Ceftazidime-avibactam use for the treatment of OXA-48- and/or New Delhi metallo-ß-lactamase-producing Enterobacterales in cancer patients: a retrospective observational study.

BACKGROUND: Infection is the second-leading cause of death among cancer patients, but there have been few studies on the effectiveness of novel antimicrobial agents to treat carbapenem-resistant Enterobacterales in cancer patients. OBJECTIVE: Evaluate the mortality and clinical outcomes of ceftazi-dime-avibactam for OXA-48- and/or New Delhi metallo-ß-lactamase (NDM)-producing Enterobacterales infection in cancer patients. DESIGN: Retrospective observational cohort study. SETTING: Tertiary academic medical center in Riyadh, Saudi Arabia. SUBJECTS AND METHODS: This study included patients who had cancer and received ceftazidime-avibactam for at least 72 hours for infections caused by OXA-48- and/or NDM-producing Enterobacterales. We excluded patients who died within 72 hours of treatment, patients with polymicrobial infections, and patients who did not receive appropriate antimicrobial therapy. MAIN OUTCOMES AND MEASURES: Primary outcomes were 30-day mortality and hospital mortality. Secondary outcomes included clinical cure, relapse, and reinfection. SAMPLE SIZE: 32 cancer patients. RESULTS: The 30-day mortality among all patients was 15/32 (47%), clinical cure was achieved in 19/32 (59%) of the patients, and the relapse and reinfection rates were 2/19 (10.5%) and 4/17 (23.5%), respectively. CONCLUSION: This is the largest study to evaluate clinical outcomes associated with infections caused by OXA-48- and/or NDM-producing Enterobacterales in cancer patients. The mortality rate remains high; however, ceftazidime-avibactam is an encouraging alternative for treating severe infections in cancer patients. LIMITATIONS: Small sample size and single center.

Evaluation of asymptomatic bacteruria management before and after antimicrobial stewardship program implementation: retrospective study.

BACKGROUND: The Infectious Diseases Society of America (IDSA) recommends against screening for and/or treating asymptomatic bacteriuria (ASB). This study aims to evaluate the inappropriate use of antibiotics in ASB before and after Antimicrobial Stewardship Program (ASP) implementation and advance towards its appropriate use. METHOD: We performed a retrospective study of patients diagnosed with ASB from 2016 to 2019 at a tertiary hospital in Saudi Arabia. This study included hospitalized patients ≥ 18 years old who had a positive urine culture with no documented signs or symptoms of urinary tract infection We excluded pregnant women, solid organ transplant patients, patient on active chemotherapy, and patients about to undergo urological surgery. RESULTS: A total of 716 patients with a positive urine culture were screened. Among these, we identified 109 patients with ASB who were included in our study. The rate of inappropriate antibiotic use was 95% during the study period. The implementation of the ASP Program was associated with a significant reduction in the use of carbapenems (P = 0.04) and an increase in the use of cephalosporins (P = 0.01). However, overprescribing antimicrobial agents was a concern in both eras. Approximately 90% of the microorganisms identified were gram-negative bacteria. Of those, 38.7% were multidrug-resistant strains. CONCLUSION: The urine culture order in ASB is considered relatively small number; however, it showed a high rate of the inappropriate use of antibiotics when there is an order of urine culture in both era. ASP ought to focus on targeting the ordering physician, promoting awareness and/or organizational interventions that appear to reduce the incidence of overtreatment.

Folic Acid-Terminated Poly(2-Diethyl Amino Ethyl Methacrylate) Brush-Gated Magnetic Mesoporous Nanoparticles as a Smart Drug Delivery System.

Currently, chemotherapy is an important method for the treatment of various cancers. Nevertheless, it has many limitations, such as poor tumour selectivity and multi-drug resistance. It is necessary to improve this treatment method by incorporating a targeted drug delivery system aimed to reduce side effects and drug resistance. The present work aims to develop pH-sensitive nanocarriers containing magnetic mesoporous silica nanoparticles (MMSNs) coated with pH-responsive polymers for tumour-targeted drug delivery via the folate receptor. 2-Diethyl amino ethyl methacrylate (DEAEMA) was successfully grafted on MMSNs via surface initiated ARGET atom transfer radical polymerization (ATRP), with an average particle size of 180 nm. The end groups of poly (2-(diethylamino)ethyl methacrylate) (PDEAEMA) brushes were converted to amines, followed by a covalent bond with folic acid (FA) as a targeting agent. FA conjugated to the nanoparticle surface was confirmed by X-ray photoelectron spectroscopy (XPS). pH-Responsive behavior of PDEAEMA brushes was investigated by Dynamic Light Scattering (DLS). The nanoparticles average diameters ranged from ca. 350 nm in basic media to ca. 650 in acidic solution. Multifunctional pH-sensitive magnetic mesoporous nanoparticles were loaded with an anti-cancer drug (Doxorubicin) to investigate their capacity and long-circulation time. In a cumulative release pattern, doxorubicin (DOX) release from nano-systems was ca. 20% when the particle exposed to acidic media, compared to ca. 5% in basic media. The nano-systems have excellent biocompatibility and are minimally toxic when exposed to MCF-7, and -MCF-7 ADR cells.

Glucosamine Modified the Surface of pH-Responsive Poly(2-(diethylamino)ethyl Methacrylate) Brushes Grafted on Hollow Mesoporous Silica Nanoparticles as Smart Nanocarrier.

This work presents the synthesis of pH-responsive poly(2-(diethylamino) ethyl methacrylate) (PDEAEMA) brushes anchored on hollow mesoporous silica nanoparticles (HMSN-PDEAEMA) via a surface-initiated ARGET ATRP technique. The average size of HMSNs was ca. 340 nm, with a 90 nm mesoporous silica shell. The dry thickness of grafted PDEAEMA brushes was estimated to be ca 30 nm, as estimated by SEM and TEM. The halogen group on the surface of PDEAMA brushes was successfully derivatized with glucosamine, as confirmed by XPS. The effect of pH on the size of the hybrid nanoparticles was investigated by DLS. The size of fabricated nanoparticle decreased from ca. 950 nm in acidic media to ca. 500 nm in basic media due to the deprotonation of tertiary amine in the PDEAEMA. The PDEAEMA modified HMSNs nanocarrier was efficiently loaded with doxorubicin (DOX) with a loading capacity of ca. 64%. DOX was released in a relatively controlled pH-triggered manner from hybrid nanoparticles. The cytotoxicity studies demonstrated that DOX@HMSN-PDEAEMA-Glucosamine showed a strong ability to kill breast cancer cells (MCF-7 and MCF-7/ADR) at low drug concentrations, in comparison to free DOX.

Preterm Labor Caused by Hemolysis, Elevated Liver Enzymes, Low Platelet Count (HELLP) Syndrome and Postpartum Infection Complicated with Actinomyces Species: A Case Report.

BACKGROUND Actinomyces species are normal flora of the upper respiratory, female genital, and gastrointestinal tract. Actinomyces species are generally considered to have a low virulence potential. Here we report one case of Actinomyces viscosus isolated from a neonatal blood culture as a consequence of extreme prematurity in the presence of HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome. CASE REPORT A 23-week gestational age female infant was born to a 32-year-old mother. The pregnancy was complicated by severe HELLP syndrome leading to cesarean section at 23-week gestation. The initial blood culture grew anaerobic gram-positive branching rods consistent with Actinomyces species. Due to patient instability, antibiotic was started and continued for a total of 13 days. On day of life 26, the reference laboratory identified the organism as A. viscosus by 16S ribosomal RNA. CONCLUSIONS In this case, Actinomyces species was a consequence of HELLP syndrome and consecutive extreme prematurity. Further research to look more closely at Actinomyces species isolated from neonatal blood culture will help to elucidate the true significance of these isolates.