatrics. The occurrence of some allergic reactions can be predicted by skin testing, especially severe adverse reactions such as anaphylactic shock. Thus, penicillin and cephalosporin skin tests are widely used to predict allergic reactions before medication in pediatrics. However, false-positive results from skin tests were more often encountered in pediatrics than in adults. In fact, many children labeled as allergic to β-lactam are not allergic to the antibiotic, leading to the use of alternative antibiotics, which are less effective and more toxic, and the increase of antibiotic resistance. There has been controversy over whether β-lactam antibiotics should be tested for skin allergies before application in children. Based on the great controversy in the implementation of β-lactam antibiotic skin tests, especially the controversial cephalosporin skin tests in pediatrics, the mechanism and reasons of anaphylaxis to β-lactam antibiotics, the significance of β-lactam antibiotic skin tests, the current state of β-lactam antibiotic skin tests at home and abroad, and the problems of domestic and international skin tests were analyzed to determine a unified standard of β-lactam antibiotic skin tests in pediatrics to prevent and decrease adverse drug reactions, avoid waste of drugs, and a large amount of manpower and material resource consumption.
Topics: Adult; Child; Humans; Drug Hypersensitivity; Skin Tests; Anti-Bacterial Agents; beta-Lactams; Penicillins; Monobactams; Cephalosporins; Anaphylaxis; Pediatrics
PubMed: 37396306
DOI: 10.3389/fcimb.2023.1147976 -
Journal of Clinical Microbiology Oct 2023Aztreonam-avibactam (AZA), a newly developed β-lactam/β-lactamase inhibitor combination is a treatment option for infections due to carbapenem-resistant...
Aztreonam-avibactam (AZA), a newly developed β-lactam/β-lactamase inhibitor combination is a treatment option for infections due to carbapenem-resistant Enterobacterales (CRE), including metallo-ß-lactamase producers, regardless of additional production of broad-spectrum serine-ß-lactamases. However, AZA-resistance has already been reported in Enterobacterales and its early detection could be a valuable tool for faster and more accurate clinical decision-making. We therefore developed a rapid culture-based test for the identification of AZA resistance among multidrug-resistant Enterobacterales. The Rapid Aztreonam/Avibactam NP test is based on resazurin reduction when bacterial growth occurs in the presence of AZA at 8/4 µg/mL (protocol 1) or 12/4 µg/mL (protocol 2). Given the absence of guidelines on AZA susceptibility testing, two tentative breakpoints were indeed used to categorize AZA-susceptible isolates: ≤4 µg/mL in protocol 1 and ≤ 8 µg/mL in protocol 2. Bacterial growth was visually detectable by a blue-to-purple or blue-to-pink color change of the medium. A total of 78 enterobacterial isolates (among which 34 AZA-resistant and 13 AZA-resistant according to protocols 1 and 2, respectively) were used to evaluate the test performance using protocol 1 or protocol 2. The sensitivity and specificity of the test were found to be 100% and 97.7%, respectively, following protocol 1 and 100% and 100%, respectively, following protocol 2, in comparison with broth microdilution. All results were obtained within 4.5 hours corresponding to a time saving of ca. 14 hours compared with currently available methods for AZA susceptibility testing. The Rapid Aztreonam/Avibactam NP test is rapid, highly sensitive, specific, easily interpretable, and easy to implement in routine.
Topics: Humans; Aztreonam; Anti-Bacterial Agents; beta-Lactamases; Azabicyclo Compounds; beta-Lactamase Inhibitors; Microbial Sensitivity Tests; Drug Combinations; Ceftazidime
PubMed: 37791761
DOI: 10.1128/jcm.00588-23 -
Antimicrobial Agents and Chemotherapy Dec 2023Cefiderocol is a siderophore cephalosporin that binds ferric iron and utilizes iron transporters to cross the cell membrane. Hypervirulent (hvKp) is known to produce...
Cefiderocol is a siderophore cephalosporin that binds ferric iron and utilizes iron transporters to cross the cell membrane. Hypervirulent (hvKp) is known to produce more siderophores; in this case, the uptake of cefiderocol may be decreased. Therefore, the objective of this study was to evaluate the activity of cefiderocol against hvKp isolates. A total of 320 carbapenem-resistant (CRKp) isolates were collected in China between 2014 and 2022, including 171 carbapenem-resistant hvKp (CR-hvKp) and 149 carbapenem-resistant classical (CR-cKp). Quantitative detection of siderophores showed that the average siderophore production of CR-hvKp (234.6 mg/L) was significantly higher than that of CR-cKp (68.9 mg/L, < 0.001). The overall cefiderocol resistance rate of CR-hvKp and CR-cKp was 5.8% (10/171) and 2.7% (4/149), respectively. The non-susceptible rates of both cefiderocol and siderophore production of CR-hvKp isolates were higher than those of CR-cKp in either NDM-1- or KPC-2-producing groups. The MIC90 and MIC50 for CR-hvKp and CR-cKp were 8 mg/L and 2 mg/L and 4 mg/L and 1 mg/L, respectively. The cumulative cefiderocol MIC distribution for CR-hvKp was significantly lower than that of CR-cKp isolates ( = 0.003). KL64 and KL47 consisted of 53.9% (83/154) and 75.7% (53/70) of the ST11 CR-hvKp and CR-cKp, respectively, and the former had significantly higher siderophore production. In summary, cefiderocol might be less effective against CR-hvKp compared with CR-cKp isolates, highlighting the need for caution regarding the prevalence of cefiderocol-resistant strains, particularly in CR-hvKp isolates.
Topics: Humans; Cephalosporins; Cefiderocol; Siderophores; Klebsiella pneumoniae; Klebsiella Infections; Carbapenems; Monobactams; China; Iron; Carbapenem-Resistant Enterobacteriaceae; Anti-Bacterial Agents
PubMed: 38014944
DOI: 10.1128/aac.00735-23 -
Antimicrobial Agents and Chemotherapy Sep 2020This study aimed to evaluate the antimicrobial activity of the novel monosulfactam 0073 against multidrug-resistant Gram-negative bacteria and and to characterize the...
This study aimed to evaluate the antimicrobial activity of the novel monosulfactam 0073 against multidrug-resistant Gram-negative bacteria and and to characterize the mechanisms underlying 0073 activity. The activities of 0073, aztreonam, and the combination with avibactam were assessed by MIC and time-kill assays. The safety of 0073 was evaluated using 3-(4,5-dimethylthizol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and acute toxicity assays. Murine thigh infection and pneumonia models were employed to define efficacy. A penicillin-binding protein (PBP) competition assay and confocal microscopy were conducted. The inhibitory action of 0073 against β-lactamases was evaluated by the half-maximal inhibitory concentration (IC), and resistance development was evaluated via serial passage. The monosulfactam 0073 showed promising antimicrobial activity against , , and isolates producing metallo-β-lactamases (MBLs) and serine β-lactamases. In preliminary experiments, compound 0073 exhibited safety both and In the murine thigh infection model and the pneumonia models in which infection was induced by and , 0073 significantly reduced the bacterial burden. Compound 0073 targeted several PBPs and exerted inhibitory effects against some serine β-lactamases. Finally, 0073 showed a reduced propensity for resistance selection compared with that of aztreonam. The novel monosulfactam 0073 exhibited increased activity against β-lactamase-producing Gram-negative organisms compared with the activity of aztreonam and showed good safety profiles both and The underlying mechanisms may be attributed to the affinity of 0073 for several PBPs and its inhibitory activity against some serine β-lactamases. These data indicate that 0073 represents a potential treatment for infections caused by β-lactamase-producing multidrug-resistant bacteria.
Topics: Animals; Anti-Bacterial Agents; Azabicyclo Compounds; Aztreonam; Enterobacteriaceae; Mice; Microbial Sensitivity Tests; beta-Lactamase Inhibitors; beta-Lactamases
PubMed: 32718961
DOI: 10.1128/AAC.00529-20 -
Journal of Global Antimicrobial... Dec 2023This work aimed to describe the in vitro performance of the combined activity of ceftazidime-avibactam (CZA) plus aztreonam (ATM) against carbapenemase-producing...
OBJECTIVE
This work aimed to describe the in vitro performance of the combined activity of ceftazidime-avibactam (CZA) plus aztreonam (ATM) against carbapenemase-producing Enterobacterales (CPE).
METHODS
We studied 44 CPE clinical isolates: NDM-1 (31), KPC-2 (5), KPC-3 (3), VIM-2 (2), NDM-1+KPC-2 (2), and OXA-48 (1). The efficacy of CZA in combination with were determined by two methods: (i) Kirby-Bauer's double disk synergy test and; (ii) Determination of the minimum inhibitory concentration to CZA by E-test, in either Mueller-Hinton agar alone or, supplemented with ATM 4 mg/L. Additionally, the Fractional inhibitory concentration index (FICI) was determined; values of ≤ 0.5 were interpreted as synergistic, while FICI > 0.5 were considered indifferent.
RESULTS
All isolates were carbapenem-resistant, 14 were resistant to CZA and ATM, 15 were only CZA resistant, 12 were only ATM resistant, and three were susceptible to both. 34/44 isolates presented positive double disk synergy tests between CZA and ATM regardless of their susceptibility profile, the isolates with negative synergy tests were susceptible to at least one of the agents. On the other hand, the 21 isolates selected to compare the MIC to CZA alone and CZA plus 4 mg/L ATM of exhibited FICI values between 0.016 and 0.125, indicating a synergistic effect.
CONCLUSIONS
This method is available to clinical laboratories and would provide valuable information to guide the treatment of infections with CZA and ATM. In this sense, the use of CZA together with ATM is a potentially suitable combination for the treatment of carbapenemase-producing microorganisms.
Topics: Aztreonam; Anti-Bacterial Agents; Ceftazidime
PubMed: 37611893
DOI: 10.1016/j.jgar.2023.08.010