Our findings highlight the presence of MDR, CTX-M-positive ST38, ST131 and ST405 UPEC in Saudi Arabia. The high proportion of isolates with CTX-M is a particular concern. We suggest that ST38 UPEC warrant further study.

Galleria mellonella larvae are an alternative in vivo model for investigating bacterial pathogenicity. Here, we examined the pathogenicity of 71 isolates from five leading uropathogenic E. coli (UPEC) lineages using G. mellonella larvae. Larvae were challenged with a range of inoculum doses to determine the 50% lethal dose (LD50) and for analysis of survival outcome using Kaplan-Meier plots. Virulence was correlated with carriage of a panel of 29 virulence factors (VF). Larvae inoculated with ST69 and ST127 isolates (104 colony-forming units/larvae) showed significantly higher mortality rates than those infected with ST73, ST95 and ST131 isolates, killing 50% of the larvae within 24 hours. Interestingly, ST131 isolates were the least virulent. We observed that ST127 isolates are significantly associated with a higher VF-score than isolates of all other STs tested (P≤0.0001), including ST69 (P<0.02), but one ST127 isolate (strain EC18) was avirulent. Comparative genomic analyses with virulent ST127 strains revealed an IS1 mediated deletion in the O-antigen cluster in strain EC18, which is likely to explain the lack of virulence in the larvae infection model. Virulence in the larvae was not correlated with serotype or phylogenetic group. This study illustrates that G. mellonella are an excellent tool for investigation of the virulence of UPEC strains. The findings also support our suggestion that the incidence of ST127 strains should be monitored, as these isolates have not yet been widely reported, but they clearly have a pathogenic potential greater than that of more widely recognised clones, including ST73, ST95 or ST131.

Background: Studying temporal changes in resistant pathogens causing healthcare-associated infections (HAIs) is crucial in improving local antimicrobial and infection control practices. The objective was to describe ten-year trends of resistance in pathogens causing HAIs in a tertiary care setting in Saudi Arabia and to compare such trends with those of US National Health Surveillance Network (NHSN).Methods: Pooled analysis of surveillance data that were prospectively collected between 2007 and 2016 in four hospitals of Ministry of National Guard Health Affairs. Definitions and methodology of HAIs and antimicrobial resistance were based on NHSN. Consecutive NHSN reports were used for comparisons.Results: A total 1544 pathogens causing 1531 HAI events were included. Gram negative pathogens (GNP) were responsible for 63% of HAIs, with a significant increasing trend in Klebsiella spp. and a decreasing trend in Acinetobacter. Methicillin-resistant Staphylococcus aureus (27.0%) was consistently less frequent than NHSN. Vancomycin-resistant Enterococci (VRE, 20.3%) were more than doubled during the study, closing the gap with NHSN. Carbapenem resistance was highest with Acinetobacter (68.3%) and Pseudomonas (36.8%). Increasing trends of carbapenem resistance were highest in Pseudomonas and Enterobacteriaceae, closing initial gaps with NHSN. With the exception of Klebsiella and Enterobacter, multidrug-resistant (MDR) GNPs were generally decreasing, mainly due to the decreasing resistance towards cephalosporins, fluoroquinolones, and aminoglycosides. Conclusion:The findings showed increasing trends of carbapenem resistance and VRE, which may reflect heavy use of carbapenems and vancomycin. These findings may highlight the need for effective antimicrobial stewardship programs, including monitoring and feedback on antimicrobial use and resistance.

BACKGROUND: Carbapenems are the antibiotics of last-resort for the treatment of bacterial infections caused by multidrug-resistant organisms. The emergence of resistance is a critical and worrisome problem for clinicians and patients. Carbapenem-resistant Enterobacterales (CRE) are spreading globally, are associated with an increased frequency of reported outbreaks in many regions, and are becoming endemic in many others. OBJECTIVES: Determine the molecular epidemiology of CRE isolates from various regions of Saudi Arabia to identify the genes encoding resistance and their clones for a better understanding of the epidemio-logical origin and national spread. DESIGN: Multicenter, cross-sectional, laboratory-based study. SETTING: Samples were collected from 13 Ministry of Health tertiary-care hospitals from five different regions of Saudi Arabia. METHODS: Isolates were tested using the GeneXpert molecular platform to classify CRE. MAIN OUTCOME MEASURES: Prevalence of various types of CRE in Saudi Arabia. SAMPLE SIZE: 519 carbapenem-resistant isolates. RESULT: Of 519 isolates, 440 (84.7%) were positive for CRE, with Klebsiella pneumoniae (410/456, 90%) being the most commonly isolated pathogen. The distribution of the CRE-positive K pneumoniae resistance genes was as follows: OXA-48 (n=292, 71.2%), NDM-1 (n=85, 20.7%), and NDM+OXA-48 (n=33, 8%). The highest percentage of a single blaOXA-48 gene was detected in the central and eastern regions (77%), while the bla NDM -gene was the predominant type in the northern region (27%). The southern regions showed the lowest percentages for harboring both blaOXA-48 and bla NDM genes (4%), while the western region isolates showed the highest percentage of harboring both genes (14%). CONCLUSION: The results illustrate the importance of molecular characterization of CRE isolates for patient care and infection prevention and control. Larger multicenter studies are needed to critically evaluate the risk factors and trends over time to understand the dynamics of spread and effective methods of control. LIMITATIONS: Lack of phenotypic susceptibility and clinical data. CONFLICT OF INTEREST: None.

Objective: To describe local experience in managing an outbreak of Candida auris in a tertiary-care setting. Methods: In response to emerging Candida auris, an outbreak investigation was conducted at our hospital between March 2018 and June 2019. Once a patient was confirmed to have Candida auris, screening of exposed patients and healthcare workers (HCWs) was conducted. Postexposure screening included those who had had direct contact with or shared the same unit or ward with a laboratory-confirmed case. In response to the increasing number of cases, new infection control measures were implemented. Results: In total, 23 primary patients were detected over 15 months. Postexposure screening identified 11 more cases, and all were patients. Furthermore, ~28.6% of patients probably caught infection in another hospital or in the community. Infection control measures were strictly implemented including hand hygiene, personal protective equipment, patient hygiene, environmental cleaning, cohorting of patients and HCWs, and avoiding the sharing of equipment. The wave reached a peak in April 2019, followed by a sharp decrease in May 2019 and complete clearance in June 2019. The case patients were equally distributed between intensive care units (51.4%) and wards (48.6%). More infections (62.9%) occurred than colonizations (37.1%). Urinary tract infection (42.9%) and candidemia (17.1%) were the main infections. In total, 7 patients (20.0%) died during hospitalization; among them, 6 (17.1%) died within 30 days of diagnosis. Conclusions: Active screening of exposed patients followed by strict infection control measures, including environmental cleaning, was successful in ending the outbreak. Preventing future outbreaks is challenging due to outside sources of infection and environmental resistance.

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Pandrug-resistant (PDR) K. pneumoniae refractory to conventional treatment has been reported worldwide, causing a huge burden on the healthcare system, patient safety and the economy. K. pneumoniae is a prominent opportunistic pathogen causing hospital-acquired and community-acquired infections, but is rarely associated with infective endocarditis. Currently, there are sparse data guiding the optimal regimen when commonly used antibiotics fail, notably for the treatment of endocarditis infections. Here we report our experience in treating a 40-year-old female with PDR K. pneumoniae infection of cardiovascular implantable electronic device (CIED) and right-sided infective endocarditis. Initial susceptibility testing of the incriminated pathogen showed an apparent susceptibility to colistin but the prolonged course of colistin, gentamicin and meropenem did not resolve the infection. However, the synergistic combinations of aztreonam with ceftazidime-avibactam was able to overcome resistance and clear the infection rapidly. Genome sequencing showed that the PDR K. pneumoniae isolate belongs to the international high-risk clone ST14. The isolate harbored genes encoding NDM-1, OXA-48, CTX-M-14b, SHV-28 and OXA-1, explaining resistance to all β-lactams, including carbapenems. It carried the armA gene conferring resistance to all clinically important aminoglycosides and had alterations in GyrA, ParC and MgrB, explaining resistance to ciprofloxacin and colistin.

The misuse of antibiotics is leading to the emergence of multidrug-resistant (MDR) bacteria, and in the absence of available treatments, this has become a major global threat. In the middle of the recent severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic, which has challenged the whole world, the emergence of MDR bacteria is increasing due to prophylactic administration of antibiotics to intensive care unit patients to prevent secondary bacterial infections. This is just an example underscoring the need to seek alternative treatments against MDR bacteria. To this end, phage therapy has been proposed as a promising tool. However, further research in the field is mandatory to assure safety protocols and to develop appropriate regulations for its use in clinics. This requires investing more in such non-conventional or alternative therapeutic approaches, to develop new treatment regimens capable of reducing the emergence of MDR and preventing future global public health concerns that could lead to incalculable human and economic losses.