Clinical Pharmacokinetics of Aztreonam

Mattie, H.

doi:10.2165/00003088-199426020-00003

Cited by 18 publications

(6 citation statements)

References 36 publications

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“…Aztreonam displayed the typical ␤-lactam pharmacokinetics, with a short half-life and slow penetration into bronchial secretions, corresponding to a penetration ratio of 20% upon a single intravenous administration (172)(173)(174)(175)(176)(177). High sputum concentrations were achieved upon aerosolized administration; sputum concentrations increased dose proportionally from 383 to 879 to 985 mg/kg following aerosol delivery of 75, 150, and 225 mg.…”

Section: Serum and Sputum Pharmacokineticsmentioning

confidence: 99%

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Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

Dalhoff¹

2014

Clin Microbiol Rev

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SUMMARY Bacteria adapt to growth in lungs of patients with cystic fibrosis (CF) by selection of heterogeneously resistant variants that are not detected by conventional susceptibility testing but are selected for rapidly during antibacterial treatment. Therefore, total bacterial counts and antibiotic susceptibilities are misleading indicators of infection and are not helpful as guides for therapy decisions or efficacy endpoints. High drug concentrations delivered by aerosol may maximize efficacy, as decreased drug susceptibilities of the pathogens are compensated for by high target site concentrations. However, reductions of the bacterial load in sputum and improvements in lung function were within the same ranges following aerosolized and conventional therapies. Furthermore, the use of conventional pharmacokinetic/pharmacodynamic (PK/PD) surrogates correlating pharmacokinetics in serum with clinical cure and presumed or proven eradication of the pathogen as a basis for PK/PD investigations in CF patients is irrelevant, as minimization of systemic exposure is one of the main objectives of aerosolized therapy; in addition, bacterial pathogens cannot be eradicated, and chronic infection cannot be cured. Consequently, conventional PK/PD surrogates are not applicable to CF patients. It is nonetheless obvious that systemic exposure of patients, with all its sequelae, is minimized and that the burden of oral treatment for CF patients suffering from chronic infections is reduced.

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Section: Serum and Sputum Pharmacokineticsmentioning

confidence: 99%

“…High sputum concentrations were achieved upon aerosolized administration; sputum concentrations increased dose proportionally from 383 to 879 to 985 mg/kg following aerosol delivery of 75, 150, and 225 mg. Systemic exposure was low but occurred rapidly (Table 2) (171)(172)(173)(174)(175)(176)(177).…”

Section: Serum and Sputum Pharmacokineticsmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

Dalhoff¹

2014

Clin Microbiol Rev

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“…In these patients, either ceftolozane/tazobactam had failed or colistin had caused acute kidney injury [42]. Aztreonam penetrates the CSF more readily in patients with inflamed meninges than in the absence of meningeal inflammation [32,46]. With uninflamed meninges, 4.7 h after an i.v.…”

Section: β-Lactam Antibiotic/β-lactamase Inhibitor Combinationsmentioning

confidence: 99%

New Antibiotics for the Treatment of Nosocomial Central Nervous System Infections

Nau,

Seele,

Eiffert

2024

Antibiotics

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Nosocomial central nervous system (CNS) infections with carbapenem- and colistin-resistant Gram-negative and vancomycin-resistant Gram-positive bacteria are an increasing therapeutic challenge. Here, we review pharmacokinetic and pharmacodynamic data and clinical experiences with new antibiotics administered intravenously for the treatment of CNS infections by multi-resistant bacteria. Cefiderocol, a new siderophore extended-spectrum cephalosporin, pharmacokinetically behaves similar to established cephalosporins and at high doses will probably be a valuable addition in our therapeutic armamentarium for CNS infections. The new glycopeptides dalbavancin, telavancin, and oritavancin are highly bound to plasma proteins. Although effective in animal models of meningitis, it is unlikely that they reach effective cerebrospinal fluid (CSF) concentrations after intravenous administration alone. The β-lactam/β-lactamase inhibitor combinations have the principal problem that both compounds must achieve adequate CSF concentrations. In the commercially available combinations, the dose of the β-lactamase inhibitor tends to be too low to achieve adequate CSF concentrations. The oxazolidinone tedizolid has a broader spectrum but a less suitable pharmacokinetic profile than linezolid. The halogenated tetracycline eravacycline does not reach CSF concentrations sufficient to treat colistin-resistant Gram-negative bacteria with usual intravenous dosing. Generally, treatment of CNS infections should be intravenous, whenever possible, to avoid adverse effects of intraventricular therapy (IVT). An additional IVT can overcome the limited penetration of many new antibiotics into CSF. It should be considered for patients in which the CNS infection responds poorly to systemic antimicrobial therapy alone.

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“…Two patients with CNS infections by XDR P. aeruginosa were successfully treated with aztreonam, avibactam plus ceftazidime [78]. Aztreonam penetrates into the CSF more readily in patients with than without inflamed meninges [81,82].…”

Section: New Antibiotics Potentially Suitable For the Treatment Of Cn...mentioning

confidence: 99%

Central nervous system infections and antimicrobial resistance: an evolving challenge

Nau

Sörgel

Eiffert

2021

Current Opinion in Neurology

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Purpose of review Antimicrobial resistance is an increasing threat to patients also in nosocomial central nervous system (CNS) infections. The present review focusses on optimizing intravenous treatment in order to achieve sufficient concentrations of antibiotics in the different compartments of the CNS when the causative pathogens have reduced sensitivity to antibiotics or/and the impairment of the blood–cerebrospinal fluid (CSF) and blood–brain barrier is mild. Recent findings Experience has been gathered with treatment protocols for several established antibiotics using increased doses or continuous instead of intermittent intravenous therapy. Continuous infusion in general does not increase the average CSF concentrations (or the area under the concentration–time curve in CSF) compared to equal daily doses administered by short-term infusion. In some cases, it is postulated that it can reduce toxicity caused by high peak plasma concentrations. In case reports, new β-lactam/β-lactamase inhibitor combinations were shown to be effective treatments of CNS infections. Summary Several antibiotics with a low to moderate toxicity (in particular, β-lactam antibiotics, fosfomycin, trimethoprim-sulfamethoxazole, rifampicin, vancomycin) can be administered at increased doses compared to traditional dosing with low or tolerable adverse effects. Intrathecal administration of antibiotics is only indicated, when multiresistant pathogens cannot be eliminated by systemic therapy. Intravenous should always accompany intrathecal treatment.

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Clinical Pharmacokinetics of Aztreonam

Cited by 18 publications

References 36 publications

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

New Antibiotics for the Treatment of Nosocomial Central Nervous System Infections

Central nervous system infections and antimicrobial resistance: an evolving challenge

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