Table 1.
Extended or continuous infusion of meropenem vs intermittent administration
| Study design | Mode of administration and dosage | Pathogen and patients | Outcomes |
|---|---|---|---|
| Prospective randomized clinical trial | Prolonged infusion of meropenem over 4 h vs conventional infusion (30 min); 20 mg/kg/dose every 8 h and 40 mg/kg/dose every 8 h | Meningitis and Pseudomonas infection in neonates with Gramnegative late-onset sepsis | Higher clinical improvement (61% vs 33%, P=0.009) and microbiologic eradication at the 7th day of meropenem therapy (82% vs 56.8%, P=0.009), lower neonatal mortality (14% vs 31%, P=0.03), shorter duration of respiratory support (12.5 days vs 4 days, P=0.03), and less acute kidney injury (6% vs 23.5%, P=0.02).10 |
| Retrospective observational study | 4 h extended infusion of meropenem (1 g/8 h) vs conventional 30 min short infusion at the same dose | Adult patients with febrile neutropenia | Better clinical outcome (ie, fewer additional antibiotics during the first 5 days of treatment, a more prompt defervescence and a faster decrease in C-reactive protein level) (P<0.05) despite comparable LOS in the hospital and mortality rate between two groups.11 |
| Randomized clinical trial | Continuous group: a loading dose of 0.5 g of meropenem infused over 30 min followed by continuous infusion of 3 g/day, which was divided into six consecutive 4 h continuous infusions of meropenem 0.5 g; intermittent group: an initial dose of 1.5 g followed by 1 g infused over 30 min every 8 h. | Adult patients with severe sepsis and septic shock | Continuous infusion of meropenem provided significantly shorter treatment duration (7.6 vs 9.4 days; P=0.035) while clinical success was similar between both groups. For medium- susceptibility pathogens, concentrations above the MIC in the continuous infusion group were 100%, which was better than that in the intermittent group.12 |
| Observational study using a population PK/PD model | 3 h and 30 min infusion regimens at a dose of meropenem 1 g (twice or thrice daily) | Adult critically ill patients | The PTA, T>MIC of 100%, was higher for 3 h infusion regimen compared with 30 min infusion regimen for all ranges of creatinine clearance.13 |
| Comparative study using an in vitro PK/PD model | Short (0.5 h) and prolonged (3 h) infusion regimens of 1 g meropenem every 8 h | Different adult patient groups with CPKP isolates | ICU patients exhibited the lowest target attainment rates, whereas internal medicine patients achieved the highest target attainment rates.14 The PTA (ie, 40% T>MIC) with short infusion was higher than those with prolonged infusion for isolates with MIC 4–8 mg/L rather than MIC ≥16 mg/L or ≤2 mg/L (MIC 4 mg/L: 98%–99% vs 61%–83%; MIC 8 mg/L: 55%–79% vs 23%–33%).14 |
| Observational pharmacokinetic study using Monte Carlo simulations | Meropenem as sole agent or in combination with other antimicrobials | Acinetobacter baumannii and Pseudomonas aeruginosa infections in adult patients with septic shock | Intermittent dosing of 1 g/8 h (30 min) seemed sufficient in patients with normal renal function, whereas increasing doses (2 g/6 h for A. baumannii, 2 g/8 h or 1 g/6 h for P. aeruginosa) by intermittent (30 min) or prolonged (3 h) infusion or continuous infusion (6 g over 24 h) could increase the possibility of achieving therapeutic drug concentrations in patients with septic shock and possible augmented renal clearance.15 |
| Prospective, multicenter pharmacokinetic point-prevalence study with a post hoc analysis | Intermittent-bolus administration vs prolonged infusion | Critically ill patients | Compared with intermittent-bolus administration, prolonged infusion demonstrated significantly better 30-day survival in the subgroup of patients with respiratory infection (86.2% vs 56.7%; P=0.012), and higher clinical cure rate (73.3% vs 35.0%; P= 0.035) and survival rates (73.3% vs 25.0%; P=0.025) in patients with a SOFA score of ≥9. However, two infusion methods did not exhibit a significant difference in 30-day survival rate in patients receiving antimicrobial treatment and in the subgroup of patients with abdominal infection.16 |
| Multicenter study using population pharmacokinetics analysis | Prolonged 3 h infusion vs 30 min infusion of meropenem 40 mg/kg every 8 h | Children with cystic fibrosis | At MICs of 1, 2, and 4 mg/L, PTAs for the 0.5 h infusion were 87.6%, 70.1%, and 35.4%, respectively. Prolonged infusion increased PTAs to >99% for these MICs and achieved 82.8% at 8 mg/L, ie, 3 h infusion provided an exposure benefit against pathogens with MICs ≥1 mg/L.17 |
| Randomized controlled trial | Meropenem administered as a 1 g, 30 min infusion or as a 500 mg, 3 h infusion | Critically ill patients | Meropenem 1 g infused over 30 min could achieve a similar %T>MIC to meropenem 500 mg given over 3 h in critically ill patients. For low MICs (≤2 mg/L), both regimens attained a %T>MIC>40% in all patients. For an MIC of 4 mg/L, this target was attained in all but one patient; however, with an MIC of 8 mg/L, three patients in each group had a %T>MIC<40%. For MICs up to 8 mg/L, the two regimens exhibited no difference in target attainment.18 |
Abbreviations: CPKP, carbapenemase-producing Klebsiella pneumoniae; h, hours; ICU, intensive care unit; LOS, length of stay; MIC, minimum inhibition concentration; min, minutes; PK/PD, pharmacokinetic/pharmacodynamic; PTA, probability of target attainment; SOFA, sequential organ failure assessment; T>MIC, time for which drug concentrations exceed the MIC.