What is known and objective Treatment of methicillin‐resistant Staphylococcus aureus (MRSA) bacteraemia is a long‐standing challenge to health care, often complicated by metastatic infections, treatment failure and mortality. When MRSA bacteraemia persists despite adequate initial treatment, current Infectious Diseases Society of America guidelines recommend evaluation and removal of possible sources of infection. In addition, a change in therapy may be considered. The objective of this review was to explore the therapeutic options for the treatment of persistent MRSA bacteraemia. Methods A literature search of PubMed, MEDLINE and Google Scholar was performed using the following search terms: [methicillin‐resistant Staphylococcus aureus OR MRSA] AND [bacteraemia OR bloodstream infection] AND [persistent OR persistence OR refractory OR treatment failure OR salvage] AND treatment. We evaluated relevant, adult, English‐language, peer‐reviewed studies published between 1985 and May 2018. In vitro and animal studies were considered as supportive of in vivo data. Results and discussion Randomized, controlled trials are lacking. However, case series and case reports support multiple treatment options including high‐dose daptomycin in combination with an antistaphylococcal β‐lactam, ceftaroline, trimethoprim‐sulfamethoxazole (TMP‐SMX) or fosfomycin; ceftaroline alone or in combination with vancomycin or TMP‐SMX; linezolid alone or in combination with a carbapenem, or telavancin. What is new and conclusion Given the heterogeneity of the data, a preferred regimen has not emerged. Prescribers must take into consideration recent exposure, source control, and available synergy and clinical data. Further comparative trials are needed to establish a preferred regimen and the creation of a universal treatment algorithm.

Purpose The chemistry, pharmacokinetic and pharmacodynamic properties, efficacy, and safety of the recently introduced combination antimicrobial agent ceftolozane–tazobactam are reviewed. Summary Ceftolozane–tazobactam (Zerbaxa, Cubist Pharmaceuticals) is a cephalosporin β-lactam and β-lactamase inhibitor marketed as a fixed-dose combination agent for the treatment of complicated urinary tract and intraabdominal infections. Its dosing and chemistry provide expansive antimicrobial coverage of gram-negative organisms, including Pseudomonas aeruginosa, and stable activity against many β-lactamases, as well as coverage of most extended-spectrum β-lactamase–producing organisms and some anaerobes. Ceftolozane–tazobactam is susceptible to hydrolysis by carbapenemase enzymes but is not affected by other resistance mechanisms such as efflux pumps and porin loss. Clinical trials demonstrated that combination treatment with ceftolozane–tazobactam plus metronidazole had efficacy comparable to that of levofloxacin in patients with complicated urinary tract infections, including pyelonephritis, and comparable to that of meropenem against complicated intraabdominal infections. A Phase III trial of ceftolozane–tazobactam versus meropenem for treatment of bacterial pneumonia, including ventilator-associated pneumonia, is underway. Adverse effects reported with ceftolozane–tazobactam use are comparable to those seen with other β-lactams (e.g., hypersensitivity, nausea, diarrhea, headache). Initially, ceftolozane–tazobactam may be reserved for targeted therapy against multidrug-resistant pathogens. Conclusion Ceftolozane–tazobactam is a new cephalosporin with enhanced activity against multidrug-resistant P. aeruginosa and other gram-negative pathogens.

Anthropogenic climate change, primarily driven by greenhouse gas emissions, is reshaping ecosystems and creating conditions that affect 58% of all known human infectious diseases, including fungal infections. Specifically, increasing temperatures, changing precipitation patterns, and extreme weather events are influencing fungal growth, distribution, and virulence. These factors may expand the geographic range of pathogenic fungi, exposing populations to novel, potentially more virulent, or drug-resistant strains. Simultaneously, human factors such as declining immunity, aging populations, and increased use of immunosuppressive therapies are enhancing host susceptibility. This review explores the intricate relationship between climate change and fungal infections, highlighting pathogens that may demonstrate increased virulence and antifungal resistance, along with emerging novel pathogens. The clinical implications are profound, with increased morbidity, mortality, and the spread of fungal infections into new regions. Immediate action is required to develop policies, educational initiatives, and novel antifungal therapies, enhance early diagnostic capabilities, and address healthcare disparities to mitigate the growing burden of fungal infections.

Background: Extended infusion (EI) dosing provides a longer time above the minimum inhibitory concentration, which is important for the clinical success of β-lactam antibiotics, especially for patients with impaired immunity. The aim of this study was to determine the feasibility and clinical impact of administering cefepime by EI as treatment of febrile neutropenia. Methods: This was a prospective, randomized, comparative pilot study. All patients received cefepime 2 g IV every 8 h, with the first dose administered using a 30-min infusion. After the first dose, patients were randomized to receive cefepime over 30 min as a standard infusion (SI) or 3 h (EI). Patients were >18 years old with febrile neutropenia (neutrophil count 38.0ºC) and received chemotherapy or stem cell transplant as treatment for malignancy. Patients were excluded for the following: allergy to a cephalosporin, creatinine clearance (CrCl) < 50 mL/min, receipt of concurrent Gram-negative antimicrobial, sepsis, or solid tumor malignancy. The primary outcome was defervescence by 72 h. Secondary outcomes included time to defervescence, clinical success, in-hospital mortality, hospital length of stay, and need for additional antimicrobials. Main results: Sixty-three patients were enrolled: 33 in the SI arm and 30 in the EI arm. The groups were similar with regard to age, gender, weight, estimated creatinine clearance, and duration of neutropenia. None of the patients in the EI arm withdrew due to practical complications of receiving EI cefepime. Twenty-three patients in the SI arm and 20 patients in the EI arm defervesced by 72 h ( p = 0.99). There were no differences in secondary outcome measures; however, patients in the EI arm appeared to have defervesced more rapidly (median 19 vs. 41 h, p = 0.305). Conclusion: Administration of cefepime by EI for the treatment of febrile neutropenia is feasible. Larger clinical trials are necessary to determine if EI cefepime imparts a clinical benefit in the treatment of febrile neutropenia.