Article
Infectious Diseases
Mustafa Sadek, Remi Le Guern, Eric Kipnis, Philippe Gosset, Laurent Poirel, Rodrigue Dessein, Patrice Nordmann
Summary: This study reports the development of cefiderocol resistance among sequential Pseudomonas aeruginosa clinical isolates, without exposure to the drug. The resistance was driven by multifactorial mechanisms, including mutational changes in iron transporter proteins associated with drug uptake and overexpression of certain genes.
EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES
(2023)
Article
Infectious Diseases
Michela Padovani, Anna Bertelli, Silvia Corbellini, Giorgio Piccinelli, Francesca Gurrieri, Maria Antonia De Francesco
Summary: This study evaluated the activity of the antimicrobial agent Cefiderocol against a range of pathogens and analyzed the resistance mechanism in two resistant Klebsiella pneumoniae isolates. The results demonstrated good effectiveness of Cefiderocol against most pathogens, but with a higher resistance rate observed. Active surveillance is necessary to control the spread of these pathogens and prevent the emergence of resistance to new drugs.
Article
Microbiology
Rio Nakamura, Merime Oota, Shuhei Matsumoto, Takafumi Sato, Yoshinori Yamano
Summary: Cefiderocol is a novel antibiotic that shows potent activity against difficult-to-treat Gram-negative bacteria, including strains resistant to carbapenems. In in vitro and animal studies, Cefiderocol demonstrated strong antimicrobial activity against Stenotrophomonas maltophilia, even against strains resistant to trimethoprim-sulfamethoxazole. These results suggest that Cefiderocol could be a promising treatment option for infections caused by S. maltophilia, especially those resistant to traditional antibiotics.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Christi L. McElheny, Erin L. Fowler, Alina Iovleva, Ryan K. Shields, Yohei Doi
Summary: The study discovered that a mutant strain of NDM-producing Klebsiella pneumoniae with high-level cefiderocol resistance can be selected under exposure to cefiderocol, but it comes with a high fitness cost. This finding is crucial for informing the stewardship of this agent in clinical settings.
MICROBIOLOGY SPECTRUM
(2021)
Article
Microbiology
Gao-Fei Du, Yu Dong, Xiaolu Fan, Ankang Yin, Yao-Jin Le, Xiao-Yan Yang
Summary: This study investigated the antibacterial mechanism of cefiderocol and found that it induces reactive oxygen species stress by increasing the levels of NADH and iron ions in Escherichia coli, leading to its antibacterial effects. The findings provide insight into the mechanisms of cefiderocol and may help in combating cefiderocol resistance in the future.
MICROBIOLOGY SPECTRUM
(2022)
Article
Biochemistry & Molecular Biology
Casin Le, Camila Pimentel, Fernando Pasteran, Marisel R. Tuttobene, Tomas Subils, Jenny Escalante, Brent Nishimura, Susana Arriaga, Aimee Carranza, Vyanka Mezcord, Alejandro J. Vila, Alejandra Corso, Luis A. Actis, Marcelo E. Tolmasky, Robert A. Bonomo, Maria Soledad Ramirez
Summary: Cefiderocol, a recently introduced antibiotic, shows reduced efficacy against A. baumannii bacteria when exposed to human fluids, potentially due to changes in gene expression. Further investigation is needed to understand the underlying mechanisms.
Review
Infectious Diseases
Stamatis Karakonstantis, Maria Rousaki, Evangelos Kritsotakis
Summary: Cefiderocol is a promising drug that can overcome most beta-lactam resistance mechanisms. Resistance is uncommon but alarming proportions have been reported in recent cohorts. Various mechanisms, especially the coexpression of multiple beta-lactamases, contribute to resistance. Heteroresistance is prevalent in Acinetobacter baumannii, but its clinical impact is still uncertain.
Review
Medicine, General & Internal
Jiahui Yao, Jin Wang, Mengli Chen, Yun Cai
Summary: Cefiderocol (CFDC) is a novel siderophore cephalosporin with unique drug delivery systems and stability to beta-lactamases, showing excellent activity against a broad range of MDR Gram-negative pathogens. However, there have been reports of drug resistance in some Gram-negative bacteria related to the expressions of specific metallo-beta-lactamases.
FRONTIERS IN MEDICINE
(2021)
Article
Infectious Diseases
Patrice Nordmann, Maxime Bouvier, Laurent Poirel, Mustafa Sadek
Summary: The Rapid Cefiderocol NP test developed in this study can rapidly and accurately identify cefiderocol resistance in MDR Enterobacterales. The test shows high sensitivity and specificity and is easy to implement in routine microbiology laboratories.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Chemistry, Multidisciplinary
Nicholas A. Bernier, James Teh, Derek Reichel, Joanne L. Zahorsky-Reeves, J. Manuel Perez, Alexander M. Spokoyny
Summary: Host-guest interactions are a growing research area where recent work has shown the ability to chemically manipulate both host and guest molecules. In this study, boron cluster derivatives were found to be encapsulated into iron oxide nanoparticles, with interactions not dependent on pH. This system was shown to be nontoxic and alter the biodistribution of guest molecules in mice.
Article
Chemistry, Analytical
Alaa Riezk, Vasin Vasikasin, Richard C. C. Wilson, Timothy M. M. Rawson, James G. G. McLeod, Rishi Dhillon, Jamie Duckers, Anthony E. G. Cass, Alison H. H. Holmes
Summary: This study aimed to establish and validate a rapid and reliable liquid chromatography-tandem mass spectrometry (LC/MS) method for the simultaneous quantification of cefiderocol and meropenem in human plasma of critically ill patients. The method involved protein precipitation using acetonitrile for sample clean-up, followed by reverse phase chromatography using triple quadrupole LC/MS. The developed method showed good linearity, accuracy, and sensitivity for both cefiderocol and meropenem, with stability at different temperatures and protein binding assessed in human plasma.
ANALYTICAL METHODS
(2023)
Article
Biology
Beibei Guo, Ying Yuan
Summary: In the era of targeted therapy, a new paradigm called DROID (Dose-Ranging Approach to Optimizing Dose) is proposed to efficiently optimize the dose of targeted oncology drugs. It leverages the well-established dose-ranging study framework used in non-oncology drugs along with established oncology dose-finding designs. DROID consists of two stages: establishing the therapeutic dose range and the recommended phase 2 dose set, and then assessing the dose-response relationship and identifying the optimal dose.
Article
Infectious Diseases
Yoshinori Yamano, Naoki Ishibashi, Miho Kuroiwa, Miki Takemura, Wang-Huei Sheng, Po-Ren Hsueh
Summary: This study conducted in Taiwan demonstrated that the addition of avibactam could significantly decrease the minimum inhibitory concentration of CFDC-non-susceptible CRAB isolates, indicating the involvement of beta-lactamases in resistance.
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
(2022)
Article
Biochemistry & Molecular Biology
Jenny Escalante, Brent Nishimura, Marisel R. R. Tuttobene, Tomas Subils, Vyanka Mezcord, Luis A. A. Actis, Marcelo E. E. Tolmasky, Robert A. A. Bonomo, Maria Soledad Ramirez
Summary: The mortality rates of patients infected with Acinetobacter baumannii who were treated with cefiderocol (CFDC) were not as favorable as those receiving the best available treatment for pulmonary and bloodstream infections. The presence of human serum albumin (HSA) in the growth medium decreases the expression of genes associated with iron uptake systems. Removing HSA from the growth medium reduces the minimal inhibitory concentration (MIC) of CFDC and enhances the expression of iron-uptake genes and decreases the expression of beta-lactamases genes.
Article
Microbiology
Mei Luo, Guozhong Chen, Chunrong Yi, Baoshuai Xue, Xiaoman Yang, Yao Ma, Zixin Qin, Jin Yan, Xiaoyun Liu, Zhi Liu
Summary: During long-term colonization in adult mice, Vibrio cholerae (V. cholerae) increased its fitness by producing nonmotile mutants through deletion of the cyclin gene dps. Methionine metabolism pathway may be involved in the increased colonization in the adult mice.
Article
Urology & Nephrology
Wasim S. El Nekidy, Albert Kadri, Terrence J. Lee-St John, Islam M. Ghazi, Derrick C. Soong
CLINICAL NEPHROLOGY
(2020)
Review
Pharmacology & Pharmacy
Wasim S. El Nekidy, Hazem Elrefaei, Terrence J. Lee St. John, Nizar M. Attallah, Farah Kablaoui, Ahmad Nusair, Bartlomiej Piechowski-Jozwiak, Janise Phillips, Islam M. Ghazi
Summary: The approved dosing of ertapenem in patients with chronic kidney disease stage 5 utilizing dialysis may lead to neurotoxicity in some cases, with risk factors including male sex, dementia, and concomitant use of certain drugs. Alternative dosing strategies may need further investigation for efficacy and safety.
ANNALS OF PHARMACOTHERAPY
(2021)
Article
Oncology
Benjamin J. Ereshefsky, Diaa Alrahmany, Wasim S. El Nekidy, Laura Pontiggia, Islam M. Ghazi
Summary: In the treatment of CDI, low-dose oral vancomycin showed equivalent outcomes compared to high-dose vancomycin, with no significant differences in secondary outcomes such as 90-day readmission/recurrence or 30-day all-cause mortality.
JOURNAL OF CHEMOTHERAPY
(2021)
Review
Microbiology
Diaa Alrahmany, Islam M. Ghazi
Summary: SARS-CoV-2 induces exaggerated host immune response, leading to mortality, requiring the search for new therapeutic approaches. Treating cytokine storm syndrome with immunomodulators and immunosuppressants could be a potential therapeutic option to reduce mortality associated with SARS-CoV-2.
REVIEWS IN MEDICAL MICROBIOLOGY
(2021)
Article
Immunology
Yi Kee Poon, Ricardo M. La Hoz, Linda S. Hynan, James Sanders, Marguerite L. Monogue
Summary: For the treatment of NTM infections in solid organ transplant recipients, there was no significant safety benefit of tedizolid over linezolid. Both tedizolid and linezolid-containing regimens showed a potential benefit in symptomatic and microbiologic improvement. Larger cohorts are needed to further clarify the comparative role of linezolid and tedizolid in the treatment of NTM infections in SOT recipients.
OPEN FORUM INFECTIOUS DISEASES
(2021)
Article
Public, Environmental & Occupational Health
Diaa Alrahmany, Benjamin J. Ereshefsky, Wasim S. El Nekidy, Gehan Harb, Laura Pontiggia, Islam M. Ghazi
Summary: This study analyzed data from 204 patients with C. difficile infection and found that factors such as female gender, older age, prior exposure to clindamycin, concurrent use of aztreonam, and longer hospital stay were associated with the occurrence of rCDI. These risk factors could help identify patients who may benefit from closer monitoring and interventions to prevent rCDI and improve clinical outcomes.
JOURNAL OF INFECTION AND PUBLIC HEALTH
(2021)
Article
Infectious Diseases
Diaa Alrahmany, Ahmed F. Omar, Gehan Harb, Wasim S. El Nekidy, Islam M. Ghazi
Summary: The study found that compared to combination therapy, monotherapy in patients with AB infections has lower mortality rates, shorter hospital stays, and fewer adverse events. Colistin monotherapy and certain Colistin combinations showed nearly equivalent mortality outcomes, while patients on combination therapy were more susceptible to adverse events.
Article
Pharmacology & Pharmacy
Wasim S. El Nekidy, Manal M. Abdelsalam, Ahmad R. Nusair, Rania El Lababidi, Ruba Z. Dajani, Terrence J. Lee St John, Islam M. Ghazi
Summary: This study found that cefoxitin demonstrated a similar microbiologic cure rate compared to ertapenem for the treatment of urinary tract infections, but was not as effective in clinical cure. The 90-day recurrence rate was significantly lower in the cefoxitin group compared to the ertapenem group. In many clinical settings, cefoxitin can be used as a carbapenem-sparing agent as an alternative to ertapenem.
Article
Infectious Diseases
Marc D. Esquivel, Marguerite L. Monogue, Greg S. Smith, James D. Finklea, James M. Sanders
Summary: This retrospective observational cohort study compared the safety and efficacy of ceftaroline with vancomycin for the treatment of methicillin-resistant Staphylococcus aureus (MRSA)-mediated acute pulmonary exacerbations (APEs) in adult cystic fibrosis (CF) patients. The study found that ceftaroline was a viable alternative treatment option for MRSA-mediated APEs in adult CF patients, with similar outcomes to vancomycin.
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
(2022)
Article
Infectious Diseases
Diaa Alrahmany, Ahmed F. Omar, Aisha Alreesi, Gehan Harb, Islam M. Ghazi
Summary: This study investigated factors contributing to mortality rates in nosocomial Acinetobacter baumannii infections, finding age, admission to critical care units, and infectious diagnosis to be significantly associated with higher mortality. Interventions such as improving multidisciplinary infection control, regular disinfection, and optimal intubation practices can reduce infection-related mortality rates.
Article
Infectious Diseases
Diaa Alrahmany, Ahmed F. Omar, Salima R. S. Al-Maqbali, Gehan Harb, Islam M. Ghazi
Summary: This study investigated infection patterns and risk factors for mortality among G6PD-deficient patients in Oman and provided recommendations for antimicrobial stewardship. The results showed a significant association between G6PD deficiency and multidrug-resistant and hospital-acquired infections, which were also associated with a high mortality rate.
Article
Urology & Nephrology
Wasim S. El Nekidy, Jihad Mallat, Ahmad R. Nusair, Ayah H. Eshbair, Nizar Attallah, Mohamad Mooty, Muriel Ghosn, Islam M. Ghazi
Summary: This study investigated the impact of different antimicrobials on clinical and microbiologic outcomes in hemodialysis (HD) dependent patients with urinary tract infection (UTI). The findings showed a high rate of clinical and microbiologic cure in both oliguric and anuric patients, with low recurrence and mortality rates. It suggests that treatment recommendations for UTI should take into account clinical and microbiologic outcomes as well as achievable urinary concentration.
HEMODIALYSIS INTERNATIONAL
(2022)
Article
Infectious Diseases
Daniel N. Maxwell, Jiwoong Kim, Christine A. Pybus, Leona White, Richard J. Medford, Laura M. Filkins, Marguerite L. Monogue, Meredith M. Rae, Dhara Desai, Andrew E. Clark, Xiaowei Zhan, David E. Greenberg
Summary: Polyclonal heteroresistance (PHR) is common among Pseudomonas aeruginosa in the cystic fibrosis lung, and traditional microbiological methods often fail to detect resistant subpopulations. However, whole-genome sequencing and a machine-learning association model can successfully identify resistance variants in this context.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Diaa Alrahmany, Ahmed F. Omar, Wael Hafez, Sara Albaloshi, Gehan Harb, Islam M. Ghazi
Summary: Disturbances in blood cell count or maturity weaken microbial defense capacity, increasing susceptibility to infections. Glucose-6-phosphate deficient patients with compromised cell integrity are at higher risk of infections and mortality. This study aimed to investigate the risk factors for infection mortality in this patient population.
Article
Infectious Diseases
Marguerite L. Monogue, James M. Sanders, Christine A. Pybus, Jiwoong Kim, Xiaowei Zhan, Andrew E. Clark, David E. Greenberg
Summary: This study found polyclonal and monoclonal heteroresistance (HR) to ceftolozane/tazobactam in Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients, with approximately one-fourth of the samples showing discrepancies in ceftolozane/tazobactam susceptibility between laboratory results and clinical reports. No known resistance genes were found in the HR isolates, suggesting the limitations of traditional susceptibility testing methods in CF specimens.
JAC-ANTIMICROBIAL RESISTANCE
(2023)
Review
Infectious Diseases
Allison M. Hitchcock, Wesley D. Kufel, Keri A. Mastro Dwyer, Eric F. Sidman
Summary: Lenacapavir is a novel HIV-1 treatment option for patients with multidrug-resistant (MDR) HIV-1 infection. It has a favorable pharmacokinetic profile and has shown good tolerability and efficacy in clinical trials.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2024)
Article
Infectious Diseases
Roberta Gagliardini, Alessandro Tavelli, Stefano Rusconi, Sergio Lo Caputo, Vincenzo Spagnuolo, Maria Mercedes Santoro, Andrea Costantini, Alessandra Vergori, Franco Maggiolo, Andrea Giacomelli, Giulia Burastero, Giordano Madeddu, Eugenia Quiros Roldan, Antonella d'Arminio Monforte, Andrea Antinori, Alessandro Cozzi-Lepri
Summary: This study evaluated multiple treatment failures to modern antiretroviral therapy in HIV-infected individuals and found that approximately 4% of them were difficult to treat. The difficult to treat group, compared to the non-difficult to treat group, was characterized by older age, higher prevalence of AIDS, lower CD4+ cell count, and higher risk of treatment failure.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2024)