Beta-lactam dosing in critically ill patients with septic shock and continuous renal replacement therapy

Ulldemolins, Marta; Vaquer, Sergi; Llauradó-Serra, Mireia; Pontes, Caridad; Calvo, Gonzalo; Soy, Dolors; Martín-Loeches, Ignacio

doi:10.1186/cc13938

Critical Care

Table 1 Available data on meropenem pharmacokinetics in continuous renal replacement therapy

From: Beta-lactam dosing in critically ill patients with septic shock and continuous renal replacement therapy

Study	n	Population and score^a	Site of infection	Pathogen (MIC)	Antibiotic	Type of filter	Type of CRRT	RRT dose^a
Spanish product information	N/R	Healthy volunteers	N/A	N/A	Meropenem 2 g	N/A	N/A	N/A
Ververs and colleagues [16]	5	Critically ill patients with septic shock and AKI. No severity score reported	Several	Target: 100 % T_>MIC90 of sensitive trains (Serratia sp. 0.06 mg/l and Pseudomonas aeruginosa 2 mg/l)	Meropenem 500 mg every 12 hours	PAN 06 polyacrylonitrile fiber membrane	CVVHF	Q_R: 1.60 l/hour
Bilgrami and colleagues [15]	10	Critically ill patients with septic shock and AKI. APACHE II score 25 (22 to 28)	Several	Target: 100 % T_>MIC90 of Burkholderia pseudomallei (MIC 4 mg/l)	Meropenem 1 g every 8 hours	AN 69 HF, 2.15 m² polyacrylonitrile fiber membrane	CVVHF	Q_R: 4.40 l/hour
Krueger and colleagues [24]	8	Critically ill patients with sepsis and MODS or cardiogenic shock and AKI. APACHE II score 29.90 ± 6.64	Several	Target: 40 % T_>MIC of susceptibility and intermediate-susceptibility breakpoint (4 and 8 mg/l, NCCLS)	Meropenem 500 mg every 12 hours	AN 69 HF, 0.9 m² polyacrylonitrile fiber membrane	CVVHF	Q_R: 1.60 l/hour
Thalhammer and colleagues [18]	9	Critically ill patients with sepsis and AKI. No severity score reported	Several	Target: 40 to 50 % T_>MIC90 of P. aeruginosa susceptibility and intermediate-susceptibility breakpoint (4 and 8 mg/l, NCCLS)	Meropenem 1 g single dose	0.43 m² polysulphone fiber membrane	CVVHF	Q_R: 2.75 l/hour
Tegeder and colleagues [19]	9	Critically ill patients with septic shock and AKI. No severity score reported	Several (66.6 % abdominal)	Target: 100 % T_>MIC90 of P. aeruginosa intermediate-susceptibility breakpoint (8 mg/l)	Meropenem 500 mg every 8 to 12 hours	AN 69 HF type of membrane N/R	CVVHF	Q_R: 1 l/hour
Valtonen and colleagues [49]	6	Infected patients with AKI. No severity score reported	N/R	Target: 100 % T_>MIC90 of P. aeruginosa and Enterococcus faecalis susceptibility breakpoint (4 and 8 mg/l, BSAC)	Meropenem 1 g single dose	AV 400S, 0.7 m² polysulphone fiber membrane	CVVHDF	Q_D: 1 l/hour, Q_R: N/R
							CVVHDF	Q_D: 2 l/hour, Q_R: N/R
							CVVHF	Q_R: N/R
Robatel and colleagues [20]	13	Critically ill patients with septic shock and AKI. No severity score reported	Several	Target: ≥75 % T_>MIC90 of susceptibility breakpoint (4 mg/l)	Meropenem 0.5 to 1 g every 8 to 12 hours	AN 69 HF, 0.9 m² polyacrylonitrile fiber membrane	CVVHDF	Q_D: 0.60 to 1.50 l/hour, Q_R: 0 to 1 l/hour
Langgartner and colleagues [21]	6	Critically ill patients with sepsis and AKI. No severity score reported	Several (50 % pneumonia)	Target: 100 % T_>MICP. aeruginosa intermediate-susceptibility breakpoint (MIC 8 mg/l)	Meropenem 1 g every 12 hours (bolus or CI)	AV 600S, 1.4 m² polysulphone fiber membrane	CVVHDF	Total flow rate (Q_D + Q_R): 2 l/hour
Seyler and colleagues [22]	17	Critically ill patients with severe sepsis/septic shock and AKI. No severity score reported	N/R	Target: 40 % T_>4xMIC of P. aeruginosa susceptibility breakpoint (≤2 mg/l, EUCAST) (8 mg/l)	Meropenem 1 g every 12 hours	AN 69 HF type of membrane N/R	CVVHDF / CVVHF	Q_D: 1.61 ± 0.63, Q_R: 1.54 ± 0.84 (for a 70 kg adult, weight not reported)
Giles and colleagues [23]	5	Critically ill patients with septic shock and AKI	N/R	Target: 100 % T_>MIC90 of P. aeruginosa susceptibility breakpoint (4 mg/l)	Meropenem 1 g every 12 hours	AN 69 HF, 0.9 m² polyacrylonitrile fiber membrane	CVVHF	Q_D: 1.20 l/hour, Q_R: 1.45 l/hour
	5	Critically ill patients with septic shock and AKI	N/R	Target: 100 % T_>MIC90 of P. aeruginosa susceptibility breakpoint (4 mg/l)	Meropenem 1 g every 12 hours	AN 69 HF, 0.9 m² polyacrylonitrile fiber membrane	CVVHDF
Krueger and colleagues [17]	9	Critically ill patients with septic shock/cardiogenic shock and AKI. APACHE II 28.6 ± 9.1	Several (66.7 % pneumonia)	Target: 100 % T_>MIC of susceptibility and intermediate-susceptibility breakpoint (4 and 8 mg/l)	Meropenem 1 g every 12 hours	AN 69 HF, 0.9 m² polyacrylonitrile fiber membrane	CVVHDF	Q_D: 1.60 l/hour, Q_R: variable
Isla and colleagues [26]	7	Critically ill patients with sepsis and CrCL <10 ml/minute. SOFA 13 ± 4.12	N/R	Target: 100 % T_>MIC90 of P. aeruginosa and Enterobacteriaceae spp. susceptibility breakpoint (4 mg/l, NCCLS)	Meropenem 500 mg every 6 hours (5 cases), 500 mg every 8 hours (1 case), 1 g every 8 hours (1 case)	AN 69 HF 0.9 m² polyacrylonitrile fiber/AV600S 1.4 m² polysulphone fiber membrane	CVVHDF	Q_D: 0.93 l/hour, Q_R: 1.20 l/hour
	7	Critically ill patients with sepsis and CrCL 10 to 50 ml/minute. SOFA 12.3 ± 3.2	N/R	Target: 100 % T_>MIC90 of P. aeruginosa and Enterobacteriaceae spp. susceptibility breakpoint (4 mg/l, NCCLS)	Meropenem 500 mg every 6 hours (6 cases), 1 g every 8 hours (1 case)	AN 69 HF 0.9 m² polyacrylonitrile fiber/AV600S 1.4 m² polysulphone fiber membrane	CVVHF (4 cases) / CVVHDF (3 cases)	Q_D: 0.43 l/hour, Q_R: 1.84 l/hour
	6	Critically ill patients (mostly trauma patients) with sepsis and CrCL >50 ml/minute. SOFA 14.0 ± 5.2	N/R	Target: 100 % T_>MIC90 of P. aeruginosa and Enterobacteriaceae spp. susceptibility breakpoint (4 mg/l, NCCLS)	Meropenem 2 g every 8 hours (5 cases), 1 g every 6 hours (1 case)	AN 69 HF, 0.9 m² polyacrylonitrile fiber membrane	CVVHF	Q_R: 1.25 l/hour
Isla and colleagues [25]	13	Critically ill patients with sepsis and AKI. SOFA 11.9 ± 2.8	N/R	Target: 100 % T_>MIC90 of Enterobacteriaceae spp., P. aeruginosa and Staphylococcus aureus susceptibility and intermediate-susceptibility breakpoints (4 and 8 mg/l respectively, NCCLS)	Meropenem 500 mg, 1 to 2 g every 6 to 8 hours	AN 69 HF, 0.9 m² polyacrylonitrile fiber membrane or AV 600S, 1.4 m² polysulphone fiber membrane	CVVHF / CVVHDF	Total flow rate (Q_D + Q_R): 2.28 l/hour
Meyer and colleagues [27]	1	Critically ill patient with septic shock and AKI	Meningitis	Target: 100 % T_>MIC90 of Neisseria meningitidis susceptibility breakpoint (0.016 mg/l)	Meropenem 1 g every 12 hours for three doses then 1 g every 8 hours	AN 69 HF, type of membrane N/R	CVVHDF	Q_D: 0.75 l/hour, Q_R: 1.25 l/hour

The table includes healthy volunteers’ data with comparative purpose. AKI, acute kidney injury; APACHE, Acute Physiology and Chronic Health Evaluation; BSAC, British Society for Antimicrobial Chemotherapy; CI, continuous infusion; CrCL, creatinine clearance; CRRT, continuous renal replacement therapy; CVVHDF, continuous venovenous hemodiafiltration; CVVHF, continuous venovenous hemofiltration; EUCAST, European Committee on Antimicrobial Susceptibility Testing; MIC, minimum inhibitory concentration; MODS, multiple organ dysfunction syndrome; N/A, not applicable; NCCLS, National Committee of Clinical Laboratory Standards; N/R, not reported; Q_D, dialysis fluid flow rate; Q_R, replacement fluid flow rate; RRT, renal replacement therapy; SOFA, Sequential Organ Failure Assessment; %T_>MIC, percentage of dosing interval while concentration of the antibiotic is above the minimum inhibitory concentration of the pathogen. ^aData presented as mean ± standard deviation or median (interquartile range).

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