Telavancin Hospital-Acquired Pneumonia Trials: Impact of Gram-Negative Infections and Inadequate Gram-Negative Coverage on Clinical Efficacy and All-Cause Mortality

Lacy, Melinda K.; Stryjewski, Martín E.; Wang, Whedy; Hardin, Thomas C.; Nogid, Boris; Luke, David R.; Shorr, Andrew F.; Corey, G. Ralph; Barriere, Steven L.

doi:10.1093/cid/civ536

Cited by 24 publications

(18 citation statements)

References 8 publications

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“…At present, black box warnings are issued for telavancin regarding nephrotoxicity and increased mortality in patients with preexisting moderate/severe impaired kidney function (creatinine clearance ,50 ml/min) who are being treated for hospital-acquired or ventilatorassociated bacterial pneumonia (34). A post hoc analysis of the Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia (ATTAIN) trials suggests that the increased mortality in this patient population may have been related to a greater number of patients with Gramnegative organisms at baseline in the telavancin groups and by inadequate treatment of these Gram-negative organisms (36). Furthermore, in patients with severe kidney dysfunction or requiring hemodialysis, it has been demonstrated that telavancin's biologic activity against S. aureus is maintained (37).…”

Section: Lipoglycopeptidesmentioning

confidence: 99%

Clinical Pharmacology of Antibiotics

Eyler

Shvets

2019

CJASN

134

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Antimicrobial pharmacology and its effect on prescribing is quite complex. Selecting an antibiotic that will optimally treat an infection while minimizing adverse effects and the development of resistance is only the first step, as one must also consider the patient's individual pharmacokinetic alterations and the pharmacodynamic properties of the drug when prescribing it as well. Patients with CKD may have alterations in their protein binding, volumes of distribution, kidney clearance, and nonrenal clearance that necessitates antibiotic dose adjustments to prevent the development of toxicity. Knowledge of a drug's pharmacodynamics, defined as the relationship between drug exposure and antibacterial efficacy, provides some guidance regarding the optimal way to make dose adjustments. Different pharmacodynamic goals, such as maximizing the time that free (unbound) drug concentrations spend above the minimum inhibitory concentration (MIC) for time dependent drugs (e.g., b-lactams) or maximizing the free peak-to-MIC ratio for concentration-dependent antibiotics (e.g., aminoglycosides), require different adjustment strategies; for instance, decreasing the dose while maintaining normal dosing frequency or giving normal (or even larger) doses less frequently, respectively. Patients receiving hemodialysis have other important prescribing considerations as well. The nephrologist or patient may prefer to receive antibiotics that can be administered intravenously toward the end of a dialysis session. Additionally, newer dialysis technologies and filters can increase drug removal more than originally reported. This review will discuss the place in therapy, mechanism of action, pharmacokinetic, pharmacodynamic, and other pharmacologic considerations encountered when prescribing commonly used antibiotics in patients with chronic kidney disease or ESKD.

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Section: Lipoglycopeptidesmentioning

confidence: 99%

Clinical Pharmacology of Antibiotics

Eyler

Shvets

2019

CJASN

134

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“…Appropriate initial antibiotic therapy has been demonstrated as the key independent factor of treatment outcomes in patients with Gram-negative bacteremia in several previous studies [11][12][13][14].…”

Section: Introductionmentioning

confidence: 98%

Risk factors of initial inappropriate antibiotic therapy and the impacts on outcomes of neonates with gram-negative bacteremia

Chu

Hsu

Lai

et al. 2019

Preprint

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Background Timely appropriate empirical antibiotic plays an important role in critically ill patients with gram-negative bacteremia. However, the relevant data and significant impacts have not been well studied in the neonatal intensive care unit (NICU).Methods An 8-year (1 January 2007-31 December 2014) cohort study of all NICU patients with gram-negative bacteremia in a tertiary-care medical center was performed. Inadequate empirical antibiotic therapy was defined when a patient didn’t receive any antimicrobial agent to which the causative microorganisms were susceptible within 24 hour of blood culture sampling.Results Among 376 episodes of Gram-negative bacteremia, 75 (19.9%) received inadequate empirical antibiotic therapy. The cause of inadequate treatment was mostly due to the pathogen resistant to prescribed antibiotics (88.0%), and Pseudomonas aeruginosa (Odds ratio [OR]: 20.8, P < 0.001) and ESBL-producing bacteria (OR: 18.4, P < 0.001) had the highest risk. Previous exposure with 3rd generation cephalosporin was identified as the only independent risk factor (OR: 2.52, 95% CI: 1.18-5.37, P = 0.018). Empirically inadequately treated bacteremias were significantly more likely to have worse outcomes than those with adequate therapy, including more prolonged illness, higher rate of infectious complications (25.3% versus 9.3%, P < 0.001) and overall mortality (22.7% versus 11.0%, P = 0.013).Conclusions Inadequate empirical antibiotic therapy occurs in one-fifth of Gram-negative bacteremias in the NICU, and is associated with worse outcomes. Further effort to decrease emergence of antibiotic resistance and highly suspicion of infection by drug-resistant bacteria clinically is important to reduce rates of inadequacy.

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“…Appropriate initial antibiotic therapy has been demonstrated as the key independent factor of treatment outcomes in patients with Gram-negative bacteremia in previous studies from the adult ICUs or wards [11][12][13][14]. However, this issue has not been fully studied in the NICU, except for a small sample size, case-control study found in the literature [15].…”

Section: Introductionmentioning

confidence: 99%

Risk Factors of Initial Inappropriate Antibiotic Therapy and the Impacts on Outcomes of Neonates with Gram-Negative Bacteremia

et al. 2020

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Background: Timely appropriate empirical antibiotic plays an important role in critically ill patients with gram-negative bacteremia. However, the relevant data and significant impacts have not been well studied in the neonatal intensive care unit (NICU). Methods: An 8-year (1 January 2007–31 December 2014) cohort study of all NICU patients with gram-negative bacteremia (GNB) in a tertiary-care medical center was performed. Inadequate empirical antibiotic therapy was defined when a patient did not receive any antimicrobial agent to which the causative microorganisms were susceptible within 24 h of blood culture sampling. Neonates with GNB treated with inadequate antibiotics were compared with those who received initial adequate antibiotics. Results: Among 376 episodes of Gram-negative bacteremia, 75 (19.9%) received inadequate empirical antibiotic therapy. The cause of inadequate treatment was mostly due to the pathogen resistance to prescribed antibiotics (88.0%). Bacteremia caused by Pseudomonas aeruginosa (Odds ratio [OR]: 20.8, P < 0.001) and extended spectrum β-lactamase (ESBL)-producing bacteria (OR: 18.4, P < 0.001) had the highest risk of inadequate treatment. Previous exposure with third generation cephalosporin was identified as the only independent risk factor (OR: 2.52, 95% CI: 1.18–5.37, P = 0.018). Empirically inadequately treated bacteremias were significantly more likely to have worse outcomes than those with adequate therapy, including a higher risk of major organ damage (20.0% versus 6.6%, P < 0.001) and infectious complications (25.3% versus 9.3%, P < 0.001), and overall mortality (22.7% versus 11.0%, P = 0.013). Conclusions: Inadequate empirical antibiotic therapy occurs in one-fifth of Gram-negative bacteremias in the NICU, and is associated with worse outcomes. Additional prospective studies are needed to elucidate the optimal timing and aggressive antibiotic regimen for neonates who are at risk of antibiotic-resistant Gram-negative bacteremia.

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Telavancin Hospital-Acquired Pneumonia Trials: Impact of Gram-Negative Infections and Inadequate Gram-Negative Coverage on Clinical Efficacy and All-Cause Mortality

Cited by 24 publications

References 8 publications

Clinical Pharmacology of Antibiotics

Clinical Pharmacology of Antibiotics

Risk factors of initial inappropriate antibiotic therapy and the impacts on outcomes of neonates with gram-negative bacteremia

Risk Factors of Initial Inappropriate Antibiotic Therapy and the Impacts on Outcomes of Neonates with Gram-Negative Bacteremia

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