SUMMARY: Gram-negative organisms comprise a large portion of the pathogens responsible for lower respiratory tract infections, especially those that are nosocomially acquired, and the rate of antibiotic resistance among these organisms continues to rise. Systemically administered antibiotics used to treat these infections often have poor penetration into the lung parenchyma and narrow therapeutic windows between efficacy and toxicity. The use of inhaled antibiotics allows for maximization of target site concentrations and optimization of pharmacokinetic/pharmacodynamic indices while minimizing systemic exposure and toxicity. This review is a comprehensive discussion of formulation and drug delivery aspects, in vitro and microbiological considerations, pharmacokinetics, and clinical outcomes with inhaled antibiotics as they apply to disease states other than cystic fibrosis. In reviewing the literature surrounding the use of inhaled antibiotics, we also highlight the complexities related to this route of administration and the shortcomings in the available evidence. The lack of novel anti-Gram-negative antibiotics in the developmental pipeline will encourage the innovative use of our existing agents, and the inhaled route is one that deserves to be further studied and adopted in the clinical arena.

Metallo-β-lactamase (MBL)-producing Enterobacteriaceae , particularly those that coharbor serine β-lactamases, are a serious emerging public health threat given their rapid dissemination and the limited number of treatment options. Preclinical and anecdotal clinical data support the use of aztreonam in combination with ceftazidime-avibactam against these pathogens, but other aztreonam-based combinations have not been explored.

Antimicrobial susceptibility testing (AST) is a critical function of the clinical microbiology laboratory and is essential for optimizing care of patients with infectious diseases, monitoring antimicrobial resistance (AMR) trends, and informing public health initiatives. Several methods are available for performing AST including broth microdilution, agar dilution, and disk diffusion. Technological advances such as the development of commercial automated susceptibility testing platforms and the advent of rapid diagnostic tests have improved the rapidity, robustness, and clinical application of AST. Numerous accrediting and regulatory agencies are involved in the process of AST and setting and revising breakpoints, including the U.S. Food and Drug Administration and the Clinical and Laboratory Standards Institute. Challenges to optimizing AST include the emergence of new resistance mechanisms, the development of new antimicrobial agents, and generation of new data requiring updates and revisions to established methods and breakpoints. Together, the challenges in AST methods and their interpretation create important opportunities for well‐informed clinicians to improve patient outcomes and provide value to antimicrobial stewardship programs, especially in the setting of rapidly changing and increasing AMR. Addressing AST challenges will involve continued development of new technologies along with collaboration between clinicians and the laboratory to facilitate optimal antimicrobial use, combat the increasing burden of AMR, and inform the development of novel antimicrobials. This updated primer serves to reinforce important principles of AST, and to provide guidance on their implementation and optimization.

Klebsiella pneumoniae can cause severe infections in the blood, urinary tract, and lungs. Resistance to carbapenems in K. pneumoniae is an urgent public health threat, since it can make these isolates difficult to treat.