title: Multidrug-Resistant Gram-Negative Bacterial Infections in the Hospital Setting: Overview, Implications for Clinical Practice, and Emerging Treatment Options.
abstract: The increasing prevalence of infections due to multidrug-resistant (MDR) gram-negative bacteria constitutes a serious threat to global public health due to the limited treatment options available and the historically slow pace of development of new antimicrobial agents. Infections due to MDR strains are associated with increased morbidity and mortality and prolonged hospitalization, which translates to a significant burden on healthcare systems. In particular, MDR strains of Enterobacteriaceae (especially Klebsiella pneumoniae and Escherichia coli), Pseudomonas aeruginosa, and Acinetobacter baumannii have emerged as particularly serious concerns. In the United States, MDR strains of these organisms have been reported from hospitals throughout the country and are not limited to a small subset of hospitals. Factors that have contributed to the persistence and spread of MDR gram-negative bacteria include the following: overuse of existing antimicrobial agents, which has led to the development of adaptive resistance mechanisms by bacteria; a lack of good antimicrobial stewardship such that use of multiple broad-spectrum agents has helped perpetuate the cycle of increasing resistance; and a lack of good infection control practices. The rising prevalence of infections due to MDR gram-negative bacteria presents a significant dilemma in selecting empiric antimicrobial therapy in seriously ill hospitalized patients. A prudent initial strategy is to initiate treatment with a broad-spectrum regimen pending the availability of microbiological results allowing for targeted or narrowing of therapy. Empiric therapy with newer agents that exhibit good activity against MDR gram-negative bacterial strains such as tigecycline, ceftolozane-tazobactam, ceftazidime-avibactam, and others in the development pipeline offer promising alternatives to existing agents.
authors: 1 Division of Hospital Medicine, Cooper Medical School of Rowan University , Camden, New Jersey.
authors: Elizabeth
authors: E
authors: Cerceo
authors: 2 Department of Hospital Medicine, Ochsner Clinical School, Ochsner Health Center , New Orleans, Louisiana.
authors: Steven B
authors: SB
authors: Deitelzweig
authors: 3 Department of Medicine, Glen Cove Hospital , Glen Cove, New York.
authors: Bradley M
authors: BM
authors: Sherman
authors: 4 Department of Medicine, University of California , Irvine, California.
authors: Alpesh N
authors: AN
authors: Amin
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects / Q000502:physiology; D004359:Drug Therapy, Combination; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D006573:Heterocyclic Compounds, 1-Ring / Q000627:therapeutic use; D006761:Hospitals; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D000077731:Meropenem; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D012853:Sisomicin / Q000031:analogs & derivatives / Q000627:therapeutic use; D013754:Tetracyclines / Q000627:therapeutic use; D013845:Thienamycins / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D001897:Boronic Acids; D006573:Heterocyclic Compounds, 1-Ring; C000599945:RPX7009; D013754:Tetracyclines; D013845:Thienamycins; C571179:eravacycline; D000077731:Meropenem; C550938:plazomicin; D012853:Sisomicin