Emergence of resistance to multiple antimicrobial agents in pathogenic bacteria has become a significant public health threat as there are fewer, or even sometimes no, effective antimicrobial agents available for infections caused by these bacteria. Gram-positive and Gram-negative bacteria are both affected by the emergence and rise of antimicrobial resistance. As this problem continues to grow, harmonized definitions with which to describe and classify bacteria that are resistant to multiple antimicrobial agents are needed, so that epidemiological surveillance data can be reliably collected and compared across healthcare settings and countries. In the strictest sense, multidrug-resistant organisms (MDROs) are labelled as such because of their in vitro resistance to more than one antimicrobial agent. Infections with MDROs can lead to inadequate or delayed antimicrobial therapy, and are associated with poorer patient outcomes [ 1 x 1 Anderson, DJ, Engemann, JJ, Harrell, LJ, Carmeli, Y, Reller, LB, and Kaye, KS. Predictors of mortality in patients with bloodstream infection due to ceftazidime‐resistant Klebsiella pneumoniae. Antimicrob Agents Chemother. 2006; 50: 1715–1720 Crossref | PubMed | Scopus (58) | Google Scholar See all References , 2 x 2 Cosgrove, SE, Sakoulas, G, Perencevich, EN, Schwaber, MJ, Karchmer, AW, and Carmeli, Y. Comparison of mortality associated with methicillin‐resistant and methicillin‐susceptible Staphylococcus aureus bacteremia: a meta‐analysis. Clin Infect Dis. 2003; 36: 53–59 Crossref | PubMed | Scopus (1301) | Google Scholar See all References , 3 x 3 Roberts, RR, Hota, B, Ahmad, I et al. Hospital and societal costs of antimicrobial‐resistant infections in a Chicago teaching hospital: implications for antibiotic stewardship. Clin Infect Dis. 2009; 49: 1175–1184 Crossref | PubMed | Scopus (332) | Google Scholar See all References , 4 x 4 Ibrahim, EH, Sherman, G, Ward, S, Fraser, VJ, and Kollef, MH. The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest. 2000; 118: 146–155 Crossref | PubMed | Scopus (1330) | Google Scholar See all References ]. Of the MDROs, highly-resistant Gram-negative bacteria (e.g. multi-drug-resistant carbapenemase-producing Klebsiella pneumoniae and Acinetobacter spp.) require special mention; these organisms can be resistant to all currently available antimicrobial agents or remain susceptible only to older, potentially more toxic agents such as the polymyxins, leaving limited and suboptimal options for treatment [ 5 x 5 McGowan, JJE. Resistance in nonfermenting gram‐negative bacteria: multidrug resistance to the maximum. Am J Med. 2006; 119: 29–36 Abstract | Full Text | Full Text PDF | PubMed | Scopus (106) | Google Scholar See all References , 6 x 6 Bonomo, RA and Szabo, D. Mechanisms of multidrug resistance in Acinetobacter species and Pseudomonas aeruginosa. Clin Infect Dis. 2006; 43: 49–56 Crossref | PubMed | Scopus (379) | Google Scholar See all References , 7 x 7 Pitout, JDD and Laupland, KB. Extended‐spectrum [beta]‐lactamase‐producing Enterobacteriaceae: an emerging public‐health concern. Lancet Infect Dis. 2008; 8: 159–166 Abstract | Full Text | Full Text PDF | PubMed | Scopus (1050) | Google Scholar See all References ]. The problem of increasing antimicrobial resistance is even more threatening when considering the very limited number of new antimicrobial agents that are in development [ 8 x 8 European Centre for Disease Prevention and Control/European Medicines Agency. ECDC/EMEA joint technical report: the bacterial challenge: time to react.: European centre for disease prevention and control & European medicines agency, Stockholm, Sweden & London, United Kingdom, 2009. Google Scholar See all References , 9 x 9 Boucher, HW, Talbot, GH, Bradley, JS et al. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis. 2009; 48: 1–12 Crossref | PubMed | Scopus (2341) | Google Scholar See all References ].

SUMMARY: Acinetobacter baumannii has emerged as a highly troublesome pathogen for many institutions globally. As a consequence of its immense ability to acquire or upregulate antibiotic drug resistance determinants, it has justifiably been propelled to the forefront of scientific attention. Apart from its predilection for the seriously ill within intensive care units, A. baumannii has more recently caused a range of infectious syndromes in military personnel injured in the Iraq and Afghanistan conflicts. This review details the significant advances that have been made in our understanding of this remarkable organism over the last 10 years, including current taxonomy and species identification, issues with susceptibility testing, mechanisms of antibiotic resistance, global epidemiology, clinical impact of infection, host-pathogen interactions, and infection control and therapeutic considerations.

SUMMARY: Extended-spectrum β-lactamases (ESBLs) are a rapidly evolving group of β-lactamases which share the ability to hydrolyze third-generation cephalosporins and aztreonam yet are inhibited by clavulanic acid. Typically, they derive from genes for TEM-1, TEM-2, or SHV-1 by mutations that alter the amino acid configuration around the active site of these β-lactamases. This extends the spectrum of β-lactam antibiotics susceptible to hydrolysis by these enzymes. An increasing number of ESBLs not of TEM or SHV lineage have recently been described. The presence of ESBLs carries tremendous clinical significance. The ESBLs are frequently plasmid encoded. Plasmids responsible for ESBL production frequently carry genes encoding resistance to other drug classes (for example, aminoglycosides). Therefore, antibiotic options in the treatment of ESBL-producing organisms are extremely limited. Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have recently been reported. ESBL-producing organisms may appear susceptible to some extended-spectrum cephalosporins. However, treatment with such antibiotics has been associated with high failure rates. There is substantial debate as to the optimal method to prevent this occurrence. It has been proposed that cephalosporin breakpoints for theEnterobacteriaceaeshould be altered so that the need for ESBL detection would be obviated. At present, however, organizations such as the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) provide guidelines for the detection of ESBLs in klebsiellae andEscherichia coli. In common to all ESBL detection methods is the general principle that the activity of extended-spectrum cephalosporins against ESBL-producing organisms will be enhanced by the presence of clavulanic acid. ESBLs represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic resistance mechanisms in the face of the introduction of new antimicrobial agents.

This document presents guidelines for developing institutional programs to enhance antimicrobial stewardship, an activity that includes appropriate selection, d

Combination antiretroviral therapy with protease inhibitors has transformed HIV infection from a terminal condition into one that is manageable. However, the complexity of regimens makes adherence to therapy difficult. To assess the effects of different levels of adherence to therapy on virologic, immunologic, and clinical outcome; to determine modifiable conditions associated with suboptimal adherence; and to determine how well clinicians predict patient adherence. Prospective, observational study. HIV clinics in a Veterans Affairs medical center and a university medical center. 99 HIV-infected patients who were prescribed a protease inhibitor and who neither used a medication organizer nor received their medications in an observed setting (such as a jail or nursing home). Adherence was measured by using a microelectronic monitoring system. The adherence rate was calculated as the number of doses taken divided by the number prescribed. Patients were followed for a median of 6 months (range, 3 to 15 months). During the study period, 45 397 doses of protease inhibitor were monitored in 81 evaluable patients. Adherence was significantly associated with successful virologic outcome (P < 0.001) and increase in CD4 lymphocyte count (P = 0.006). Virologic failure was documented in 22% of patients with adherence of 95% or greater, 61% of those with 80% to 94.9% adherence, and 80% of those with less than 80% adherence. Patients with adherence of 95% or greater had fewer days in the hospital (2.6 days per 1000 days of follow-up) than those with less than 95% adherence (12.9 days per 1000 days of follow-up; P = 0.001). No opportunistic infections or deaths occurred in patients with 95% or greater adherence. Active psychiatric illness was an independent risk factor for adherence less than 95% (P = 0.04). Physicians predicted adherence incorrectly for 41% of patients, and clinic nurses predicted it incorrectly for 30% of patients. Adherence to protease inhibitor therapy of 95% or greater optimized virologic outcome for patients with HIV infection. Diagnosis and treatment of psychiatric illness should be further investigated as a means to improve adherence to therapy.