Antibiotic resistance, and, in a broader perspective, antimicrobial resistance (AMR), continues to evolve and spread beyond all boundaries. As a result, infectious diseases have become more challenging or even impossible to treat, leading to an increase in morbidity and mortality. Despite the failure of conventional, traditional antimicrobial therapy, in the past two decades, no novel class of antibiotics has been introduced. Consequently, several novel alternative strategies to combat these (multi-) drug-resistant infectious microorganisms have been identified. The purpose of this review is to gather and consider the strategies that are being applied or proposed as potential alternatives to traditional antibiotics. These strategies include combination therapy, techniques that target the enzymes or proteins responsible for antimicrobial resistance, resistant bacteria, drug delivery systems, physicochemical methods, and unconventional techniques, including the CRISPR-Cas system. These alternative strategies may have the potential to change the treatment of multi-drug-resistant pathogens in human clinical settings.

Surveillance of antimicrobial agent resistance provides important information to guide microbiologists and infectious disease specialists understanding of the control and the spread of resistance mechanisms within the local environment. Continued monitoring of antimicrobial resistance patterns in the community and in local hospital environments is essential to guide effective empiric therapy. The Study for Monitoring Antimicrobial Resistance Trends (SMART) has monitored the in vitro susceptibility patterns of clinical Gram-negative bacilli to antimicrobial agents collected worldwide from intra-abdominal infections since 2002 and urinary tract infections since 2009. Resistance trends, with a particular focus on carbapenem resistance and the rate of extended-spectrum β-lactamases (ESBLs), were analyzed. Isolates from intra-abdominal infections (n = 92,086) and urinary-tract infections (n = 24,705) were collected and tested using Clinical and Laboratory Standards Institute methods. This review presents carbapenem susceptibility and ESBL rates over ten years of SMART study analysis, including key publications during this period. The SMART study has proved to be a valuable resource in determining pathogen prevalence and antibiotic susceptibility over the last ten years and continues to provide evidence for regulatory susceptibility breakpoints and clinical decision making.

Of 3,004 gram-negative bacilli collected from intra-abdominal infections in the Asia-Pacific region during 2007, 42.2% and 35.8% ofEscherichia coliandKlebsiellaspp., respectively, were extended-spectrum β-lactamase (ESBL) positive. Moreover ESBL rates in India forE. coli,Klebsiella pneumoniae, andKlebsiella oxytocawere 79.0%, 69.4%, and 100%, respectively. ESBL-positiveE. colirates were also relatively high in China (55.0%) and Thailand (50.8%). Ertapenem and imipenem were the most active drugs tested, inhibiting over 90% of all species, including ESBL-positive isolates with the exception ofPseudomonas aeruginosaisolates (<90% susceptible to all study drugs) and ESBL-positiveKlebsiella pneumoniaeisolates (<90% susceptible to all study drugs except imipenem). Quinolones achieved 90% inhibition levels only against ESBL-negativeK. pneumoniaeand ESBL-negativeK. oxytoca. A decline in ampicillin-sulbactam activity was noted, with only 34.5% of allEnterobacteriaceaeinhibited in this study.

From 2002 to 2008, there was a significant increase in extended-spectrum beta-lactamase (ESBL)-positive Escherichia coli isolates in European intra-abdominal infections, from 4.3% in 2002 to 11.8% in 2008 ( P < 0.001), but not for ESBL-positive Klebsiella pneumoniae isolates (16.4% to 17.9% [ P > 0.05]). Hospital-associated isolates were more common than community-associated isolates, at 14.0% versus 6.5%, respectively, for E. coli ( P < 0.001) and 20.9% versus 5.3%, respectively, for K. pneumoniae ( P < 0.01). Carbapenems were consistently the most active drugs tested.