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.

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.

Landscape of Multidrug-Resistant Gram-Negative Infections in Egypt: Survey and Literature Review.

PURPOSE: This article is the first to review published reports on the prevalence of multidrug-resistant (MDR) gram-negative infections in Egypt and gain insights into antimicrobial resistance (AMR) surveillance and susceptibility testing capabilities of Egyptian medical centers. MATERIALS AND METHODS: A literature review and online survey were conducted. RESULTS: The online survey and literature review reported high prevalence of extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae (19-85.24% of E. coli, and 10-87% of K. pneumoniae), carbapenem-resistant Enterobacteriaceae (35-100% of K. pneumoniae and 13.8-100% of E. coli), carbapenem-resistant Acinetobacter baumannii (10-100%), and carbapenem-resistant Pseudomonas aeruginosa (15-70%) in Egypt. Risk factors for MDR Gram-negative infections were ventilated patients (67.4%), prolonged hospitalization (53.5%) and chronic disease (34.9%). Although antimicrobial surveillance capabilities were deemed at least moderate in most centers, lack of access to rapid AMR diagnostics, lack of use of local epidemiological data in treatment decision-making, lack of antimicrobial stewardship (AMS) programs, and lack of risk prediction tools were commonly reported by respondents. CONCLUSION: This survey has highlighted the presence of knowledge gaps as well as limitations in the surveillance and monitoring capabilities of AMR in Egypt, with most laboratories lacking rapid diagnostics and molecular testing. Future efforts in Egypt should focus on tackling these issues via nationwide initiatives, including understanding the AMR trends in the country, capacity building of laboratories and their staff to correctly and timely identify AMR, and introducing newer antimicrobials for targeting emerging resistance mechanisms in Gram-negative species.

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.

Prevalence of infections and antimicrobial use in the acute-care hospital setting in the Middle East: Results from the first point-prevalence survey in the region.

OBJECTIVES: Community-acquired (CAIs) and healthcare-associated (HAIs) infections are associated with significant morbidity and mortality. Data related to the epidemiology of these infections in the Middle East is scarce. The aim of this study is to estimate the prevalence of infections and antimicrobial use in the acute hospital setting in this region. METHODS: A multicentre Point-Prevalence Survey was conducted in seven Middle Eastern countries: Egypt, Kingdom of Saudi Arabia, United Arab Emirates, Lebanon, Oman, Kuwait and Bahrain. Data were collected by the infection control and infectious diseases teams of the respective hospitals. Study surveys were completed in one day (03 April 2018). RESULTS: The overall point prevalence of infection was 28.3%; HAI and CAI point prevalence was 11.2% and 16.8%, respectively. The majority of patients with an infection (98.2%) were receiving antimicrobial therapy. There were high levels of resistance to antimicrobials among Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumoniae and other Klebsiella sp. CONCLUSIONS: Our findings indicate that the point prevalence of both HAI and CAI is high in a sample of Middle Eastern countries. These findings along with the increased use of antimicrobials represent a significant public health problem in the region; particularly in light of the growing regional antimicrobial resistance.

Treatment of immunocompromised patients with suspected invasive fungal infections: economic analysis of diagnostic-driven versus empirical strategies in Algeria and Egypt.

Background: Invasive fungal infections (IFIs) in immunocompromised patients are associated with high mortality and treatment costs. Identifying appropriate, cost-effective treatment strategies is crucial to reduce the burden of IFIs. This economic assessment compared strategies for treating immunocompromised patients in Algeria and Egypt.Methods: We developed a decision analytic model incorporating clinical and cost inputs associated with a diagnostic-driven (DD) and standard empirical (SE) strategy. Costs and clinical outcomes were used to calculate incremental cost-effectiveness ratios (ICERs) per death avoided.Results: In both countries, 73.8 (DD) and 125.3 (SE) hypothetical patients per 1,000 received antifungal therapy; 73.8 (DD) and 32.7 (SE) had diagnosed IFIs. Survival at 180 days was similar between DD and SE strategies in Algeria (92.0% vs 91.6%) and Egypt (90.2% vs 90.0%). Total costs per patient were lower with the DD than SE strategy (Algeria: $839 vs $1,591; Egypt: $4,077 vs $4,717). ICERs indicated that the DD compared with SE strategy was associated with better clinical outcomes at a lower overall cost in both countries.Conclusion: Diagnostic-driven compared to empirical therapy may be cost-saving in Algeria and Egypt for the management of immunocompromised patients with persistent neutropenic fever, with no increase in mortality.