Antimicrobial resistance among pregnant women with urinary tract infections is on rise: Findings from meta-analysis of observational studies.

Pregnant women have a higher risk of urinary tract infections (UTIs) compared to non-pregnant women, making antibiotics necessary for treatment. However, prescribing antibiotics without culture and sensitivity tests may contribute to antimicrobial resistance. A meta-analysis using R was conducted to determine the prevalence of antibiotic resistance patterns in UTIs among pregnant women. We identified observational studies published in the last 10 years and used a random effects model to calculate the pooled prevalence. The prevalence of Gram-negative organisms causing UTIs in pregnant women was 67 %, while Gram-positive organisms were 22 %. The burden of Gram-positive organisms exhibiting antimicrobial resistance was very high at 95 %, primarily to ampicillin. The most common Gram-negative organisms exhibiting antimicrobial resistance were E. coli, Klebsiella, and Pseudomonas aeruginosa, while the most common Gram-positive organisms resistant to antibiotics were Staphylococcus aureus and coagulase-negative Staphylococcus. Sensitivity and culture testing are recommended for effective treatment in pregnant women with UTIs.

Prevalence of Carbapenem Non-susceptible Gram-Negative Bacteria at Tertiary Care Hospitals in Saudi Arabia.

Background Antibiotics significantly increased life expectancy and decreased mortality rates due to infections. However, this trend is starting to fade with the rise of multidrug-resistant organisms (MDR); these strains are becoming a global burden on healthcare and the economy. The dramatic increase and spread of carbapenem-resistant gram-negative bacteria (CRGNB) has become a serious global public health concern. In this retrospective cross-sectional study, we aimed to estimate the rates of gram-negative bacteremia in five tertiary care hospitals in different geographical locations in Saudi Arabia for five years. Methods A retrospective cross-sectional study was conducted in five tertiary care hospitals in Saudi Arabia among patients with bacteremia due to CRGNB. Electronic medical records were used to retrieve data regarding patient demographics and antimicrobial susceptibility testing (AST) over five years between January 2016 and December 2020. Patients with positive blood cultures for carbapenem-resistant Escherichia (E.) coli, Klebsiella (K.) pneumonia, Pseudomonas (P.) aeruginosa, and Acinetobacter (A.) baumannii comprise the final study population. Results This retrospective multicentric study was conducted between 2016 and 2020 in five tertiary care hospitals across five cities in Saudi Arabia. E. coli (n=2190, 38.03%), K. pneumoniae (n=2154, 37.41%), P. aeruginosa (n = 918, 15.94%), and A. baumannii (n=496, 8.61%) constitute the 5758 gram-negative bacteria isolates. E. coli was the most frequently identified species in Riyadh, AlAhsa, Dammam, and Madinah (40%, 46.50%, 61.67%, and 43.66%, respectively), with a p-value of (p<0.001), except in Jeddah, where K. pneumoniae was the most prevalent (42%). The mean age of patients across Riyadh, AlAhsa, Dammam, and Madinah was 62.2 years (± 4.24). In contrast to Jeddah, where the majority of isolates (702; 41.8%) belonged to the adult age group. Most isolates were from male patients (3045; 52.9%), compared to 2713 (47.1%) from female patients. K. pneumoniae 1226 (40.3%) was the most prevalent isolate among male patients while E. coli (1135; 41.8%) was the most prevalent isolate among female patients. Conclusion Our study showed that the prevalence of carbapenem non-susceptible Gram-negative bacteria is relatively high, which therefore makes them very challenging to treat. The results show an urgent need for improved antibiotic stewardship strategies, including better surveillance and more effective infection control measures to reduce this issue. Further research into the molecular epidemiology and risk factors associated with these infections is necessary to guide public health policymakers in developing interventions to help control the spread of carbapenem-resistant Gram-negative bacteria.

Antimicrobial resistance trends of non-fermenter Gram negative bacteria in Saudi Arabia: A six-year national study.

BACKGROUND: Antimicrobial resistance (AMR) of non-fermenting Gram-negative bacteria (NFGNB) is increasingly recognized as urgent healthcare threat. Trend data on AMR of NFGNB in Saudi Arabia are either old or limited. The objective was to estimate the prevalence and resistance trends of isolated NFGNB in Saudi Arabia. METHODS: A retrospective multicenter study involving seven tertiary care hospitals in Saudi Arabia was conducted between 2011 and 2016. Susceptibility testing for non-duplicate isolates was performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines in College of American Pathologists accredited diagnostic microbiology laboratories in the participating hospitals. RESULTS: Out of 461,274 isolates, 100,132 (21.7%) were NFGNB which represented 30% of gram-negative pathogens. Pseudomonas aeruginosa was the most common (73.6%), followed by Acinetobacter baumannii (21.0%) and Stenotrophomonas maltophilia (5.3%). Resistance trends of P. aeruginosa were increasing for aztreonam (absolute increase during the study was 17.3%), imipenem (12.3%), and meropenem (11.6%). A. baumannii was fully resistant to several beta lactam drugs, and resistance trends were increasing for potential treatments such as tigecycline (25.1%) and tobramycin (15.5%). S. maltophilia was >90% resistant to trimethoprim/ sulfamethoxazole and ciprofloxacin by the end of the study. CONCLUSION: We are reporting high and/or increasing resistance of NFGNB to common treatment options. The current findings call for urgent actions to combat the increasing resistance of NFGNB. Large scale sharing of AMR data collected at different hospitals with the Saudi AMR committee would be critical to set priorities and monitor progress.

A retrospective evaluation of the value of COVID-19 screening and testing in patients with cancer: Aiming at a moving target.

BACKGROUND: Diagnosis of COVID-19 infection in cancer patients is critical to co-manage their underlying disease and infection appropriately. Our study aimed at evaluating the sensitivity and specificity of screening patients with cancer for COVID-19 infection. METHODS: All oncology patients receiving care at Department of Oncology at King Abdulaziz Medical City in Riyadh were screened using the acute respiratory infection (ARI) survey. Nasopharyngeal and throat swap for polymerase chain reaction (PCR) testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was performed on patients who have high ARI score (i.e. ≥ 4), or any patient requiring elective/emergency hospitalization, undergoing a procedure as well as screening asymptomatic patients receiving chemotherapy between April 1st and July 30, 2020. Institutional Review Board approval was obtained. Descriptive and inferential analyses were done and sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated considering the COVID-19 PCR as the gold standard. RESULTS: During the study period, a total of 473 patients were included with a median age was 56 years (14-104), 51% were female, 73% had solid tumors, and 66% received treatment within the last 3 months. These patients underwent 688 PCR tests along with ARI survey screening. Testing was done in the outpatient, inpatient, and emergency department setting in 41%, 40% and 19% of the patients, respectively. Majority of tests were screening of asymptomatic patients and only 23% were tested for suspected infections with ARI ≥ 4. A total of 54 patients (8%) had positive PCR for COVID-19 infection. The prevalence of infection varied from month to month ranging from 1.09% in April up to 19.70% in June and correlated with the average daily and active case load at a national level. The diagnostic yield of the ARI score also correlated with infection burden nationally. The PPV and NPV of the ARI as a screening tool was 18.24% (0-31.8) and 95.6% (86.36-98.86%) with the PPN fluctuating considerably in parallel with the prevalence of COVID-19 result. Similarly, the sensitivity and specificity of the ARI were 55.77% (0-70.59) and 79.4 (69.19-92), respectively. CONCLUSION: The yield of screening asymptomatic patients with cancer varies based on the community burden of COVID-19 infection. As universal screening can cause delays to patient care, it should be tailored based on the individual patient risks and infection burden in the region.

SARS-CoV-2 infection in children, clinical characteristics, diagnostic findings and therapeutic interventions at a tertiary care center in Riyadh, Saudi Arabia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 was first identified in Wuhan, China. All ages are susceptible to SARS-CoV-2 infection. Few studies had reported milder course in children however, severe course of illness has been reported. We aimed to describe the clinical features of COVID-19 in pediatric patients including diagnostic findings and therapeutic interventions in sever disease manifestation. METHODS: We retrospectively reviewed 742 patients with SARS-CoV-2 proven infection at King Abdullah Specialist Children's Hospital, from April 2020 and July 2020. Inpatients, outpatient, including those with sever manifestation treated at the Intensive Care Unit (ICU) were included. We collected data including demographic data, comorbidities, symptoms, imaging data, laboratory findings, treatments and clinical outcomes of patients with COVID-19. RESULTS: Among of 742 patients, 71 (9.6%) were hospitalized. The median age of patients was 75 months old and 53.6 were male. A total of 461 (62.1%) had close contact with confirmed cases, 45 (6.1%) had no contact history, and 236 (31.8%) with unknown exposure risk. The most common symptoms at the onset of illness were fever (32.5%), respiratory symptoms (21%) and gastrointestinal symptoms (10.3%). Among the entire cohort, 7 patients were admitted to PICU with COVID-19 related symptoms, five patients diagnosed with MIS-C, one patient with Kawasaki, and one patient with pneumonia. All patients received supportive therapy, no antiviral treatment had been used however, in MIS-C patients IVIG had been given to all patients, five patients received Anakinra; and one patient received tocilizumab. CONCLUSIONS: In this study, children infected with SARS-CoV-2 are less likely to develop symptomatic or serious diseases. Among symptomatic children, the most common clinical features were fever and respiratory symptoms followed by gastrointestinal manifestations. The majority of infected children have reported contact with an infected individual. MIS-C associated with COVID-19 is a severe presentation of SARS-CoV-2 infection and of a major concern as an overlapping features with other diseases could happen, making the diagnosis challenging.

Management of Candida auris outbreak in a tertiary-care setting in Saudi Arabia.

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.

Invasive Candidiasis in Critically Ill Patients: A Prospective Cohort Study in Two Tertiary Care Centers.

BACKGROUND: Invasive candidiasis is not uncommon in critically ill patients but has variable epidemiology and outcomes between intensive care units (ICUs). This study evaluated the epidemiology, characteristics, management, and outcomes of patients with invasive candidiasis at 6 ICUs of 2 tertiary care centers. METHODS: This was a prospective observational study of all adults admitted to 6 ICUs in 2 different hospitals between August 2012 and May 2016 and diagnosed to have invasive candidiasis by 2 intensivists according to predefined criteria. The epidemiology of isolated Candida and the characteristics, management, and outcomes of affected patients were studied. Multivariable logistic regression analyses were performed to identify the predictors of non-albicans versus albicans infection and hospital mortality. RESULTS: Invasive candidiasis was diagnosed in 162 (age 58.4 ± 18.9 years, 52.2% males, 82.1% medical admissions, and admission Acute Physiology and Chronic Health Evaluation II score 24.1 ± 8.4) patients at a rate of 2.6 cases per 100 ICU admissions. On the diagnosis day, the Candida score was 2.4 ± 0.9 in invasive candidiasis compared with 1.6 ± 0.9 in Candida colonization (P < .01). The most frequent species were albicans (38.3%), tropicalis (16.7%), glabrata (16%), and parapsilosis (13.6%). In patients with candidemia, antifungal therapy was started on average 1 hour before knowing the culture result (59.6% of therapy initiated after). Resistance to fluconazole, caspofungin, and amphotericin B occurred in 27.9%, 2.9%, and 3.1%, respectively. The hospital mortality was 58.6% with no difference between albicans and non-albicans infections (61.3% and 54.9%, respectively; P = .44). The independent predictors of mortality were renal replacement therapy after invasive candidiasis diagnosis (odds ratio: 5.42; 95% confidence interval: 2.16-13.56) and invasive candidiasis leading/contributing to ICU admission versus occurring during critical illness (odds ratio: 2.87; 95% confidence interval: 1.22-6.74). CONCLUSIONS: In critically ill patients with invasive candidiasis, non-albicans was responsible for most cases, and mortality was high (58.6%). Antifungal therapy was initiated after culture results in 60% suggesting low preclinical suspicion. Study registration: NCT01490684; registered in ClinicalTrials.gov on February 11, 2012.

Complete Genome Sequence of a Colistin-Resistant Uropathogenic Escherichia coli Sequence Type 131 fimH22 Strain Harboring mcr-1 on an IncHI2 Plasmid, Isolated in Riyadh, Saudi Arabia.

We report the complete genome sequence of a colistin-resistant strain of uropathogenic Escherichia coli, isolated in January 2013 at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. The isolate (named SA186) was sequence type 131 (ST131) and belonged to serotype O25b-H4 and clade B (fimH22).

Mycobacterium riyadhense as the opportunistic infection that lead to HIV diagnosis: A report of 2 cases and literature review.

Human immunodeficiency virus (HIV) infection usually presents with a wide range of manifestations. Although HIV patients are prone to pulmonary infections by opportunistic pathogens in the late stage of AIDS, manifesting the disease with pulmonary infections caused by Mycobacterium riyadhense (newly identified non-tuberculous mycobacteria) is extremely rare with only one case reported in the literature. We are describing two previously healthy patients who presented with M. riyadhense lung infection and were subsequently found to have HIV, illustrating the need for considering the possibility M. riyadhense lung infection as a presenting illness of HIV.

High Prevalence of MERS-CoV Infection in Camel Workers in Saudi Arabia.

Middle East respiratory syndrome (MERS), a highly lethal respiratory disease caused by a novel coronavirus (MERS-CoV), is an emerging disease with high potential for epidemic spread. It has been listed by the WHO and the Coalition for Epidemic Preparedness Innovations (CEPI) as an important target for vaccine development. While initially the majority of MERS cases were hospital acquired, continued emergence of MERS is attributed to community acquisition, with camels likely being the direct or indirect source. However, the majority of patients do not describe camel exposure, making the route of transmission unclear. Here, using sensitive immunological assays and a cohort of camel workers (CWs) with well-documented camel exposure, we show that approximately 50% of camel workers (CWs) in the Kingdom of Saudi Arabia (KSA) and 0% of controls were previously infected. We obtained blood samples from 30 camel herders, truck drivers, and handlers with well-documented camel exposure and from healthy donors, and measured MERS-CoV-specific enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay (IFA), and neutralizing antibody titers, as well as T cell responses. Totals of 16/30 CWs and 0/30 healthy control donors were seropositive by MERS-CoV-specific ELISA and/or neutralizing antibody titer, and an additional four CWs were seronegative but contained virus-specific T cells in their blood. Although virus transmission from CWs has not been formally demonstrated, a possible explanation for repeated MERS outbreaks is that CWs develop mild disease and then transmit the virus to uninfected individuals. Infection of some of these individuals, such as those with comorbidities, results in severe disease and in the episodic appearance of patients with MERS.IMPORTANCE The Middle East respiratory syndrome (MERS) is a coronavirus (CoV)-mediated respiratory disease. Virus transmission occurs within health care settings, but cases also appear sporadically in the community. Camels are believed to be the source for community-acquired cases, but most patients do not have camel exposure. Here, we assessed whether camel workers (CWs) with high rates of exposure to camel nasal and oral secretions had evidence of MERS-CoV infection. The results indicate that a high percentage of CWs were positive for virus-specific immune responses but had no history of significant respiratory disease. Thus, a possible explanation for repeated MERS outbreaks is that CWs develop mild or subclinical disease. These CWs then transmit the virus to uninfected individuals, some of whom are highly susceptible, develop severe disease, and are detected as primary MERS cases in the community.

Identification of carbapenem-resistant Pseudomonas aeruginosa in selected hospitals of the Gulf Cooperation Council States: dominance of high-risk clones in the region.

PURPOSE: The molecular epidemiology and resistance mechanisms of carbapenem-resistant Pseudomonas aeruginosa (CRPA) were determined in hospitals in the countries of the Gulf Cooperation Council (GCC), namely, Saudi Arabia, the United Arab Emirates, Oman, Qatar, Bahrain and Kuwait. METHODOLOGY: Isolates were screened for common carbapenem-resistance genes by PCR. Relatedness between isolates was assessed using previously described genotyping methods: an informative-single nucleotide polymorphism MassARRAY iPLEX assay (iPLEX20SNP) and the enterobacterial repetitive intergenic consensus (ERIC)-PCR assay, with selected isolates being subjected to multilocus sequence typing (MLST). Ninety-five non-repetitive isolates that were found to be resistant to carbapenems were subjected to further investigation.Results/Key findings. The most prevalent carbapenemase-encoding gene, blaVIM-type, was found in 37/95 (39 %) isolates, while only 1 isolate (from UAE) was found to have blaIMP-type. None of the CRPA were found to have blaNDM-type or blaKPC-type. We found a total of 14 sequence type (ST) clusters, with 4 of these clusters being observed in more than 1 country. Several clusters belonged to the previously recognized internationally disseminated high-risk clones ST357, ST235, ST111, ST233 and ST654. We also found the less predominant ST316, ST308 and ST823 clones, and novel MLST types (ST2010, ST2011, ST2012 and ST2013), in our collection. CONCLUSION: Overall our data show that 'high-risk' CRPA clones are now detected in the region and highlight the need for strategies to limit further spread of such organisms, including enhanced surveillance, infection control precautions and further promotion of antibiotic stewardship programmes.

Recovery from the Middle East respiratory syndrome is associated with antibody and T-cell responses.

The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pneumonia. MERS was recently identified as a candidate for vaccine development, but most efforts focus on antibody responses, which are often transient after CoV infections. CoV-specific T cells are generally long-lived, but the virus-specific T cell response has not been addressed in MERS patients. We obtained peripheral blood mononuclear cells and/or sera from 21 MERS survivors. We detected MERS-CoV-specific CD4+ and CD8+ T cell responses in all MERS survivors and demonstrated functionality by measuring cytokine expression after peptide stimulation. Neutralizing (PRNT50) antibody titers measured in vitro predicted serum protective ability in infected mice and correlated with CD4+ but not CD8+ T cell responses; patients with higher PRNT50 and CD4+ T cell responses had longer intensive care unit stays and prolonged virus shedding and required ventilation. Survivors with undetectable MERS-CoV-specific antibody responses mounted CD8+ T cell responses comparable with those of the whole cohort. There were no correlations between age, disease severity, comorbidities, and virus-specific CD8+ T cell responses. In conclusion, measurements of MERS-CoV-specific T cell responses may be useful for predicting prognosis, monitoring vaccine efficacy, and identifying MERS patients with mild disease in epidemiological studies and will complement virus-specific antibody measurements.

Identified Transmission Dynamics of Middle East Respiratory Syndrome Coronavirus Infection During an Outbreak: Implications of an Overcrowded Emergency Department.

A total 130 cases of Middle East respiratory syndrome coronavirus were identified during a large hospital outbreak in Saudi Arabia; 87 patients and 43 healthcare workers. The majority (80%) of transmission was healthcare-acquired (HAI) infection, with 4 generations of HAI transmission. The emergency department was the main location of exposure.

Impact of empirical antimicrobial therapy on the outcome of critically ill patients with Acinetobacter bacteremia.

RATIONALE: Empirical antimicrobial therapy (EAT) for Acinetobacter infections may not be appropriate as it tends to be multidrug-resistant. This study evaluated the relationship between appropriate EAT and the outcomes of Intensive Care Unit (ICU) patients with Acinetobacter bacteremia. METHODS: This is a retrospective study of patients admitted to a medical-surgical ICU (2005-2010) and developed Acinetobacter bacteremia during the stay. Patients were categorized according to EAT appropriateness, defined as administration of at least one antimicrobial agent to which the Acinetobacter was susceptible before susceptibility results were known. The relation between EAT appropriateness and outcomes was evaluated. RESULTS: Sixty patients developed Acinetobacter bacteremia in the 6-year period (age = 50 ± 19 years; 62% males; Acute Physiology and Chronic Health Evaluation II score = 28 ± 9; 98.3% with central lines; 67% in shock and 59% mechanically ventilated) on average on day 23 of ICU and day 38 of hospital stay. All isolates were resistant to at least three of the tested antimicrobials. Appropriate EAT was administered to 60% of patients, mostly as intravenous colistin. Appropriate EAT was associated with lower ICU mortality risk (odds ratio: 0.15; 95% confidence interval: 0.03-0.96) on multivariate analysis. CONCLUSIONS: In this 6-year cohort, Acinetobacter bacteremia was related to multidrug-resistant strains. Appropriate EAT was associated with decreased ICU mortality risk.

Antibiotic-resistant ST38, ST131 and ST405 strains are the leading uropathogenic Escherichia coli clones in Riyadh, Saudi Arabia.

OBJECTIVES: We investigated the molecular epidemiology of uropathogenic Escherichia coli (UPEC) from a tertiary care hospital in Riyadh, Saudi Arabia, revealing, for the first time, the population structure of UPEC in the region. METHODS: A total of 202 UPEC isolates were recovered from hospital and community patients with urinary tract infection in December 2012 and January 2013. Strains were characterized by MLST, antibiotic susceptibility determination and virulence gene detection. RESULTS: The most common lineages were ST131 (17.3%), ST73 (11.4%), ST38 (7.4%), ST69 (7.4%), ST10 (6.4%), ST127 (5.9%), ST95 (5.4%), ST12 (3.5%), ST998 (3.5%) and ST405 (3%). ST131 and ST405 isolates were significantly associated with high levels of antibiotic resistance (60% of ST131 carried CTX-M-14 or CTX-M-15 and 66.7% of ST405 isolates carried CTX-M-15). ST131, CTX-M-15-positive isolates were predominantly of the fimH30/clade C group, resistant to fluoroquinolones; members of this sub-group were more likely to carry a high number of genes encoding selected virulence determinants. The relatively high proportion of ST38 was notable and four of these isolates harboured aggR. CONCLUSIONS: 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.

Molecular epidemiology of carbapenem-resistant Acinetobacter baumannii isolates in the Gulf Cooperation Council States: dominance of OXA-23-type producers.

The molecular epidemiology and mechanisms of resistance of carbapenem-resistant Acinetobacter baumannii (CRAB) were determined in hospitals in the states of the Cooperation Council for the Arab States of the Gulf (Gulf Cooperation Council [GCC]), namely, Saudi Arabia, United Arab Emirates, Oman, Qatar, Bahrain, and Kuwait. Isolates were subjected to PCR-based detection of antibiotic resistance genes and repetitive sequence-based PCR (rep-PCR) assessments of clonality. Selected isolates were subjected to multilocus sequence typing (MLST). We investigated 117 isolates resistant to carbapenem antibiotics (either imipenem or meropenem). All isolates were positive for OXA-51. The most common carbapenemases were the OXA-23-type, found in 107 isolates, followed by OXA-40-type (OXA-24-type), found in 5 isolates; 3 isolates carried the ISAba1 element upstream of blaOXA-51-type. No OXA-58-type, NDM-type, VIM-type, or IMP-type producers were detected. Multiple clones were detected with 16 clusters of clonally related CRAB. Some clusters involved hospitals in different states. MLST analysis of 15 representative isolates from different clusters identified seven different sequence types (ST195, ST208, ST229, ST436, ST450, ST452, and ST499), as well as three novel STs. The vast majority (84%) of the isolates in this study were associated with health care exposure. Awareness of multidrug-resistant organisms in GCC states has important implications for optimizing infection control practices; establishing antimicrobial stewardship programs within hospital, community, and agricultural settings; and emphasizing the need for establishing regional active surveillance systems. This will help to control the spread of CRAB in the Middle East and in hospitals accommodating transferred patients from this region.

Multi-drug carbapenem-resistant Klebsiella pneumoniae infection carrying the OXA-48 gene and showing variations in outer membrane protein 36 causing an outbreak in a tertiary care hospital in Riyadh, Saudi Arabia.

OBJECTIVES: To investigate the genes of antibiotic resistance among isolates from the first reported carbapenem-resistant Klebsiella pneumoniae (CRKP) outbreak in a tertiary care hospital, Riyadh, Saudi Arabia. METHODS: Antimicrobial susceptibility testing was performed on bacterial isolates using the Microscan Walkaway system (Siemens, Germany) and was confirmed by Etest (AB Biodisk, Sweden). bla-CTX-M, -SHV, -TEM, -OXA-48, OXA-A,B,C,D, -KPC, -NDM, -VIM, -IMP, integron 1, and outer membrane proteins(Omp)-35 and Omp-36 were investigated by PCR amplification and direct sequencing of PCR products. Isolates were sequence-typed by multilocus sequence typing (MLST). RESULTS: All isolates were resistant to cefotaxime, ceftazidime, cefepime, ciprofloxacin, and piperacillin-tazobactam, and 91% (21 out of 23) were resistant to amikacin and gentamicin. All isolates except two from a single patient were resistant to one of the carbapenems. CTX-M and SHV genes were detected in all isolates, CTX-M-15 and SHV-1 types being predominant among these extended-spectrum beta-lactamases (ESBLs). TEM-1 was found in all except one isolate (isolate 3). Significantly, the OXA-48 gene was also found in all isolates. OXA-D-gene was found in three out of 23 isolates. KPC, NDM, OXA-A, -B, -C, VIM, and IMP genes were absent in all isolates. Disruption of the Omp-36 gene due to insertion of transposon IS903 and/or IS4 was detected in four out of 23 isolates, and some unique variations were also observed in this gene, including an insertion of two amino acids in the L3 region of Omp-36 in one isolate (isolate 3) and a mutation resulting in a premature stop codon in another isolate (isolate 25). MLST revealed ST29 to be the predominant sequence type (17 out of 23 isolates, 74%). Three were ST709 and one each was ST37 and ST111; one isolate had an unknown ST. CONCLUSIONS: This is probably the first reported outbreak of multidrug/carbapenem-resistant Klebsiella infection involving the OXA-48 gene from Saudi Arabia. Although the presence of ESBLs such as OXA, CTX-M, TEM, and SHV are predictable reasons for resistance, variations in the Omp-36 gene might also have precipitated this phenomenon. Disruption of the Omp-36 sequence by large insertional elements, the insertion of two amino acids in a very crucial part of this protein, and the presence of a premature stop codon in one isolate might have rendered this protein incomplete and non-functional. The study also demonstrated that more than one type of clone was responsible for this reported apparent outbreak and that ST29, a clone not reported from this region before, was the major clone responsible.

Molecular characterization of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in the countries of the Gulf cooperation council: dominance of OXA-48 and NDM producers.

The molecular epidemiology and mechanisms of resistance of carbapenem-resistant Enterobacteriaceae (CRE) were determined in hospitals in the countries of the Gulf Cooperation Council (GCC), namely, Saudi Arabia, United Arab Emirates, Oman, Qatar, Bahrain, and Kuwait. Isolates were subjected to PCR-based detection of antibiotic-resistant genes and repetitive sequence-based PCR (rep-PCR) assessments of clonality. Sixty-two isolates which screened positive for potential carbapenemase production were assessed, and 45 were found to produce carbapenemase. The most common carbapenemases were of the OXA-48 (35 isolates) and NDM (16 isolates) types; 6 isolates were found to coproduce the OXA-48 and NDM types. No KPC-type, VIM-type, or IMP-type producers were detected. Multiple clones were detected with seven clusters of clonally related Klebsiella pneumoniae. Awareness of CRE in GCC countries has important implications for controlling the spread of CRE in the Middle East and in hospitals accommodating patients transferred from the region.

Prevalence of antimicrobial resistance among gram-negative isolates in an adult intensive care unit at a tertiary care center in Saudi Arabia.

BACKGROUND AND OBJECTIVES: Patients in the ICU have encountered an increasing emergence and spread of antibiotic-resistant pathogens. We examined patterns of antimicrobial susceptibility in gram-negative isolates to commonly used drugs in an adult ICU at a tertiary care hospital in Riyadh, Saudi Arabia. METHODS: A retrospective study was carried out of gram-negative isolates from the adult ICU of King Fahad National Guard Hospital (KFNGH) between 2004 and 2009. Organisms were identified and tested by an automated identification and susceptibility system, and the antibiotic susceptibility testing was confirmed by the disk diffusion method. RESULTS: The most frequently isolated organism was Acinetobacter baumannii, followed by Pseudomonas aeruginosa, Escherichia coli, Klebsiella pnemoniae, Stenotrophomonas maltophilia, and Enterobacter. Antibiotic susceptibility patterns significantly declined in many organisms, especially A baumannii, E coli, S marcescens, and Enterobacter. A baumannii susceptibility was significantly decreased to imipenem (55% to 10%), meropenem (33% to 10%), ciprofloxacin (22% to 10%), and amikacin (12% to 6%). E coli susceptibility was markedly decreased (from 75% to 50% or less) to cefuroxime, ceftazidime, cefotaxime, and cefepime. S marcescens susceptibility was markedly decreased to cefotaxime (100% to 32%), ceftazidime (100% to 35%), and cefepime (100% to 66%). Enterobacter susceptibility was markedly decreased to ceftazidime (34% to 5%), cefotaxime (34% to 6%), and pipracillin-tazobactam (51% to 35%). Respiratory samples were the most frequently indicative of multidrug-resistant pathogens (63%), followed by urinary samples (57%). CONCLUSION: Antimicrobial resistance is an emerging problem in the KFNGH ICU, justifying new more stringent antibiotic prescription guidelines. Continuous monitoring of antimicrobial susceptibility and strict adherence to infection prevention guidelines are essential to eliminate major outbreaks in the future.