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    Treating UTIs in the age of antibiotic resistance: Strategies for the practicing OB/GYN

     

    Carbapenem resistance

    Of great concern is that antibiotic resistance to the carbapenems has also been recently reported. K pneumoniae carbapenemase (KPC) was first identified in 1996 as a beta-lactamase enzyme capable of inactivating the carbapenem class of antibiotics, along with penicillins and cephalosporins.18 Carbapenems enter gram-negative organisms through outer membrane proteins known as porins and inactivate the enzymes needed for peptidoglycan cross-linking, ultimately causing cell death. Resistance to carbapenems can also develop either by loss of these outer membrane porin channels, or by modifications of the penicillin-binding proteins, so that they do not bind with the carbapenems.18 A recent article by Khari et al highlights the challenges in treating KPC-producing K pneumoniae-associated pyelonephritis in pregnancy, which they managed with a prolonged course of an extended-infusion cefepime and oral fosfomycin.19

    To meet this challenge, a new option in treatment of these MDR gram-negative infections has been the combination of a new beta-lactamase inhibitor, avibactam, combined with a third-generation cephalosporin, ceftazidime. Ceftazidime-avibactam, marketed as Avycaz, demonstrates greater resistance to beta-lactamases produced by MDR pathogens, including some KPC-producing organisms. Avibactam has greater activity than other beta-lactamase inhibitors, such as clavulanic acid, sulbactam, and tazobactam.20,21 Ceftazidime-avibactam is approved for complicated UTIs including pyelonephritis and is given at a dose of 2.5 g IV q 8 hrs for 7 to 14 days. Combinations of avibactam with other beta-lactam antibiotics are in development and may provide additional options in the treatment of MDRO infections. Lastly, investigators are reevaluating the use of colistin, of the polymyxin class of antibiotics, originally used in the 1950s. These antibiotics cause cell death by disrupting the gram-negative cell membrane.22 While they were discontinued due to concerns of nephrotoxicity and due to the development of safer antibiotics, this class of antibiotic is being reintroduced in cases of extensive gram-negative resistance.

    An additional concern is that, as patients develop colonization with resistant organisms, this may affect commonly used treatment regimens for conditions such as intra-amniotic infection and postpartum endometritis, in which therapy is often started empirically with combined penicillin, gentamicin, and clindamycin/metronidazole in the absence of genital cultures. The need for organism identification will become more pressing as resistance to our commonly used antibiotics regimens increases, with delay in starting appropriate therapy resulting in increased morbidity.

     

    Christopher Hicks, MD
    Dr Hicks is Resident in the Department of Obstetrics and Gynecology, Bridgeport Hospital, Bridgeport, Connecticut.
    Zane Saul, MD
    Dr Saul is Chief, Section of Infectious Disease, Department of Internal Medicine, Bridgeport Hospital, Bridgeport, Connecticut, and ...

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