Optimization of anti‐pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: II. Cephalosporins and penicillins latest update

Abstract

To the Editor, We are writing this letter to provide an update of published information on ceftolozane-tazobactam, and ceftazidime-avibactam in cystic fibrosis (CF) to the State of the Art article "Optimization of Anti-pseudomonal Antibiotics for CF Pulmonary Exacerbations: II. Cephalosporins and Penicillins" by Zobell and colleagues. 1 This published information on ceftolozane-tazobactam and ceftazidime-avibactam were not available when the original State of the Art article was published. We would like to update the article with this information. Cephalosporins have a wide range of antimicrobial activity. However, only four of them have activity against Pseudomonas aeruginosa. 1,2 These are ceftolozane, ceftazidime, cefepime, and cefiderocol. 1-3 No information exists for cefiderocol in CF, and no new information exists for cefepime in CF so refer to the previous published article by Zobell and collegues. 1 Ceftolozane is available in combination with the beta-lactamase inhibitor, tazobactam. 2 Ceftazidime is available in combination with the beta-lactamase inhibitor, avibactam. 4 Both antibiotics share pharmacodynamic properties and side-effect profiles similar to other cephalosporins as mentioned in the previous article by Zobell et al. 1,2,4 2 | PHARMACOKINETICS/ PHARMACODYNAMICS 2.1 | Ceftolozane-tazobactam Stokem et al. 5 described the pharmacokinetic-pharmacodynamic (PK/PD) of ceftolozane-tazobactam 3 g given intravenously (IV) every 12 h (2 g ceftolozane/1 g tazobactam) in a 35-year-old female CF patient with renal insufficiency and multidrug-resistant pseudomonas. PK/PD parameters are listed in Table 1. 5 Davis et al. 6 obtained serum concentrations in a 30-year-old female CF patient with an estimated glomerular filtration of 215 ml/min at the time of serum sampling. The patient received a ceftolozane-tazobactam 3 g (2 g ceftolozane/1 g tazobactam) loading dose followed by 6 g (4 g ceftolozane/2 g tazobactam) continuous infusion over 24 h. Serum concentrations and PK/PD parameters are listed in Table 1. 6Romano et al. 7 described how patient-specific PK were used in a 63-year-old female CF patient with stage III chronic kidney disease.Ceftolozane-tazobactam 3 g was given IV every 8 h over 60 min

The indispensable role of pharmacy services and medication therapy management in cystic fibrosis

“…Ciprofloxacin 40 mg/kg/day div every 12 h 77,78 1000 mg every 12 h 77,78 2.0 g/day 77,78 Levofloxacin Insufficient evidence for recommendations 77,78 Insufficient evidence for recommendations 77,78 Insufficient evidence for recommendations 77,78 Methicillin-sensitive Staphylococcus aureus (MSSA) Cephalexin 50-100 mg/kg/day div every 6 h 67 500 mg every 6 h 67 2.0 g/day 67 Amoxicillin Ceftazidime-avibactam N/A 2.5 g every 8 h (2 g ceftazidime; 0.5 g avibactam) 85,86 7.5 g/day (6 g ceftazidime -1.5 g avibactam) 85,86 Cefepime 150-200 mg/kg/day div every 6-8 h 84 2 g every 6-8 h 84 6-8 g/day 84 Ceftolozane-tazobactam <12 years of age: 120 mg/kg/day div every 8 h 85 ≥12 years of age: 3 g every 8 h (2 g of ceftolozane; 1 g of tazobactam) 85 3 g every 8 h (2 g ceftolozane; 1 g tazobactam) 85,87 9 g/day (6 g ceftolozane; 3 g tazobactam) 85,87 Doripenem 90 mg/kg/day div every 8 h, infused over 4 h 83 2 g every 8 h, infused over 4 h 83 6 g/day 83 Imipenem-cilastatin 100 mg/kg/day div every 6 h (imipenem component) 83 1 g every 6 h (imipenem component) 83 4 g/day (imipenem component) 83 Meropenem 120 mg/kg/day div every 8 h 83 2 g every 8 h 83 6 g/day 83 Piperacillin-tazobactam 350-600 mg/kg/day (piperacillin component) div every 4 h 84 3-4 g every 4 h (piperacillin component) 84 18-24 g/day (piperacillin component) 84 Amikacin 30-35 mg/kg/day every 24 h 88 30-35 mg/kg/day every 24 h 88 Peak range: 80-120 mg/L Trough: <1 mg/L 88 Gentamicin Not recommended for routine use 88 Not recommended for routine use 88 Not rec...…”

“…The antibiotic classes most commonly utilized for APE are antipseudomonal beta‐lactams (98%) and aminoglycosides (61%–94.3%), with the combination of beta‐lactam and aminoglycoside being the most common (95.5%) (Table 3). 78,83–85,87,88,95–99 The other antipseudomonal antibiotic classes are fluoroquinolones and colistimethate sodium (Table 3). 77,78,89 …”