Aerobic gram-positive microorganisms: S. aureus including penicillinase-producing strains, Group D streptococcus including E., Streptococcus pneumoniae, S. pyogenes (Group A streptococci), S. viridans group
Aerobic gram-negative microorganisms: Acinetobacter spp., including A. calcoaceticus, Citrobacter spp., Enterobacter cloacae, E. coli, H. influenzae, K. pneumoniae, Pseudomonas aeruginosa
Anaerobic gram-positive microorganisms: Peptostreptococcus spp.
Anaerobic gram-negative microorganisms: Bacteroides spp., Fusobacterium spp.
Mechanism of Action:
Cause rapid bacterial cell death by covalently binding to penicillin-binding proteins (PBPs) involved in the biosynthesis of mucopeptides in bacterial cell walls. Bactericidal effects result through inhibition of cellular growth and division and the loss of cell wall integrity, eventually causing cell wall lysis. The primary target is PBP 2.
Carbapenems produce time-dependent killing
Cmax: 69.9mcg/ml; Half-life: 1.11 hours; Volume of distribution: 14.4L; Table 2
Hematologic: Anemia, eosinophilia, increased prothrombin time, leukopenia, myelosuppression, thrombocytopenia, and thrombocytosis
Cardiovascular System: Cardiac arrest, hypotension, tachycardia, and thrombophlebitis
Central Nervous System: Seizures, somnolence, dizziness, and vertigo
Gastrointestinal: Nausea, vomiting, oral candidiasis, pseudomembranous colitis, and taste alterations
Renal: Renal insufficiency
Hepatic: Elevated hepatic enzymes
Respiratory: Pulmonary hemorrhage, respiratory failure, hyperventilation, pulmonary infiltrates, and apnea
Dermatologic: Pruritus, urticaria, and skin rash
500mg imipenem and 500mg cilastatin power mixture for intramuscular injection
750mg imipenem and 750mg cilastatin power mixture for intramuscular injection
250mg imipenem, 250mg cilastatin, and 10mg sodium bicarbonate power mixture for intravenous injection
500mg imipenem, 500mg cilastatin, and 20mg sodium bicarbonate power mixture for intravenous injection
Mild infections: (fully susceptible) 250 mg IV every 6 hr; (moderately susceptible including P. aeruginosa) 500 mg IV every 6 hr
Moderate infections: (fully susceptible) 500 mg IV every 6-8 hr; (moderately susceptible including P. aeruginosa) 500 mg IV every 6 hr or 1 g IV every 8 hr
Severe, life-threatening infections: (fully susceptible) 500 mg IV every 6 hr; (moderately susceptible including P. aeruginosa) 1 g IV every 8 hr or 1 g IV every 6 hr; maximum 50 mg/kg/day or 4 g/day, whichever is lower
Cystic fibrosis: (12 years and older) up to 90 mg/kg/day IV divided every 6 hr; maximum 4 g/day
Urinary tract infections, uncomplicated: 250 mg IV every 6 hr
Urinary tract infections, complicated: 500 mg IV every 6 hr
Gynecologic infections: 500-750 mg IM every 12 hr
Intra-abdominal infections: 750 mg IM every 12 hr
Lower respiratory tract infections: 500-750 mg IM every 12 hr
Skin/skin structure infections: 500-750 mg IM every 12 hr
Disease state based dosing:
Renal Impairment: (IV): Table 4
Renal Impairment: (IM): Not recommended with CrCl less than 20 mL/min/1.73(2) (lack of data).
Hepatic failures: Dosage adjustment is not required.
Dosing during Continuous Renal Replacement Therapy
CVVH (Continuous venovenous hemofiltration): 250mg IV q6h OR 500mg IV q8h
CVVHD (Continuous venovenous hemodialysis): 250mg IV q6h OR 500mg IV q6-8h
CVVHDF (Continuous venovenous hemodiafiltration) 250mg IV q6h OR 500mg IV q6-8h
Note: CVVH is mainly for fluid removal alone. Many institutions will employ more CVVHD or CVVHDF which combine dialysis with fluid removal.
Contraindications: Children less than 30 kg with renal impairment, children with CNS infections (increased seizure risk), known hypersensitivity to local anesthetics of the amide type and in patients with severe shock or heart block
Precautions: History of seizures, Concomitant ganciclovir; risk for generalized seizures, Hypersensitivity to penicillins, cephalosporins, and other beta lactams
Cyclosporine (moderate severity): Neurotoxicity (mental confusion, agitation, tremor)
Ganciclovir (major severity): CNS toxicity (seizures)
Live Typhoid Vaccine (moderate severity): A decreased immunological response to the vaccine
Theophylline (major severity): Theophylline toxicity (nausea, vomiting, palpitations, seizures)
Category C: Risk unknown. Human studies inadequate.
Therapeutic: Resolution of clinical signs of infection (fever, decreased white blood cell count), Culture and sensitivity, CBC w/differential, urinalysis, temperature
Toxicity: Hepatic and renal function tests during therapy