Aztreonam-avibactam: The dynamic duo against multidrug-resistant gram-negative pathogens.

Antimicrobial resistance poses a significant public health challenge, particularly with the rise of gram-negative hospital-acquired infections resistant to carbapenems. Aztreonam-avibactam (ATM-AVI) is a promising new combination therapy designed to combat multidrug-resistant (MDR) gram-negative bacteria, including those producing metallo-β-lactamases (MBLs). Aztreonam, a monobactam antibiotic, is resistant to hydrolysis by MBLs but can be degraded by other β-lactamases.

Heartfelt Impact: A Descriptive Analysis of Ceftaroline-Containing Regimens in Endocarditis due to Methicillin-Resistant Staphylococcus aureus.

Introduction: Infective endocarditis (IE) due to methicillin-resistant Staphylococcus aureus (MRSA) is characterized by frequent treatment failure to first-line agents and high mortality, necessitating use of alternative management strategies. Ceftaroline fosamil (CPT) is a cephalosporin antibiotic with activity against MRSA but without regulatory approval for the indication of IE. This study describes clinical experience with CPT-based regimens utilized in MRSA-IE.

Exploring synergistic and antagonistic interactions in phage-antibiotic combinations against ESKAPE pathogens.

In the era of antimicrobial resistance, phage-antibiotic combinations offer a promising therapeutic option, yet research on their synergy and antagonism is limited. This study aims to assess these interactions, focusing on protein synthesis inhibitors and cell envelope-active agents against multidrug-resistant bacterial strains. We evaluated synergistic and antagonistic interactions in multidrug-resistant , , and strains.

Antibiotic stewardship in the emergency department setting: Focus on oral antibiotic selection for adults with skin and soft tissue infections.

Purpose: An advisory panel of experts was convened by the ASHP Foundation as a part of its Medication-Use Evaluation Resources initiative to provide commentary on an approach to antibiotic stewardship in the treatment of skin and soft tissue infections (SSTIs), with a focus on oral antibiotics in the emergency department (ED) setting for patients who will be treated as outpatients. Considerations include a need to update existing guidelines to reflect new antibiotics and susceptibility patterns, patient-specific criteria impacting antibiotic selection, and logistics unique to the ED setting.

Summary: While national guidelines serve as the gold standard on which to base SSTI treatment decisions, our advisory panel stressed that institutional guidelines must be regularly updated and grounded in local antimicrobial resistance patterns, patient-specific factors, and logistical considerations.

Association between low maternal serum aflatoxin B1 exposure and adverse pregnancy outcomes in Mombasa, Kenya, 2017-2019: A nested matched case-control study.

We examined the association between serum aflatoxin B1-lysine adduct (AFB1-lys) levels in pregnant women and adverse pregnancy outcomes (low birthweight, miscarriage and stillbirth) through a nested matched case-control study of pregnant women enroled at ≤28 weeks' gestation in Mombasa, Kenya, from 2017 to 2019. Cases comprised women with an adverse birth outcome, defined as either delivery of a singleton infant weighing <2500 g, or a miscarriage, or a stillbirth, while controls were women who delivered a singleton live infant with a birthweight of ≥2500 g. Cases were matched to controls at a ratio of 1:2 based on maternal age at enrolment, gestational age at enrolment and study site.

Dalbavancin Sequential Therapy for Gram-Positive Bloodstream Infection: A Multicenter Observational Study.

Introduction: Long-acting lipoglycopeptides such as dalbavancin may have utility in patients with Gram-positive bloodstream infections (BSI), particularly in those with barriers to discharge or who require prolonged parenteral antibiotic courses. A retrospective cohort study was performed to provide further multicenter real-world evidence on dalbavancin use as a sequential therapy for Gram-positive BSI.

Methods: One hundred fifteen patients received dalbavancin with Gram-positive BSI, defined as any positive blood culture or diagnosed with infective endocarditis, from 13 centers geographically spread across the United States between July 2015 and July 2021.

Synergistic bactericidal effects of phage-enhanced antibiotic therapy against MRSA biofilms.

Unlabelled: Methicillin-resistant (MRSA) causes biofilm-related medical device infections. Phage-antibiotic combinations offer potential therapy due to proven antibiofilm efficacy. We evaluated phage-antibiotic synergy against biofilms using modified checkerboard and 24-h time-kill assays.

Phage-antibiotic synergy against daptomycin-nonsusceptible MRSA in an simulated endocardial pharmacokinetic/pharmacodynamic model.

Phage-antibiotic combinations (PAC) offer a potential solution for treating refractory daptomycin-nonsusceptible (DNS) methicillin-resistant (MRSA) infections. We examined PAC activity against two well-characterized DNS MRSA strains (C4 and C37) and . PACs comprising daptomycin (DAP) ± ceftaroline (CPT) and a two-phage cocktail (Intesti13 + Sb-1) were evaluated for phage-antibiotic synergy (PAS) against high MRSA inoculum (10 CFU/mL) using (i) modified checkerboards (CB), (ii) 24-h time-kill assays (TKA), and (iii) 168-h simulated endocardial vegetation (SEV) models.

Determining Susceptibility and Potential Mediators of Resistance for the Novel Polymyxin Derivative, SPR206, in .

With the increase in carbapenem-resistant (CRAB) infections, there has been a resurgence in the use of polymyxins, specifically colistin (COL). Since the reintroduction of COL-based regimens in treating CRAB infections, several COL-resistant isolates have been identified, with the mechanism of resistance heavily linked with the loss of the lipopolysaccharide (LPS) layer of the bacterial outer membrane through mutations in lpxACD genes or the operon. SPR206, a novel polymyxin derivative, has exhibited robust activity against multidrug-resistant (MDR) .

Cefiderocol: early clinical experience for multi-drug resistant gram-negative infections.

Multi-drug resistant gram-negative bacteria present a significant global health threat. Cefiderocol (CFDC), a siderophore cephalosporin, has shown potential in combating this threat, but with the currently available data, its role in therapy remains poorly defined. This multi-center, retrospective cohort study evaluated the real-world application of CFDC across six U.

Eravacycline, the first four years: health outcomes and tolerability data for 19 hospitals in 5 U.S. regions from 2018 to 2022.

The rise of multidrug-resistant (MDR) pathogens, especially MDR Gram-negatives, poses a significant challenge to clinicians and public health. These resilient bacteria have rendered many traditional antibiotics ineffective, underscoring the urgency for innovative therapeutic solutions. Eravacycline, a broad-spectrum fluorocycline tetracycline antibiotic approved by the FDA in 2018, emerges as a promising candidate, exhibiting potential against a diverse array of MDR bacteria, including Gram-negative, Gram-positive, anaerobic strains, and Mycobacterium.

Understanding vancomycin nephrotoxicity augmented by β-lactams: a synthesis of endosymbiosis, proximal renal tubule mitochondrial metabolism, and β-lactam chemistry.

The recent understanding that hydrophobic β-lactams have greater affinity for organic anion transporter-3 (OAT-3) of the proximal renal tubule could provide valuable insights for anticipating β-lactams that may exacerbate vancomycin-induced nephrotoxicity. Vancomycin alone provides oxidative stress on the highly metabolic proximal tubular cells. Hydrophobic β-lactams (eg, piperacillin and anti-staphylococcal β-lactams) could have greater OAT-3 mediated uptake into proximal tubular cells than hydrophilic β-lactams (eg, most cephalosporins and carbapenems), thereby causing greater mitochondrial stress on these susceptible cells.

Ciprofloxacin in combination with bacteriophage cocktails against multi-drug resistant in simulated endocardial vegetation models.

-associated infective endocarditis represents difficult-to-treat, deep-seated infections. Phage-antibiotic combinations have shown to eradicate multi-drug resistant (MDR) , limit the development of phage resistance, and restore antibiotic sensitivity. The objective of this study was to evaluate the activity of phage-ciprofloxacin (CIP) combinations in 4-day simulated endocardial vegetation (SEV) models against drug-resistant isolates.

Phage-antibiotic combinations against multidrug-resistant in static and dynamic biofilm models.

Biofilm-producing infections pose a severe threat to public health and are responsible for high morbidity and mortality. Phage-antibiotic combinations (PACs) are a promising strategy for combatting multidrug-resistant (MDR), extensively drug-resistant (XDR), and difficult-to-treat infections. Ten MDR/XDR strains and five .

Targeting Dalbavancin Inoculum Effect: Adjunctive Single Dose of Daptomycin.

Introduction: Daptomycin (DAP) has proven to be a viable alternative amid vancomycin resistance; however, the use of DAP post vancomycin treatment has led to the development of DAP non-susceptible (DNS) strains. Dalbavancin (DAL), a novel single-dosed lipoglycopeptide, has shown enhanced activity against highly resistant Staphylococcus aureus strains. However, on the basis of previous reports and our observations, DAL does not demonstrate similar activity at high versus low inoculum levels.

Long-term evaluation of clinical success and safety of omadacycline in nontuberculous mycobacteria infections: a retrospective, multicenter cohort of real-world health outcomes.

Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an aminomethylcycline antibiotic with FDA orphan drug and fast-track designations for pulmonary NTM infections, including (MAB). This multicenter retrospective study across 16 U.

Weighing the Odds: Novel β-Lactam/β-Lactamase Inhibitor Use in Hospital-Acquired and Ventilator-Associated Pneumonia for Patients Who Are Morbidly Obese.

Background: is a leading cause of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP). Novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations are often used for these infections; however, limited data exist to guide the dosing of BL/BLI in patients who are morbidly obese. Thus, we sought to evaluate the clinical and safety endpoints of patients who are morbidly obese (body mass index ≥35 kg/m) and non-morbidly obese (<35 kg/m) and receiving BL/BLI for HABP/VABP.

Colistin Monotherapy versus Combination Therapy for Carbapenem-Resistant Organisms.

Background: Pneumonia and bloodstream infections (BSI) due to extensively drug-resistant (XDR) , XDR , and carbapenem-resistant Enterobacterales (CRE) are associated with high mortality rates, and therapeutic options remain limited. This trial assessed whether combination therapy with colistin and meropenem was superior to colistin monotherapy for the treatment of these infections.

Methods: The OVERCOME (Colistin Monotherapy versus Combination Therapy) trial was an international, randomized, double-blind, placebo-controlled trial.

Phage-Antibiotic Cocktail Rescues Daptomycin and Phage Susceptibility against Daptomycin-Nonsusceptible Enterococcus faecium in a Simulated Endocardial Vegetation Model.

Enterococcus faecium is a difficult-to-treat pathogen with emerging resistance to most clinically available antibiotics. Daptomycin (DAP) is the standard of care, but even high DAP doses (12 mg/kg body weight/day) failed to eradicate some vancomycin-resistant strains. Combination DAP-ceftaroline (CPT) may increase β-lactam affinity for target penicillin binding proteins (PBP); however, in a simulated endocardial vegetation (SEV) pharmacokinetic/pharmacodynamic (PK/PD) model, DAP-CPT did not achieve therapeutic efficacy against a DAP-nonsusceptible (DNS) vancomycin-resistant E.

Evaluation of Omadacycline Alone and in Combination with Rifampin against Staphylococcus aureus and Staphylococcus epidermidis in an Pharmacokinetic/Pharmacodynamic Biofilm Model.

Biofilm-associated infections lead to substantial morbidity. Omadacycline (OMC) is a novel aminomethylcycline with potent activity against Staphylococcus aureus and Staphylococcus epidermidis, but data surrounding its use in biofilm-associated infections are lacking. We investigated the activity of OMC alone and in combination with rifampin (RIF) against 20 clinical strains of staphylococci in multiple biofilm analyses, including an pharmacokinetic/pharmacodynamic (PK/PD) CDC biofilm reactor (CBR) model (simulating human exposures).

Optimization of Phage-Antibiotic Combinations against Staphylococcus aureus Biofilms.

Phage therapy has gained attention due to the spread of antibiotic-resistant bacteria and narrow pipeline of novel antibiotics. Phage cocktails are hypothesized to slow the overall development of resistance by challenging the bacteria with more than one phage. Here, we have used a combination of plate-, planktonic-, and biofilm-based screening assays to try to identify phage-antibiotic combinations that will eradicate preformed biofilms of Staphylococcus aureus strains that are otherwise difficult to kill.

Steno-sphere: Navigating the enigmatic world of emerging multidrug-resistant Stenotrophomonas maltophilia.

Stenotrophomonas maltophilia is an opportunistic pathogen and frequent cause of serious nosocomial infections. Patient populations at greatest risk for these infections include the immunocompromised and those with chronic respiratory illnesses and prior antibiotic exposure, notably to carbapenems. Its complex virulence and resistance profile drastically limit available antibiotics, and incomplete breakpoint and pharmacokinetic/pharmacodynamic (PK/PD) data to inform dose optimization further complicates therapeutic approaches.

High-dose Cefepime vs Carbapenems for Bacteremia Caused by Enterobacterales With Moderate to High Risk of Clinically Significant AmpC β-lactamase Production.

Background: Limited data suggest that serious infections caused by Enterobacterales with a moderate to high risk of clinically significant AmpC production can be successfully treated with cefepime if the cefepime minimum inhibitory concentration (MIC) is ≤2 µg/mL. However, isolates with a cefepime-susceptible dose-dependent (SDD) MIC of 4-8 µg/mL should receive a carbapenem due to target attainment and extended-spectrum β-lactamase (ESBL) concerns.

Methods: This was a retrospective cohort study of hospitalized patients with , or bacteremia from January 2015 to March 2022 receiving high-dose cefepime or a carbapenem.