The pharmacokinetics of aztreonam and penetration into the bronchial secretions of critically ill patients

Boccazzi, A; Langer, Michael; Mandelli, M.; Ranzi, A. M.; Urso, R.

doi:10.1093/jac/23.3.401

Cited by 15 publications

(10 citation statements)

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“…In one study, in 10 patients the mean aztreonam concentration in bronchial secretions 0 to 2 hour after intravenous administration of aztreonam 2g was 7.5 mg/L, but this was not related to the mean plasma aztreonam concentration (Mandelli et al 1987). Similar results were reported in another study (Boccazzi et al 1989).…”

Section: Excreted Fluidssupporting

confidence: 92%

“…In 10 critically ill intubated patients with respiratory tract infections, the median V d of aztreonam was 22.5L (range 10 to 34L, with an outlier of 82L in a very obese patient) [Boccazzi et al 1989]. The CLp in these patients (median 8.7 Lib) and the CLR (median 6.7 Lib) were higher than those determined in healthy volunteers, suggesting that decreased plasma protein binding was the cause of this difference.…”

Section: Patients With Infectionsmentioning

confidence: 99%

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Clinical Pharmacokinetics of Aztreonam

Mattie

1994

Clinical Pharmacokinetics

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Plasma concentrations of aztreonam follow a 2-compartment open model with a distribution half-life of 0.20 hours after intravenous injection. The volume of distribution at steady-state (Vss) after intravenous and intramuscular injection is about 0.16 L/kg (0.42 L/kg for free drug). After intramuscular injection, absorption is almost complete. Absorption after intraperitoneal administration in patients with peritonitis is 92%. Over a large dosage range, plasma concentrations increase dose proportionally. In healthy individuals, about 56% of the drug is plasma protein bound. Diffusion into tissues is generally slow, and the ratio between mean tissue and plasma aztreonam concentration seems to depend mainly on tissue composition. Aztreonam penetrates into cerebrospinal fluid (CSF) more rapidly in patients with inflamed meninges than in those with noninflamed meninges. Diffusion through the placenta is poor, as is diffusion into breastmilk. Aztreonam is predominantly eliminated by the kidney, partly by active tubular excretion. Extrarenal clearance appears to be through hepatic excretion. Metabolism occurs to a very limited extent. Total plasma clearance (CLp) in healthy adults is about 5.6 L/h and the terminal elimination half-life is 1.7 to 2.0 hours. CLp is similar in both children and adults when expressed as a function of bodyweight. However, in neonates, especially in low birthweight infants, CLp is lower. In various disease states, the Vss of aztreonam is not appreciably different from that found in healthy individuals. However, patients with low serum albumin levels (e.g. burn patients, critically ill patients and those with cirrhosis of the liver) generally have an increased volume of distribution. The elimination half-life of the drug is dependent on renal function.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Excreted Fluidssupporting

confidence: 92%

Section: Patients With Infectionsmentioning

confidence: 99%

Clinical Pharmacokinetics of Aztreonam

Mattie

1994

Clinical Pharmacokinetics

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“…These changes were attributed to lower protein binding secondary to low serum albumin concentrations (2,15,18). Burn injury is well known to result in decreased serum albumin concentrations.…”

Section: Discussionmentioning

confidence: 99%

Aztreonam pharmacokinetics in burn patients

Friedrich

White

Kays

et al. 1991

Antimicrob Agents Chemother

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The pharmacokinetics of aztreonam in eight adult patients with severe burn injuries (total body surface area burn, 49% + 21% [mean + standard deviation]) were studied. The time of initiation of study following burn injury was 7.0 ± 1.4 days. Four patients at first dose and at steady state were studied. Aztreonam concentrations were measured by high-performance liquid chromatography, and a two-compartment model was used to fit the data. No significant differences in any pharmacokinetic parameters between first dose and steady state were observed. Volume of distribution of the central compartment after first dose (0.14 liters/kg) and volume of distribution at steady state (0.31 liters/kg) were approximately 30% higher than those reported for other patient populations. Total drug clearance and renal drug clearance when normalized to creatinine clearance (CLCR) were similar to those previously reported for other critically ill patients. CLCR was strongly correlated with renal drug clearance (r = 0.94) and total drug clearance (r = 0.95). The extent and degree of burn (percent second or third degree burn) were poorly correlated with all pharmacokinetic parameters with the exception of the volume of distribution at steady state, which was correlated with both total body surface area burn (r = 0.95) and percent second degree burn (r = 0.83). Aztreonam pharmacokinetics are altered as a result of thermal injury; however, CLCR can be used to assess the clearance of aztreonam in burn patients.

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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%

“…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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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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The pharmacokinetics of aztreonam and penetration into the bronchial secretions of critically ill patients

Cited by 15 publications

References 0 publications

Clinical Pharmacokinetics of Aztreonam

Clinical Pharmacokinetics of Aztreonam

Aztreonam pharmacokinetics in burn patients

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

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