Explore the vast range of titles available.

Antimicrobial resistance has become one of the greatest threats to public health, with rising resistance to carbapenems being a particular concern due to the lack of effective and safe alternative treatment options. Carbapenem-resistant gram-negative bacteria of clinical relevance include the Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and more recently, Stenotrophomonas maltophilia. Colistin and tigecycline have been used as first-line agents for the treatment of infections caused by these pathogens; however, there are uncertainties regarding their efficacy even when used in combination with other agents. More recently, several new agents with activity against certain carbapenem-resistant pathogens have been approved for clinical use or are reaching late-stage clinical development. They include ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, plazomicin, eravacycline, and cefiderocol. In addition, fosfomycin has been redeveloped in a new intravenous formulation. Data regarding the clinical efficacy of these new agents specific to infections caused by carbapenem-resistant pathogens are slowly emerging and appear to generally favor newer agents over previous best available therapy. As more treatment options become widely available for carbapenem-resistant gram-negative infections, the role of antimicrobial stewardship will become crucial in ensuring appropriate and rationale use of these new agents.

Fluoroquinolones have been in clinical use for over 50 years with significant efficacy. However, increasing resistance and emergence of some marked adverse events have limited their usage. The most recently approved class member, delafloxacin, is the only available anionic (non-zwitterionic) fluoroquinolone. Its unique molecular structure provides improved in vitro activity against most Gram-positive pathogens, including quinolone-resistant strains, which is further enhanced at acid pH. Delafloxacin shows favorable pharmacological properties, with about 60% bioavailability after oral administration, only mild inhibition of cytochrome P450 3A, and no evidence of cardiac- or phototoxicity in healthy volunteers (tested against positive controls). Its twice daily dosing, suitability for intravenous, oral, or switch dosing, the lack of many clinically significant drug-drug interactions, and acceptable adverse event profile in registration clinical trials supports its use in the treatment of acute bacterial skin and skin structure infections, and potentially in other infections, where resistance to other agents, safety, and/or the need for early discharge is of concern.

Imipenemase (IMP) is a metallo-β-lactamase that confers resistance to almost all β-lactams. Identification of IMP genes is essential for understanding and combatting antibiotic resistance. In this study, we report a pandrug-resistant Providencia strain from a human rectal swab. This strain carried 2 bla IMP carbapenemase genes, bla IMP-69 and bla IMP-4. IMP-69 is a novel IMP variant with an amino acid substitution at A21T compared with IMP-8. bla IMP-69 was found in a bla IMP-69-aacA4 array of an integron on a 165-kilobase (kb) IncC self-transmissible plasmid, whereas bla IMP-4 was located in a bla IMP-4-qacG-aacA4-catB3 array of an integron on a 19-kb nonself-transmissible plasmid. Such coexistence has the potential to allow the generation of new, hybrid bla IMP variants by homologous recombination. The bla IMP-69-carrying IncC plasmid belonged to the core-genome plasmid multilocus sequence typing (cgPMLST) 3.5 type. We found that cgPMLST 3.5 IncC plasmids have been circulating worldwide for decades and may represent a common vehicle mediating the spread of antimicrobial resistance.

Children living with human immunodeficiency virus (HIV) in low- and middle-income countries (LMICs) experience higher rates of virologic failure than adults. Human immunodeficiency virus drug resistance (HIVDR) plays a major role in pediatric HIV treatment failure because nonsuppressive maternal antiretroviral therapy (ART) during pregnancy and breastfeeding as well as infant antiretroviral prophylaxis lead to high rates of pretreatment drug resistance to regimens most commonly used in children living with HIV. Lack of availability of durable, potent drugs in child-friendly formulations in LMICs and adherence difficulties contribute to acquired drug resistance during treatment. Optimizing drugs available for treating children living with HIV in LMICs, providing robust adherence support, and ensuring virologic monitoring for children receiving ART are essential for reducing HIVDR and improving treatment outcomes for children living with HIV in LMICs.

Carbapenem resistance in gram-negative bacteria has caused a global epidemic that continues to grow. Although carbapenemase-producing Enterobacteriaceae have received the most attention because resistance was first reported in these pathogens in the early 1990s, there is increased awareness of the impact of carbapenem-resistant nonfermenting gram-negative bacteria, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. Moreover, evaluating the problem of carbapenem resistance requires the consideration of both carbapenemase-producing bacteria as well as bacteria with other carbapenem resistance mechanisms. Advances in rapid diagnostic tests to improve the detection of carbapenem resistance and the use of large, population-based datasets to capture a greater proportion of carbapenem-resistant organisms can help us gain a better understanding of this urgent threat and enable physicians to select the most appropriate antibiotics.

Abstract Antimicrobial resistance has become one of the greatest threats to public health, with rising resistance to carbapenems being a particular concern due to the lack of effective and safe alternative treatment options. Carbapenem-resistant gram-negative bacteria of clinical relevance include the Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and more recently, Stenotrophomonas maltophilia. Colistin and tigecycline have been used as first-line agents for the treatment of infections caused by these pathogens; however, there are uncertainties regarding their efficacy even when used in combination with other agents. More recently, several new agents with activity against certain carbapenem-resistant pathogens have been approved for clinical use or are reaching late-stage clinical development. They include ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, plazomicin, eravacycline, and cefiderocol. In addition, fosfomycin has been redeveloped in a new intravenous formulation. Data regarding the clinical efficacy of these new agents specific to infections caused by carbapenem-resistant pathogens are slowly emerging and appear to generally favor newer agents over previous best available therapy. As more treatment options become widely available for carbapenem-resistant gram-negative infections, the role of antimicrobial stewardship will become crucial in ensuring appropriate and rationale use of these new agents.

The US burden of acute skin infections is substantial. While Staphylococcus aureus and Streptococcus spp. are the most common causes, gram-negative bacteria and mixed infections can occur in some settings. These mixed infections are more likely to result in inappropriate empiric antibiotic therapy. Important challenges remain in diagnosing and treating acute skin infections.

Since its introduction in the 1990s, liposomal amphotericin B (LAmB) continues to be an important agent for the treatment of invasive fungal diseases caused by a wide variety of yeasts and molds. This liposomal formulation was developed to improve the tolerability of intravenous amphotericin B, while optimizing its clinical efficacy. Since then, numerous clinical studies have been conducted, collecting a comprehensive body of evidence on its efficacy, safety, and tolerability in the preclinical and clinical setting. Nevertheless, insights into the pharmacokinetics and pharmacodynamics of LAmB continue to evolve and can be utilized to develop strategies that optimize efficacy while maintaining the compound’s safety. In this article, we review the clinical pharmacokinetics, pharmacodynamics, safety, and efficacy of LAmB in a wide variety of patient populations and in different indications, and provide an assessment of areas with a need for further clinical research.