The first consensus guideline for therapeutic monitoring of vancomycin in adult patients was published in 2009. A committee representing 3 organizations (the American Society for Health-System Pharmacists [ASHP], Infectious Diseases Society of America [IDSA], and Society for Infectious Diseases Pharmacists [SIDP]) searched and reviewed all relevant peer-reviewed data on vancomycin as it related to in vitro and in vivo pharmacokinetic and pharmacodynamic (PK/PD) characteristics, including information on clinical efficacy, toxicity, and vancomycin resistance in relation to serum drug concentration and monitoring. The data were summarized, and specific dosing and monitoring recommendations were made. The primary recommendations consisted of eliminating routine monitoring of serum peak concentrations, emphasizing a ratio of area under the curve over 24 hours to minimum inhibitory concentration (AUC/MIC) of ≥400 as the primary PK/PD predictor of vancomycin activity, and promoting serum trough concentrations of 15 to 20 mg/L as a surrogate marker for the optimal vancomycin AUC/MIC if the MIC was ≤1 mg/L in patients with normal renal function. The guideline also recommended, albeit with limited data support, that actual body weight be used to determine the vancomycin dosage and loading doses for severe infections in patients who were seriously ill.¹

Practice guidelines for therapeutic monitoring of vancomycin treatment for Staphylococcus aureus infection in adult patients were reviewed by an expert panel of the Infectious Diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists. A literature review of existing evidence regarding vancomycin dosing and monitoring of serum concentrations, in addition to patient outcomes combined with expert opinion regarding the drug's pharmacokinetic, pharmacodynamic, and safety record, resulted in new recommendations for targeting and adjustment of vancomycin therapy.

Vancomycin is one of only a few antibiotics available to treat patients infected with methicillin-resistant Staphylococcus aureus and methicillin-res

Increasing antimicrobial resistance and medical device-related infections have led to a renewed interest in phage therapy as an alternative or adjunct to conventional antimicrobials. Expanded access and compassionate use cases have risen exponentially but have varied widely in approach, methodology, clinical situations in which phage therapy might be considered, dosing, route of administration, and outcomes.

Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa isolates are frequent causes of serious nosocomial infections that may compromise the selection of antimicrobial therapy. The goal of this review is to summarize recent epidemiologic, microbiologic, and clinical data pertinent to the therapeutic management of patients with infections caused by MDR/XDR-P. aeruginosa. Historically, conventional antipseudomonal β-lactam antibiotics have been used for the empiric treatment of MDR/XDR-P. aeruginosa. Owing to the remarkable capacity of P. aeruginosa to confer resistance via multiple mechanisms, these traditional therapies are often rendered ineffective. To increase the likelihood of administering empiric antipseudomonal therapy with in vitro activity, a second agent from a different antibiotic class is often administered concomitantly with a traditional antipseudomonal β-lactam. However, combination therapy may pose an increased risk of antibiotic toxicity and secondary infection, notably, Clostridioides difficile. Multiple novel agents that demonstrate in vitro activity against MDR-P. aeruginosa (e.g., β-lactam/β-lactamase inhibitor combinations and cefiderocol) have been recently granted US Food and Drug Administration (FDA) approval and are promising additions to the antipseudomonal armamentarium. Even so, comparative clinical data pertaining to these novel agents is sparse, and concerns surrounding the scarcity of antibiotics active against refractory MDR/XDR-P. aeruginosa necessitates continued assessment of alternative therapies. This is particularly important in patients with cystic fibrosis (CF) who may be chronically colonized and suffer from recurrent infections and disease exacerbations due in part to limited efficacious antipseudomonal agents. Bacteriophages represent a promising candidate for combatting recurrent and refractory infections with their ability to target specific host bacteria and circumvent traditional mechanisms of antibiotic resistance seen in MDR/XDR-P. aeruginosa. Future goals for the management of these infections include increased comparator clinical data of novel agents to determine in what scenario certain agents may be preferred over others. Until then, appropriate treatment of these infections requires a thorough evaluation of patient- and infection-specific factors to guide empiric and definitive therapeutic decisions.

We evaluated the impact of high (9.5 log₁₀CFU/g) and moderate (5.5 log₁₀CFU/g) inocula of methicillin-susceptible and -resistant Staphylococcus aureus(MSSA and MRSA, respectively) on the activities of nafcillin, linezolid, vancomycin, and daptomycin, alone and in combination with gentamicin in an in vitro pharmacodynamic model with simulated endocardial vegetations over 72 h. Human therapeutic dosing regimens for nafcillin, daptomycin, vancomycin, linezolid, and gentamicin were simulated. At a moderate inoculum, nafcillin (MSSA only), vancomycin, and daptomycin demonstrated equivalent and significant (P< 0.01) bactericidal (99.9% kill) activities (decreases of 3.34 ± 1.1, 3.28 ± 0.4, and 3.34 ± 0.8 log₁₀CFU/g, respectively). Bactericidal activity was demonstrated at 4 h for nafcillin and daptomycin and at 32 h for vancomycin. Linezolid demonstrated bacteriostatic activity over the course of the study period. At a high inoculum, daptomycin exhibited bactericidal activity against both MSSA and MRSA by 24 h (decrease of 5.51 to 6.31 ± 0.10 log₁₀CFU/g). Nafcillin (versus MSSA), vancomycin, and linezolid (MSSA and MRSA) did not achieve bactericidal activity throughout the 72-h experiment. The addition of gentamicin increased the rate of 99.9% kill to 8 h for daptomycin (P< 0.01) and 48 h for nafcillin (MSSA only) (P= 0.01). The addition of gentamicin did not improve the activity of vancomycin or linezolid for either isolate for the 72-h period. Overall, high-inoculumStaphylococcus aureushad a significant impact on the activities of nafcillin and vancomycin. In contrast, daptomycin was affected minimally and linezolid was not affected by inoculum.