BNF for Children 2011-2012

272 5.1.2 Cephalosporins, carbapenems, and other beta-lactams BNFC 2011–20125 Infections5.1.2.2 CarbapenemsThe carbapenems are beta-lactam antibacterials with abroad-spectrum of activity which includes many Grampositiveand Gram-negative bacteria, and anaerobes;imipenem and meropenem have good activity againstPseudomonas aeruginosa. The carbapenems are notactive against meticillin-resistant Staphylococcus aureusand Enterococcus faecium.Imipenem and meropenem are used for the treatment ofsevere hospital-acquired infections and polymicrobialinfections caused by multiple-antibacterial resistantorganisms (including septicaemia, hospital-acquiredpneumonia, intra-abdominal infections, skin and softtissueinfections, and complicated urinary-tract infections).Ertapenem is licensed for treating abdominal andgynaecological infections and for community-acquiredpneumonia, but it is not active against atypical respiratorypathogens and it has limited activity against penicillin-resistantpneumococci. Unlike the other carbapenems,ertapenem is not active against Pseudomonas oragainst Acinetobacter spp.Imipenem is partially inactivated in the kidney by enzymaticactivity and is therefore administered in combinationwith cilastatin, a specific enzyme inhibitor, whichblocks its renal metabolism. Meropenem and ertapenemare stable to the renal enzyme which inactivates imipenemand therefore can be given without cilastatin.Side-effects of imipenem with cilastatin are similar tothose of other beta-lactam antibiotics; neurotoxicity hasbeen observed at very high dosage, in renal failure, or inpatients with CNS disease. Meropenem has less seizureinducingpotential and can be used to treat centralnervous system infection. Ertapenem has been associatedwith seizures uncommonly.ERTAPENEMCautions hypersensitivity to beta-lactam antibacterials(avoid if history of immediate hypersensitivityreaction, see also p. 257); renal impairment, CNSdisorders—risk of seizures; interactions: Appendix 1(ertapenem)Renal impairment risk of seizures; avoid if estimatedglomerular filtration rate less than 30 mL/minute/1.73 m 2Pregnancy manufacturer advises avoid unless potentialbenefit outweighs riskBreast-feeding present in milk—manufactureradvises avoidSide-effects diarrhoea, nausea, vomiting, headache,injection-site reactions, rash (also reported witheosinophilia and systemic symptoms), pruritus, raisedplatelet count; less commonly dry mouth, taste disturbances,dyspepsia, abdominal pain, anorexia, constipation,melaena, antibiotic-associated colitis,bradycardia, hypotension, chest pain, oedema, pharyngealdiscomfort, dyspnoea, dizziness, sleep disturbances,confusion, asthenia, seizures, raised glucose,petechiae; rarely dysphagia, cholecystitis, liver disorder(including jaundice), arrhythmia, increase in bloodpressure, syncope, nasal congestion, cough, wheezing,anxiety, depression, agitation, tremor, pelvicperitonitis, renal impairment, muscle cramp, scleraldisorder, blood disorders (including neutropenia,thrombocytopenia, haemorrhage), hypoglycaemia,electrolyte disturbances; also reported hallucinations,dyskinesiaIndication and doseAbdominal infections, acute gynaecologicalinfections, community-acquired pneumonia. By intravenous infusionChild 3 months–13 years 15 mg/kg every 12hours (max. 1 g daily)Child 13–18 years 1 g once dailyAdministration reconstitute 1 g with 10 mL Water forInjections or Sodium Chloride 0.9%; for intermittentintravenous infusion, dilute requisite dose in SodiumChloride 0.9% to a final concentration not exceeding20 mg/mL; incompatible with glucose solutionsInvanz c (MSD) AIntravenous infusion, powder for reconstitution,ertapenem (as sodium salt), net price 1-g vial = £31.65Electrolytes Na + 6 mmol/1-g vialIMIPENEM WITH CILASTATINCautions CNS disorders (e.g. epilepsy); hypersensitivityto beta-lactam antibacterials (avoid if history ofimmediate hypersensitivity reaction, see also p. 257);interactions: Appendix 1 (imipenem with cilastatin)Renal impairment reduce dose if estimated glomerularfiltration rate less than 70 mL/minute/1.73 m 2 ;risk of CNS side-effectsPregnancy manufacturer advises avoid unless potentialbenefit outweighs risk (toxicity in animal studies)Breast-feeding present in milk but unlikely to beabsorbed (however, manufacturer advises avoid)Side-effects nausea, vomiting, diarrhoea (antibioticassociatedcolitis reported), taste disturbances, toothor tongue discoloration, hearing loss; blood disorders,positive Coombs’ test; allergic reactions (with rash,pruritus, urticaria, Stevens-Johnson syndrome, fever,anaphylactic reactions, rarely toxic epidermal necrolysis,exfoliative dermatitis); myoclonic activity, convulsions,confusion and mental disturbances reported;slight increases in liver enzymes and bilirubinreported, rarely hepatitis; increases in serum creatinineand blood urea; red coloration of urine in childrenreported; local reactions: erythema, pain andinduration, and thrombophlebitisLicensed use not licensed for use in children under 3months; not licensed for use in children with renalimpairmentIndication and doseAerobic and anaerobic Gram-positive andGram-negative infections, hospital-acquiredsepticaemia Table 1, section 5.1; not indicated forCNS infections. By intravenous infusionexpressed in terms of imipenemNeonate under 7 days 20 mg/kg every 12 hoursNeonate 7–21 days 20 mg/kg every 8 hoursNeonate 21–28 days 20 mg/kg every 6 hoursChild 1–3 months 20 mg/kg every 6 hours