Global trends in carbapenem- and difficult-to-treat-resistance among World Health Organization priority bacterial pathogens: ATLAS surveillance program 2018-2022.

OBJECTIVES: To report trends in carbapenem resistance and difficult-to-treat resistance (DTR) among clinical isolates of Gram-negative priority pathogens collected by the ATLAS global surveillance program from 2018 to 2022. METHODS: Reference broth microdilution testing was performed in a central laboratory for 79,214 Enterobacterales, 30,504 Pseudomonas aeruginosa, and 13,500 Acinetobacter baumannii-calcoaceticus complex isolates collected by a constant set of 157 medical centres in 49 countries in Asia Pacific (APAC), Europe (EUR), Latin America (LATAM), Middle East-Africa (MEA), and North America (NA) regions. MICs were interpreted by 2023 CLSI M100 breakpoints. ß-lactamase genes were identified for meropenem-nonsusceptible (MIC ≥2 mg/L) Enterobacterales isolates. RESULTS: Carbapenem-resistant Enterobacterales (CRE) detection increased (P < 0.05) in APAC, EUR, LATAM, and MEA regions and decreased in NA, while annual DTR percentages increased in all five regions. Carbapenem-resistant P. aeruginosa (CRPA; decreased in MEA region) and carbapenem-resistant A. baumannii-calcoaceticus complex (CRAB; decreased in MEA region and increased in EUR) remained relatively stable over time in all regions, although notably, annual percentages of CRAB and DTR A. baumannii-calcoaceticus complex isolates were consistently >25 percentage points lower in NA than in other regions. For all regions except NA, the majority of changes in CRE percentages could be attributed to hospital-acquired infections. Among meropenem-nonsusceptible Enterobacterales, KPC was the most frequent carbapenemase in NA and EUR each year. NDM was the most prevalent carbapenemase detected in 2022 in other global regions. CONCLUSION: CRE, CRPA, CRAB, and DTR rates vary among global regions over time highlighting the need for continuing surveillance to inform treatment strategies and antimicrobial stewardship.

In vitro activity of ceftaroline against bacterial isolates causing skin and soft tissue and respiratory tract infections collected in Latin American countries, ATLAS program 2016-2020.

OBJECTIVES: Ceftaroline, a broad-spectrum cephalosporin, has activity against Gram-positive and several Gram-negative bacteria (GNB). This study aimed to evaluate the antimicrobial activity of ceftaroline and comparators against isolates causing skin and soft tissue infections (SSTIs) and respiratory tract infections (RTIs) collected in Latin America (LATAM) in 2016-2020 as part of the Antimicrobial Testing Leadership and Surveillance program (ATLAS). METHODS: Minimum inhibitory concentrations were determined using both Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. RESULTS: Ceftaroline demonstrated potent activity against methicillin-susceptible Staphylococcus aureus (CLSI/EUCAST: MIC90 0.25 mg/L; susceptibility 100%), whereas activity against methicillin-resistant S. aureus varied for SSTIs (MIC90 1 mg/L; susceptibility 92.5%) and RTIs isolates (MIC90 2 mg/L; susceptibility 72.9%) isolates. For Streptococcus pneumoniae, particularly penicillin-resistant isolates commonly causing respiratory infections, high ceftaroline activity (MIC90 0.25 mg/L; susceptibility 100%/98.4%) was noted. All isolates of ß-hemolytic streptococci were susceptible to ceftaroline (S. agalactiae: MIC90 0.03 mg/L [SSTIs]; MIC90 0.015 mg/L (RTIs); susceptibility 100%; S. pyogenes: MIC90 0.008 mg/L; susceptibility 100%). Ceftaroline was highly active against Haemophilus influenzae, including ß-lactamase positive isolates (MIC90 0.06 mg/L; susceptibility 100%/85.7%). Ceftaroline demonstrated high activity against non-ESBL-producing GNB (E. coli: MIC90 0.5 mg/L, susceptibility 91.9%; K. pneumoniae: MIC90 0.25 mg/L, susceptibility 95.1%; K. oxytoca, MIC90 0.5 mg/L; susceptibility 95.7%). CONCLUSION: Ceftaroline was active against the recent collection of bacterial pathogens commonly causing SSTIs and RTIs in LATAM. Local and regional surveillance of antimicrobial resistance patterns are crucial to understand evolving resistance and guide treatment management.

In vitro activity of aztreonam-avibactam against Enterobacterales isolates collected in Latin America, Africa/Middle East, Asia, and Eurasia for the ATLAS Global Surveillance Program in 2019-2021.

This study aimed to report reference method antimicrobial susceptibility results for 24,937 recent (2019-2021) clinical isolates of Enterobacterales from 27 countries in Latin America, Eurasia, Africa/Middle East, and Asia with a focus on the investigational combination aztreonam-avibactam against metallo-ß-lactamase (MBL) isolates. Antimicrobial susceptibility testing was performed by the CLSI broth microdilution methodology. Minimum inhibitory concentrations (MICs) were interpreted using the CLSI (2022) breakpoints for all agents except aztreonam-avibactam (provisional pharmacokinetic/pharmacodynamic susceptible breakpoint, ≤ 8 mg/L) and tigecycline (US-FDA). Molecular testing for ß-lactamase genes was performed on isolates with meropenem MICs ≥ 2 mg/L, ceftazidime-avibactam MICs ≥ 16 mg/L, and/or aztreonam-avibactam MICs ≥ 16 mg/L, and 50% of isolates of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Klebsiella variicola, and Proteus mirabilis testing with ceftazidime and/or aztreonam MICs ≥ 2 mg/L. Aztreonam-avibactam inhibited 99.8% of all Enterobacterales at ≤ 8 mg/L (MIC90, 0.25 mg/L) and maintained activity against phenotypically resistant subsets of multidrug-resistant (MDR) (99.5% susceptible), extensively drug-resistant (XDR) (98.7%), and carbapenem-resistant Enterobacterales (CRE) (99.1%) isolates. At ≤ 8 mg/L, aztreonam-avibactam inhibited 100%, 99.6%, 99.6%, and 98.8% of KPC-, OXA-48-like-, ESBL-, and MBL-carrying isolates, respectively. MBL-positive isolates were most prevalent in India (20.5%), Guatemala (13.8%), and Jordan (13.2%). No differences in the activity of aztreonam-avibactam were observed across the global regions evaluated. At a concentration of ≤ 8 mg/L, aztreonam-avibactam inhibited almost all Enterobacterales collected from developing countries, including MBL-producing isolates. The widespread dissemination of MBLs among Enterobacterales highlights the unmet need for new agents such as aztreonam-avibactam for the treatment of CRE infections.

Antimicrobial Susceptibility Among Gram-Negative Isolates in Pediatric Patients in Latin America, Africa-Middle East, and Asia From 2016-2020 Compared to 2011-2015: Results From the ATLAS Surveillance Study.

BACKGROUND: Antimicrobial resistance (AMR) data in the pediatric population are limited, particularly in developing countries. This study assessed the AMR profile and key resistance phenotypes and genotypes for Gram-negative bacteria (GNB) isolates collected as part of the Antimicrobial Testing Leadership and Surveillance program from pediatric patients in Latin America, Africa-Middle East, and Asia in 2016-2020 versus 2011-2015. METHODS: Minimum inhibitory concentrations by broth microdilution methodology were interpreted per the Clinical and Laboratory Standards Institute. European Committee on Antimicrobial Susceptibility Testing breakpoints were used for interpreting colistin activity. ß-lactamase genes were screened by polymerase chain reaction and sequencing. RESULTS: For Acinetobacter baumannii, low susceptibility (<60.0%) was observed for all antimicrobials, except colistin (≥92.9%), across regions and year periods. Ceftazidime-avibactam, amikacin, colistin, and meropenem were mostly active (78.6%-100.0%) against Enterobacter cloacae, Escherichia coli, and Klebsiella pneumoniae. For Pseudomonas aeruginosa, susceptibility to ceftazidime-avibactam, amikacin, and colistin was ≥85.9%. Among resistance phenotypes, carbapenem-resistant (CR, ≥44.8%) and difficult-to-treat resistant (DTR, ≥37.1%) rates were the highest in A. baumannii. A consistent increase in CR and DTR K. pneumoniae was noted across regions over time. Extended-spectrum ß-lactamases (ESBL)-producing K. pneumoniae (32.6%-55.6%) were more frequent than ESBL-producing E. coli (25.3%-37.1%). CTX-M was the dominant ESBL among Enterobacterales. NDM-positive Enterobacterales species and VIM-positive P. aeruginosa were identified across regions. CONCLUSIONS: This study identified high susceptibility to few agents for key GNB in pediatric patients. Continued surveillance of resistance phenotypes and genotypes at regional levels may help to guide appropriate treatment decisions.

Pericapsular nerve group block in hip arthroplasty: A prospective randomized trial.

OBJECTIVES: This study aimed to evaluate the analgesic effect of the ultrasound-guided pericapsular nerve group (PENG) block in hip arthroplasty (HA) surgery. DESIGN: A prospective double-blinded, randomized study. SETTING: Tertiary institutional clinical care. PARTICIPANTS: Fifty patients, more than 50 years old of both genders, were chosen according to the American Society of Anesthesiologists classification, with physical status I-III, and scheduled for unilateral HA surgeries. INTERVENTIONS: Patients were randomized to receive either a sham PENG block with 20 mL of normal saline (control group) or a PENG block with 20 mL of bupivacaine 0.25 percent (PENG group). MAIN OUTCOME MEASURES: From the onset of the first request for rescue opioid analgesia, preoperative pain scores before and after block (at rest and with a raised straight leg), the incidence of quadriceps weakness after the block, intraoperative fentanyl consumption, post-operative pain scores, and morphine consumption, besides the presence and frequency of adverse events, were recorded. RESULTS: The patients undergoing PENG block with bupivacaine had prolonged durations before the first analgesic request, lower perioperative pain scores, less intraoperative rescue fentanyl, and less post-operative morphine consumption than the control group, with nonsignificant motor weakness after the block and similar adverse events. CONCLUSIONS: The PENG block provided effective perioperative analgesia for HA with prolonged duration of analgesia, nonsignificant motor effects, reduced perioperative opioids consumption, and no major side effects.

A Narrative Review of Healthcare-Associated Gram-Negative Infections Among Pediatric Patients in Middle Eastern Countries.

INTRODUCTION: Gram-negative bacteria (GNB) have become prominent across healthcare and community settings due to factors including lack of effective infection control and prevention (ICP) and antimicrobial stewardship programs (ASPs), GNB developing antimicrobial resistance (AMR), and difficulty treating infections. This review summarizes available literature on healthcare-associated infections (HAIs) in Middle Eastern pediatric patients. METHODS: Literature searches were performed with PubMed and Embase databases. Articles not reporting data on GNB, HAIs, pediatric patients, and countries of interest were excluded. RESULTS: The searches resulted in 220 publications, of which 49 met the inclusion criteria and 1 additional study was identified manually. Among 19 studies across Egypt reporting GNB prevalence among pediatric patients, Klebsiella species/K. pneumoniae and Escherichia coli were typically the most common GNB infections; among studies reporting carbapenem resistance and multidrug resistance (MDR), rates reached 86% and 100%, respectively. Similarly, in Saudi Arabia, Klebsiella spp./K. pneumoniae and E. coli were the GNB most consistently associated with infections, and carbapenem resistance (up to 100%) and MDR (up to 75%) were frequently observed. In other Gulf Cooperation Council countries, including Kuwait, Oman, and Qatar, carbapenem resistance and MDR were also commonly reported. In Jordan and Lebanon, E. coli and Klebsiella spp./K. pneumoniae were the most common GNB isolates, and AMR rates reached 100%. DISCUSSION: This review indicated the prevalence of GNB-causing HAIs among pediatric patients in Middle Eastern countries, with studies varying in reporting GNB and AMR. Most publications reported antimicrobial susceptibility of isolated GNB strains, with high prevalence of extended-spectrum beta-lactamase-producing K. pneumoniae and E. coli isolates. A review of ASPs highlighted the lack of data available in the region. CONCLUSIONS: Enhanced implementation of ICP, ASPs, and AMR surveillance is necessary to better understand the widespread burden of antimicrobial-resistant GNB and to better manage GNB-associated HAIs across Middle Eastern countries.

The role of diagnostic tests in antifungal stewardship for treating invasive fungal infections: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of an article originally published in the journal Open Forum Infectious Diseases. Invasive fungal infections are caused by fungi. They can spread to deeper parts of the body. Some diagnostic tests are slow and may delay treatment. Better tests help to identify infection early in patients. An antifungal stewardship (shortened to AFS) program is a stepwise process to improve how patients are treated. AFS programs using diagnostic tests may help to manage infections. In this study, researchers wanted to know the impact of such AFS programs. To do so, they looked at the information from 17 previously published studies, which is summarized here. WHAT WERE THE RESULTS?: Infections were identified and treated faster in studies with improved diagnostic tests. Treatment cost decreased when infections were identified and treated early. Patients were treated for shorter periods of time. They also spent less time in hospital. Number of deaths were less. WHAT DO THE RESULTS OF THE STUDY MEAN?: AFS programs based on diagnostic tests helped patients.

The Role of Diagnostics-Driven Antifungal Stewardship in the Management of Invasive Fungal Infections: A Systematic Literature Review.

Antifungal stewardship (AFS) programs are key to optimizing antifungal use and improving outcomes in patients with invasive fungal infections. Our systematic literature review evaluated the impact of diagnostics in AFS programs by assessing performance and clinical measures. Most eligible studies were from Europe and the United States (n = 12/17). Diagnostic approaches included serum ß-1-3-D-glucan test (n/N studies, 7/17), galactomannan test (4/17), computed tomography scan (3/17), magnetic resonance (2/17), matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS; 2/17), polymerase chain reaction (1/17), peptide nucleic acid fluorescent in situ hybridization (PNA-FISH) assay (1/17), and other routine methods (9/17). Time to species identification decreased significantly using MALDI-TOF and PNA-FISH (n = 2). Time to targeted therapy and length of empiric therapy also decreased (n = 3). Antifungal consumption decreased by 11.6%-59.0% (7/13). Cost-savings ranged from 13.5% to 50.6% (5/10). Mortality rate (13/16) and length of stay (6/7) also decreased. No negative impact was reported on patient outcomes. Diagnostics-driven interventions can potentially improve AFS measures (antifungal consumption, cost, mortality, and length of stay); therefore, AFS implementation should be encouraged.

Carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa causing infection in Africa and the Middle East: a surveillance study from the ATLAS programme (2018-20).

Objectives: To determine the in vitro susceptibility of Enterobacterales (n = 5457) and Pseudomonas aeruginosa (n = 1949) isolated from hospitalized patients in Africa (three countries) and the Middle East (five countries) in 2018-20 to a panel of 11 antimicrobials and to identify ß-lactamase/carbapenemase genes in isolates with meropenem-non-susceptible and/or ceftazidime/avibactam-resistant phenotypes. Methods: CLSI broth microdilution testing generated MICs that were interpreted using CLSI (2021) breakpoints. ß-Lactamase/carbapenemase genes were identified using multiplex PCR assays. Results: Enterobacterales isolates were highly susceptible to amikacin (96.7%), ceftazidime/avibactam (96.6%) and tigecycline (96.0%), and slightly less susceptible to meropenem (94.3%). In total, 337 Enterobacterales isolates (6.2% of all Enterobacterales isolates) carried one or more carbapenemase genes: 188 isolates carried a serine carbapenemase (178 OXA, 10 KPC) and 167 isolates carried an MBL (18 isolates carried both an MBL and an OXA). NDM-1 was the most common MBL identified (64.1% of NDM enzymes; 59.9% of all MBLs). OXA-48 (47.8%) and OXA-181 (38.8%) were the most common OXAs detected. P. aeruginosa isolates were most susceptible to ceftazidime/avibactam (89.1%) and amikacin (88.9%). Only 73.1% of P. aeruginosa isolates were meropenem susceptible. The majority (68.1%) of P. aeruginosa isolates tested for carbapenemase/ß-lactamase genes were negative. In total, 88 isolates (4.5% of all P. aeruginosa isolates) carried one or more carbapenemase genes: 81 isolates carried an MBL and 8 carried a GES carbapenemase (1 isolate carried genes for both). Conclusions: Carbapenemase detection was closely associated with meropenem-non-susceptible phenotypes for Enterobacterales (89.1%) but not for P. aeruginosa (24.2%). Wide geographic variation in carbapenemase type and frequency of detection was observed.

Antimicrobial susceptibility testing of clinical isolates of Gram-negative bacilli collected in Morocco by the ATLAS Global Surveillance Program from 2018 to 2020.

OBJECTIVES: To report reference method antimicrobial susceptibility testing results for recent clinical isolates of Gram-negative bacilli from Morocco. METHODS: CLSI (Clinical and Laboratory Standards Institute) broth microdilution antimicrobial susceptibility testing was performed by a central laboratory for isolates of Enterobacterales (n = 810), Pseudomonas aeruginosa (n = 321), and Acinetobacter baumannii (n = 191) collected in 2018-2020 by three hospital laboratories in Morocco. MICs were interpreted using both CLSI (2021) and EUCAST (European Committee on Antimicrobial Susceptibility Testing) (2021) breakpoints. Molecular testing for ß-lactamase genes was performed on isolates meeting defined screening criteria. RESULTS: Most isolates of Enterobacterales were susceptible (CLSI/EUCAST breakpoints) to amikacin (98.0%/96.2%), ceftazidime-avibactam (94.8%/94.8%), and meropenem (92.5%/94.2%). Of Enterobacterales isolates eligible for ß-lactamase gene screening (n = 210), 174 were ESBL-positive, 40 were metallo-ß-lactamase-positive (all NDM), 39 were serine carbapenemase-positive (all OXA); and 7 isolates carried both OXA-48 and NDM-1. Amikacin (89.1%/89.1%) and ceftazidime-avibactam (88.2%/88.2%) were the most active agents tested against P. aeruginosa. Applying CLSI and EUCAST breakpoints, MDR rates were 21.9% and 29.3% for Enterobacterales and 18.4% and 21.8% for P. aeruginosa. Susceptible rates for amikacin, ceftazidime-avibactam, and meropenem were 93.2%/89.5%, 77.4%/82.3%, and 67.8%/80.2% for MDR Enterobacterales and 50.8%/57.1%, 40.7%/45.7%, and 27.1/32.9% for MDR P. aeruginosa. ≥70% of A. baumannii isolates were resistant to all agents tested (except colistin, EUCAST breakpoints only) including amikacin and meropenem. CONCLUSION: Newer ß-lactam/ß-lactamase inhibitor combinations such as ceftazidime-avibactam warrant testing and reporting for Enterobacterales and P. aeruginosa in Morocco given the presence of significant resistance to first-line ß-lactams and fluoroquinolones, pervasive ESBLs and carbapenemases, and toxicity concerns associated with some second-line agents.

Efficacy and Safety of Ceftaroline Fosamil in Hospitalized Patients with Community-Acquired Pneumonia in China: Subset Analysis of an International Phase 3 Randomized Controlled Trial.

BACKGROUND: Ceftaroline fosamil has demonstrated superior clinical efficacy versus ceftriaxone for hospitalized adults with moderate-to-severe community-acquired pneumonia (CAP) in a Phase 3 trial in Asia and in a meta-analysis of three trials in Asia, North America, and Europe. Efficacy and safety outcomes for the subset of patients in China in the ASIA CAP trial were analyzed to determine if the same conclusions hold in the China subpopulation. METHODS: Hospitalized adults with Pneumonia Outcomes Research Team risk class III-IV CAP were randomized (1:1) to receive either intravenous ceftaroline fosamil 600 mg every 12 h or ceftriaxone 2 g every 24 h for 5-7 days. The primary efficacy variable was clinical response at test-of-cure (TOC) in the clinically evaluable (CE) population. Secondary endpoints included microbiological responses and safety. RESULTS: Of 302 patients randomized in China, 205 were included in the CE population. Clinical cure rates at TOC were 80/105 (76.2%) for ceftaroline fosamil and 61/100 (61.0%) for ceftriaxone (difference 15.2%, 95% CI 2.5, 27.6), thereby meeting predefined non-inferiority and superiority criteria for the overall study. Subgroup analyses of the primary endpoint demonstrated consistency of favourable efficacy of ceftaroline fosamil across age groups, Pneumonia Outcomes Research Team risk classes and CURB-65 scores. Microbiological responses were presumed from clinical outcomes. Adverse events were consistent with the study treatments' known safety profiles. CONCLUSION: The China subset results are consistent with the overall study population, despite the smaller sample size. Ceftaroline fosamil was both non-inferior and superior to ceftriaxone for empiric treatment of Chinese patients with moderate-to-severe CAP. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01371838.

In vitro activity of ceftazidime/avibactam against clinical isolates of Enterobacterales and Pseudomonas aeruginosa from Middle Eastern and African countries: ATLAS global surveillance programme 2015-18.

OBJECTIVES: To assess the in vitro activity of ceftazidime/avibactam against a recent, 2015-18, collection of clinical isolates of Gram-negative bacilli from Middle Eastern and African countries with a focus on isolates from ICUs and with MDR and difficult-to-treat resistance (DTR) phenotypes. METHODS: Antimicrobial susceptibility testing of 4608 isolates of Enterobacterales (997 isolates from ICU patients) and 1358 isolates of Pseudomonas aeruginosa (374 isolates from ICU patients) was performed by CLSI broth microdilution methodology in a central laboratory. MICs were interpreted using both CLSI (2020) and EUCAST (2020) MIC breakpoints. RESULTS: Most isolates of Enterobacterales (Middle East: ICU, 99.1% susceptible, non-ICU, 99.1%; Africa: ICU, 96.9% susceptible, non-ICU, 98.3%) and P. aeruginosa (Middle East: ICU, 93.4%, non-ICU, 92.1%; Africa: ICU, 89.8%; non-ICU, 94.1%) were susceptible to ceftazidime/avibactam. Applying CLSI and EUCAST breakpoints, MDR rates were similar for Enterobacterales (27.8%-36.0% of isolates) and P. aeruginosa (25.0%-36.4%) while DTR rates were lower for Enterobacterales (1.6%-1.8%) than for P. aeruginosa (5.2%-7.4%). Percentage susceptible rates for ceftazidime/avibactam for MDR Enterobacterales were 96.8%-97.5% (Middle East) and 92.5%-94.3% (Africa) while rates for P. aeruginosa were 70.1%-80.0% (Middle East) and 69.5%-78.2% (Africa). 60.5%-65.8% (Middle East) and 38.9%-52.2% (Africa) of isolates of Enterobacterales with DTR phenotypes were ceftazidime/avibactam susceptible as were 29.2%-31.1% (Middle East) and 28.2%-35.8% (Africa) of DTR P. aeruginosa. CONCLUSIONS: Overall, the isolates of Enterobacterales and P. aeruginosa tested from Middle Eastern and African countries were highly susceptible to ceftazidime/avibactam. Most MDR and many DTR isolates of Enterobacterales and P. aeruginosa were susceptible to ceftazidime/avibactam.

Evaluation of the in vitro activity of ceftaroline, ceftazidime/avibactam and comparator antimicrobial agents against clinical isolates from paediatric patients in Kuwait: ATLAS data 2012-19.

Objectives: To report antimicrobial resistance data for Gram-positive and Gram-negative pathogens isolated from paediatric patients in three hospitals in Kuwait during 2012-19. Methods: In vitro activity of antimicrobials against isolates from documented infections was determined using CLSI broth microdilution method and breakpoints at a central laboratory. Enterobacterales and Pseudomonas aeruginosa isolates were screened for ß-lactamases using multiplex PCR assays. Phenotypic determination of resistance in Haemophilus influenzae and Gram-positive isolates was performed using standard methodologies. Results: Among 515 Enterobacterales isolates, 29.3% were ESBL-positive; susceptibility was highest to amikacin, ceftazidime/avibactam and meropenem (≥97.4%), regardless of ESBL status. CTX-M-15 was identified in 87.1% of ESBL-positive Escherichia coli and 84.2% of ESBL-positive Klebsiella pneumoniae isolates. Of 111 P. aeruginosa isolates, 9.9% were MDR and 12.6% meropenem-resistant (MEM-R). Amikacin and ceftazidime/avibactam had the highest susceptibility rates in the overall group (≥92.8%), with reduced rates among MDR and MEM-R isolates. All 269 MRSA and 180 MSSA isolates were susceptible to daptomycin, linezolid, teicoplanin, tigecycline and vancomycin. All MSSA and 99.3% of MRSA were ceftaroline susceptible. All 168 pneumococcal isolates were susceptible to ceftaroline, linezolid, tigecycline and vancomycin. H. influenzae and Streptococcus pyogenes ceftaroline susceptibility rates were ≥93.3% and ≥95.6%. Conclusions: Most isolates of Enterobacterales (including resistant phenotypes) and P. aeruginosa from Kuwait during 2012-19 were susceptible to ceftazidime/avibactam. Ceftaroline was active against most Gram-positive isolates, including resistant phenotypes, and ESBL-negative Enterobacterales. These results indicate that novel antibiotics such as ceftazidime/avibactam and ceftaroline represent valuable treatment options for paediatric infections, including those caused by MDR organisms.

In vitro activity of ceftaroline against bacterial pathogens isolated from patients with skin and soft tissue and respiratory tract infections in the Middle East and Africa: AWARE global surveillance programme 2015-2018.

OBJECTIVES: To report antimicrobial susceptibility testing surveillance data for ceftaroline and comparative agents from the AWARE global surveillance programme for bacterial pathogens causing skin and soft tissue infections (SSTIs) and lower respiratory infections (RTIs) in Middle East and African countries from 2015 to 2018. METHODS: Pathogens were identified by MALDI-TOF/MS. Antimicrobial susceptibility testing was performed using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. MICs were interpreted by both CLSI (M100, 2020) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) (v 10.0, 2020) breakpoints. RESULTS: All MSSA (n = 1125) and 93.9% of MRSA (n = 1235) were susceptible to ceftaroline (MIC ≤ 1 µg/mL, CLSI and EUCAST). The maximum ceftaroline MIC observed for MRSA was 2 µg/mL; no ceftaroline-resistant MRSA were identified among SSTI (CLSI and EUCAST) and RTI (CLSI) isolates. All isolates of ß-haemolytic Streptococcus (n = 324), and penicillin-susceptible (PSSP) and -intermediate Streptococcus pneumoniae (PISP; n = 369) were susceptible to ceftaroline. Rates of susceptibility to ceftaroline for penicillin-resistant S. pneumoniae (penicillin MIC ≥ 2 µg/mL; n = 175), and ß-lactamase-negative (BLNHI; n = 224) and ß-lactamase-positive Haemophilus influenzae (n = 49) were 99.4%, 98.7%, and 98.0% (CLSI) and 92.6%, 98.2%, and 83.7% (EUCAST), respectively. Rates of susceptibility to ceftaroline for ESBL-negative Escherichia coli (n = 442), Klebsiella pneumoniae (n = 381), and Klebsiella oxytoca (n = 103) were 92.1%, 93.2%, and 96.1%, respectively. CONCLUSION: Ceftaroline-resistant isolates of MRSA causing SSTIs were not identified in Middle East and African countries in 2015-2018 using recently revised CLSI (in 2019) or EUCAST (in 2018) breakpoint criteria. Common bacterial pathogens causing SSTIs (Staphylococcus aureus, ß-haemolytic Streptococcus) and lower RTIs (PSSP, PISP, BLNHI) demonstrated no resistance or low levels of resistance (0-1.8%) to ceftaroline.

Orthopaedic Surgery Elicits a Systemic Anti-Inflammatory Signature.

Little information is available on the functional activity of leukocytes after arthroplasty or the expansion of populations with immune suppressive properties during the acute post-operative period. Synovial fluid and matched pre- and post-surgical blood samples were collected from total hip and knee arthroplasty patients (THA and TKA, respectively) to examine the impact of surgery on peripheral blood leukocyte frequency, bactericidal activity, and inflammatory mediator expression. For spinal surgeries, inflammatory mediator production by peripheral blood mononuclear cells (PBMCs) pre- and post-surgery was examined. An expansion of immune suppressive granulocytic myeloid-derived suppressor cells (G-MDSCs) was observed following arthroplasty, which correlated with significantly increased serum interleukin-10 (IL-10) levels. Analysis of synovial fluid from THA and TKAs revealed reduced granulocyte colony-stimulating factor (G-CSF) and soluble CD40 ligand (sCD40L) and increased interleukin-6 (IL-6), monocyte chemoattractant protein 2 (CCL2) and Fms-like tyrosine kinase 3 ligand (Flt-3L) compared to pre- and post-surgical serum. For the spinal surgery cohort, stimulation of PBMCs isolated post-surgery with bacterial antigens produced significantly less pro-inflammatory (IL-1α, IL-1ß, interleukin-1 receptor antagonist (IL-1RA), IL-12p40, growth-related oncogene-α/GRO-α (CXCL1) and 6Ckine (CCL21)) and more anti-inflammatory/tissue repair mediators (IL-10, G-CSF and granulocyte-macrophage colony-stimulating factor (GM-CSF)) compared to PBMCs recovered before surgery. The observed bias towards systemic anti-inflammatory changes without concomitant increases in pro-inflammatory responses may influence susceptibility to infection following orthopaedic surgery in the context of underlying co-morbidities or risk factors.

New Rare Ent-Clerodane Diterpene Peroxides from Egyptian Mountain Tea (Qourtom) and Its Chemosystem as Herbal Remedies and Phytonutrients Agents.

Genus Stachys, the largest genera of the family Lamiaceae, and its species are frequently used as herbal teas due to their essential oils. Tubers of some Stachys species are also consumed as important nutrients for humans and animals due to their carbohydrate contents. Three new neo-clerodane diterpene peroxides, named stachaegyptin F-H (1, 2, and 4), together with two known compounds, stachysperoxide (3) and stachaegyptin A (5), were isolated from Stachys aegyptiaca aerial parts. Their structures were determined using a combination of spectroscopic techniques, including HR-FAB-MS and extensive 1D and 2D NMR (1H, 13C NMR, DEPT, 1H-1H COSY, HMQC, HMBC and NOESY) analyses. Additionally, a biosynthetic pathway for the isolated compounds (1-5) was discussed. The chemotaxonomic significance of the isolated diterpenoids of S. aegyptiaca in comparison to the previous reported ones from other Stachys species was also studied.

Molecular epidemiology and expression of capsular polysaccharides in Staphylococcus aureus clinical isolates in the United States.

Staphylococcus aureus capsular polysaccharides (CP) are important virulence factors under evaluation as vaccine antigens. Clinical S. aureus isolates have the biosynthetic capability to express either CP5 or CP8 and an understanding of the relationship between CP genotype/phenotype and S. aureus epidemiology is valuable. Using whole genome sequencing, the clonal relatedness and CP genotype were evaluated for disease-associated S. aureus isolates selected from the Tigecycline Evaluation and Surveillance Trial (T.E.S.T) to represent different geographic regions in the United States (US) during 2004 and 2009-10. Thirteen prominent clonal complexes (CC) were identified, with CC5, 8, 30 and 45 representing >80% of disease isolates. CC5 and CC8 isolates were CP type 5 and, CC30 and CC45 isolates were CP type 8. Representative isolates from prevalent CC were susceptible to in vitro opsonophagocytic killing elicited by anti-CP antibodies, demonstrating that susceptibility to opsonic killing is not linked to the genetic lineage. However, as not all S. aureus isolates may express CP, isolates representing the diversity of disease isolates were assessed for CP production. While approximately 35% of isolates (primarily CC8) did not express CP in vitro, CP expression could be clearly demonstrated in vivo for 77% of a subset of these isolates (n = 20) despite the presence of mutations within the capsule operon. CP expression in vivo was also confirmed indirectly by measuring an increase in CP specific antibodies in mice infected with CP5 or CP8 isolates. Detection of antigen expression in vivo in relevant disease states is important to support the inclusion of these antigens in vaccines. Our findings confirm the validity of CP as vaccine targets and the potential of CP-based vaccines to contribute to S. aureus disease prevention.

Effect of Aqueous Extract of Glycyrrhiza glabra on the Biochemical Changes Induced by Cadmium Chloride in Rats.

Twenty four rats were divided into four groups (6 rats/group): 1-control group; 2-licorice (Glycyrrhiza glabra) extract: rats administered with an oral dose of licorice (3 mg/ml/kg/day) using stomach tube for 4 weeks; 3-cadmium chloride group: rats administered with an oral dose of CdCl2 (10 mg/kg/day) using stomach tube for 4 weeks; and 4-licorice extract + CdCl2 group: rats administered orally with both licorice (3 mg/ml/kg/day) and CdCl2 (10 mg/kg/day) using stomach tube for 4 weeks. Administration of CdCl2 induced significant increase in thiobarbituric acid reactive substance (TBARS), paraoxonase-1 (proxon-1), caspase-3 (casp-3) activities, and significant decrease in superoxide dismutase (SOD), catalase (CAT) activities, and glutathione (GSH) content in hepatic tissue. Significant increase in TBARS and kidney injury molecule-1 (KIM-1) and significant decrease in SOD, CAT activities, and GSH content in renal tissue were recorded. Significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) activities, urea, creatinine, and significant decrease in butyryl choline esterase (BChE), total triiodothyronine (T3), and total thyroxin (T4) were recorded in serum. Histological investigation of renal cells showed vacuolations of endothelium lining glomerular tuffs and vacuolations of epithelium lining renal tubules. Investigation of ovarian tissue showed dilatation of interstitial blood vessels and congestion of multiple corpus luteum in CdCl2-treated rats. Significant improvements in the biochemical and histological changes were observed in CdCl2 + licorice extract group. It could be concluded that licorice extract alleviates the hazardous effects of cadmium chloride, which may be attributed to its antioxidant properties.

Role of ethanolic extract of Morus alba leaves on some biochemical and hematological alterations in irradiated male rats.

PURPOSE: The present study aimed to evaluate the protective role of "Morus alba Linn (Family: Moraceae) commonly known as mulberry" leaves extract against hazardous effects of gamma rays in male rats. MATERIALS AND METHODS: Thirty six male albino rats were divided into six groups (six rats/group); (1) control group received 1 ml distilled water, (2) low dose of extract (100 mg/kg) group treated daily with low oral dose of ethanolic extract of mulberry leaves (100 mg/kg body weight (b.wt.)) for 21 consecutive days, (3) high dose of extract (200 mg/kg) group treated daily with high oral dose of ethanolic extract of mulberry leaves (200 mg/kg b.wt.) for the same period, (4) irradiated group rats were subjected to whole body gamma irradiation at a shot dose of 7 Gy, (5) low dose of extract + irradiated group treated daily with low oral dose of ethanolic extract of mulberry leaves (100 mg/kg b.wt.) for 21 consecutive days then rats were exposed to gamma irradiation at a single dose of 7 Gy, (6) high dose of extract + irradiation group treated daily with high oral dose of ethanolic extract of mulberry leaves (200 mg/kg b.wt.) for 21 consecutive days then rats were exposed to gamma irradiation at a single dose of 7 Gy. Rats were sacrificed 1, 7, 15 days post gamma irradiation in all groups. Blood samples were taken at three intervals time in the six groups. RESULTS: The results showed that whole body irradiation of rats induced significant decrease (p < 0.05) in red blood cells (RBCs), hemoglobin (Hb), hematocrit percentage (HCT%), platelet, white blood cells (WBCs), lymphocytes, neutrophils, serum glucose-6-phosphate dehydrogenase (G-6-PD) and insulin. The data also showed significant increase (p < 0.05) in serum total lipids, phospholipids, cholesterol, triglycerides, lactate dehydrogenase (LDH), creatine kinase (CK), and plasma glucose. Administration of mulberry leaves extract, either low or high concentrations to rats prior to irradiation caused significant improvement in the studied parameters. CONCLUSIONS: Mulberry leaves extract prior to exposure to gamma irradiation has radio protector against hazardous effect of irradiation in male rats.

Protective Effect of Origanum Oil on Alterations of Some Trace Elements and Antioxidant Levels Induced by Mercuric Chloride in Male Rats.

In the current study, 48 male rats were classified into four groups (12 rats/group): 1-control group received 1 ml distilled water, 2-origanum oil group treated daily with oral dose of origanum oil (5 mg/kg) for 30 and 60 days, 3-mercuric chloride group treated daily with oral dose of mercuric chloride (4 mg/kg) for 30 and 60 days, and 4-origanum oil + mercuric chloride group treated with both origanum oil and mercuric chloride (5 and 4 mg/kg, respectively) for 30 and 60 days. All treatments were carried out by stomach tube. The results showed that administration of mercuric chloride induced significant increase in thiobarbituric acid reactive substance (TBARS) and decrease in glutathione (GSH), catalase (CAT), and super oxide dismutase (SOD) in testis and spleen tissues. The data also showed significant increase in tumor necrossis factor-α (TNF-α), 8-hydroxy deoxyguanosine (8-OHDG), acid phosphatase (ACP), urea, and creatinine. Furthermore, significant decreases in serum zinc (Zn), copper (Cu), magnesium (Mg), iron (Fe), and testosterone in mercuric chloride group were recorded. The histological examination of testis and spleen tissues showed some degenerative changes while significant improvement in the antioxidant levels, biochemical, trace elements, and histological changes were observed in mercuric chloride group treated with origanum oil. It could be concluded that origanum oil through its antioxidant potential may possess health promoting properties and could protect cells from oxidative damage induced by mercuric chloride.