with a carbapenem in patients with sepsis. In 2015, the National Institute for Health and Care Excellence recommended piperacillin-tazobactam as first line therapy for the treatment of bloodstream infections in neutropenic cancer patients. For bloodstream infections known to be due to extended spectrum beta-lactamase producing Enterobacteriaceace, carbapenems are superior to alternative treatments. Spectrum of activity Carbapenems exhibit broad spectrum activity against gram-negative bacteria and somewhat narrower activity against gram-positive bacteria. For empiric therapy treatment of infections prior to identification of the responsible pathogen) they are often combined with a second drug having broader spectrum gram-positive activity. Gram-negative pathogens The spectrum of activity of the carbapenems imipenem, doripenem, and meropenem includes most Enterobacteriaceace species, including Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii, Proteus mirabilis, and Serratia marcescens. Activity is maintained against most strains of E. coli and K. pneumoniae that are resistant to cephalosporins due to the production of extended spectrum beta-lactamases. Imipenem, doripenem, and meropenem also exhibit good activity against most strains of Pseudomonas aeruginosa and Acinetobacter species. The observed activity against these pathogens is especially valued as they are intrinsically resistant to many other antibiotic classes. Gram-positive pathogens The spectrum of activity of the carbapenems against gram-positive bacteria is fairly broad, but not as exceptionally so as in the case of gram-negative bacteria. Good activity is seen against methicillin-sensitive strains of Staphylococcus species, but many other antibiotics provide coverage for such infections. Good activity is also observed for most Streptococcus species, including penicillin-resistant strains. Carbapenems are not highly active against methicillin-resistant Staphylococcus aureus or most enterococcal infections because carbapenems do not bind to the penicillin-binding protein used by these pathogens. Other Carbapenems generally exhibit good activity against anaerobes such as Bacteroides fragilis. Like other beta lactam antibiotics, they lack activity against atypical bacteria, which do not have a cell wall and are thus not affected by cell wall synthesis inhibitors. Contraindications Carbapenems are contraindicated in patients with prior allergic reactions to beta lactam antibiotics. In addition, as the intramuscular formulations of ertapenem and imipenem are formulated with lidocaine, the intramuscular formulation of these two drugs are contraindicated in patients with prior adverse reactions to lidocaine. Furthermore, carbapenems are also contraindicated in patients who are taking valproic acid for seizures, as it has been shown to decrease valproic acid concentrations by as much as 90%. Adverse effects Serious and occasionally fatal allergic reactions can occur in people treated with