title: Non-CNS and Non-Pseudomonas Sepsis
text: |
  Non-CNS and Non-Pseudomonas Sepsis
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  bet | 350/654 | Sana | 03.01.2022 | Hajmi | 1,5 Mb. | | #14803 |
  Non-CNS and Non-Pseudomonas Sepsis
  Gestational Age at birth
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  Postnatal Age
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  Dose
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  Interval
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  < 32+0 weeks
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  0–13 days
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  20 mg/kg
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  12 hourly
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  < 32+0 weeks
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  14+ days
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  20 mg/kg
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  8 hourly
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  ≥ 32+0 weeks
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  0–13 days
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  20 mg/kg
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  8 hourly
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  ≥ 32+0 weeks
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  14+ days
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  30 mg/kg
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  8 hourly
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  Meningitis and Pseudomonas Sepsis
  Gestational Age at birth
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  Postnatal Age
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  Dose
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  Interval
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  Any
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  Any
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  40 mg/kg
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  8 hourly
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  Dose adjustment
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  Assess for renal impairment prior to using higher doses as meropenem is primarily excreted via kidneys.
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  Maximum dose
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  Total cumulative dose
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  Route
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  IV infusion.
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  Preparation
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  Infants ≤1kg
  Add 9.6 mL of water for injection to 500 mg vial to make a 50 mg/mL solution OR
  Add 19.1 mL of water for injection to 1g vial to make a 50 mg/mL solution.
  FURTHER DILUTE
  Draw up 2 mL (100 mg of meropenem) of the above solution and add 8 mL sodium chloride 0.9% to make a final volume of 10 mL with a final concentration of 10 mg/mL.
  Infants >1kg or fluid restricted.
  Add 9.6 mL of water for injection to 500 mg vial to make a 50 mg/mL solution.
  FURTHER DILUTE
  Draw up 4 mL (200 mg of meropenem) of the above solution and add 6 mL sodium chloride 0.9% to make a final volume of 10 mL with a concentration of 20 mg/mL.
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  Administration
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  IV infusion over 4 hours. (5)
  May be given over 15 to 30 minutes if longer infusion time is not feasible.
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  Monitoring
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  Renal function.
  Liver function.
  Electrolytes
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  Contraindications
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  Hypersensitivity to penicillins, cephalosporins and carbapenems.
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  Precautions
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  Colitis−due to risk of pseudomembranous colitis.
  Renal impairment.
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  Drug interactions
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  Sodium valproate− meropenem may result in clinically significant reduction in concentration of sodium valproate, which may cause seizures.
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  Adverse reactions
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  Phlebitis, diarrhoea (up to 6% in children), anaemia and eosinophilia.
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  Compatibility
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  Fluids: sodium chloride 0.9% (preferred for stability), glucose 5%, glucose 10%,
  Y-site: Amino acid solutions, anidulafungin, caspofungin, linezolid, atropine, dexamethasone sodium, gentamicin, heparin sodium, metronidazole.
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  Incompatibility
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  Fluids: Mannitol 10%
  Y-site: Dolasetron, ketamine, zidovudine.
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  Stability
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  Use immediately after preparation.
  Diluted solutions are potentially unstable, particularly glucose containing solutions and should be discarded if not used immediately.
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  Storage
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  Vial: Store at room temperature.
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  Excipients
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  Sodium carbonate
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  Meropenem 1 g vial contains 3.92 mmol of sodium.
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  Evidence
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  Efficacy:
  Carbapenems may be considered the treatment of choice for empirical treatment of patients with ESBL-producing Enterobacteriaceae bacteraemia. A systematic review of carbapenems for the treatment of patients with extended-spectrum β-lactamase (ESBL)-positive Enterobacteriaceae bacteraemia involving 1584 patients, mostly adults showed lower mortality than non-Beta-lactam/Beta-Lactam Inhibitor combination antibiotics for definitive [risk ratio (RR) 0.65, 95% CI 0.47–0.91] and empirical (RR 0.50, 95% CI 0.33–0.77) treatment. No statistically significant differences in mortality were found between carbapenems and BL/BLIs administered as definitive (RR 0.52, 95% 0.23–1.13) or empirical (RR 0.91, 95% CI 0.66–1.25) treatment (LOE 1, GOR C).2
  A retrospective case series of 100 neonates infected by extended-spectrum beta-lactamase-producing Klebsiella species showed higher mortality in those neonates not started on empirical meropenem or Piperacillin + tazobactam and amikacin (OR – 17.01, 95% CI 2.41–120.23) (LOE IV, GOR C).3
  A RCT reported a prolonged infusion (4 hours) of meropenem (20 mg/kg/dose every 8 hours and 40 mg/kg/dose every 8 hours in meningitis and Pseudomonas infection) in 102 neonates with gram-negative late onset infection is associated with higher rate of clinical improvement, microbiologic eradication, less neonatal mortality (14% versus 31%; p=0.03), shorter duration of respiratory support and less acute kidney injury compared with the conventional strategy (30 minute infusion) [LOE II GOR B].5
  Pharmacokinetics:
  Meropenem is primarily excreted via the kidneys.
  Meropenem clearance is influenced by serum creatinine and postmenstrual age in neonates.2
  A comparative pharmacokinetic study of short (30 minute) versus long (4 hour) infusion in neonates showed short infusion resulted in a higher mean drug concentration in serum (C(max)) than a prolonged infusion.6 However, a longer infusion may have greater efficacy.5
  There is a knowledge gap in pharmacokinetic (PK) studies of neonates with renal impairment.2,3
  However, dose adjustment for renal failure may not be appropriate in cases where severe sepsis is probably responsible for acute renal failure [expert opinion].
  Dose:
  Multicentre, prospective PK study conducted in USA suggested a dosing strategy of 20 mg/kg every 12 hours in infants < 32 weeks GA and PNA < 14 days; 20 mg/kg every 8 hours in infants < 32 weeks GA and PNA ≥ 14 days and in infants ≥ 32 weeks GA and PNA < 14 days; and 30 mg/kg every 8 hours in infants ≥ 32 weeks GA and PNA ≥ 14 days to achieve therapeutic concentrations in infants with suspected intra-abdominal infections.4
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  Practice points
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  References
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  Pacifici GM, Allegaert K. Clinical pharmacology of carbapenems in neonates. J Chemother 2014;26(2):67–73.
  Vardakas KZ, Tansarli GS, Rafailidis PI, Falagas ME. Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum beta-lactamases: a systematic review and meta-analysis. J Antimicrob Chemother 2012;67(12):2793–803.
  Velaphi S, Wadula J, Nakwa F. Mortality rate in neonates infected with extended-spectrum b-lactamase-producing Klebsiella species and selective empirical use of meropenem. Ann Trop Paediatr 2009;29:101–10.
  Smith PB, Cohen-Wolkowiez M, Castro LM, Poindexter B, Bidegain M, Weitkamp JH, et al, Meropenem Study Team. Population pharmacokinetics of meropenem in plasma and cerebrospinal fluid of infants with suspected or complicated intra-abdominal infections. Pediatr Infect Dis J 2011;30(10):844–9.
  Shabaan AE, Nour I, Elsayed Eldegla H, Nasef N, Shouman B, Abdel-Hady H. Conventional Versus Prolonged Infusion of Meropenem in Neonates With Gram-negative Late-onset Sepsis: A Randomized Controlled Trial. Pediatric Infectious Disease Journal. 2017;36:358-63.
  Padari H, Metsvaht T, Korgvee LT, Germovsek E, Ilmoja ML, Kipper K, Herodes K, Standing JF, Oselin K, Lutsar I. Short versus long infusion of meropenem in very-low-birth-weight neonates. Antimicrob Agents Chemother 2012;56(9):4760–4.
  Micromedex online. Accessed on 14 October 2017.
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  Original version Date: 05/12/2015
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  Author: NMF Consensus Group
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  Current Version number: 3
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  Version Date: 11/12/2020
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  Risk Rating: Low
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  Due for Review: 11/12/2025
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  Approved by: DTC
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  Approval Date: TBA
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