Clostridioides difficile infections in Saudi Arabia: Where are we standing?

Clostridioides difficile infections (CDIs) are infamous healthcare-associated infections for causing watery diarrhea to long-term hospitalized patients with a high mortality rate. Epidemiological reports from western countries showed up-trending pattern in the number of CDIs cases. It is becoming immensely challenging for routine diagnostic protocols to detect CDIs accurately with short turnaround time. In Saudi Arabia, there is a paucity of data about CDIs' prevalence, recurrence rate, methods of screening and mortality rate. Nevertheless, a growing number of cases with similar virulence strains and comparable antibiotic resistance pattern to the western countries counterparts reported data were also detected. This review aims to present the status of CDIs' diagnosis and incidence rate in Saudi Arabia based on current literature.

Reliability of Haemophilus influenzae biofilm measurement via static method, and determinants of in vitro biofilm production.

Information is lacking regarding the precision of microtitre plate (MTP) assays used to measure biofilm. This study investigated the precision of an MTP assay to measure biofilm production by nontypeable Haemophilus influenzae (NTHi) and the effects of frozen storage and inoculation technique on biofilm production. The density of bacterial final growth was determined by absorbance after 18-20 h incubation, and biofilm production was then measured by absorbance after crystal violet staining. Biofilm formation was categorised as high and low for each strain. For the high biofilm producing strains of NTHi, interday reproducibility of NTHi biofilm formation measured using the MTP assay was excellent and met the acceptance criteria, but higher variability was observed in low biofilm producers. Method of inoculum preparation was a determinant of biofilm formation with inoculum prepared directly from solid media showing increased biofilm production for at least one of the high producing strains. In general, storage of NTHi cultures at -80 °C for up to 48 weeks did not have any major effect on their ability to produce biofilm.

Relationship between clinical site of isolation and ability to form biofilms in vitro in nontypeable Haemophilus influenzae.

Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen associated with a range of infections, including various lower respiratory infections, otitis media, and conjunctivitis. There is some debate as to whether or not NTHi produces biofilms and, if so, whether or not this is relevant to pathogenesis. Although many studies have examined the association between in vitro biofilm formation and isolates from a specific infection type, few have made comparisons from isolates from a broad range of isolates grouped by clinical source. In our study 50 NTHi from different clinical sources, otitis media, conjunctivitis, lower respiratory tract infections in both cystic fibrosis and non-cystic fibrosis patients, and nasopharyngeal carriage, plus 10 nasopharyngeal isolates of the commensal Haemophilus haemolyticus were tested for the ability to form biofilm by using a static microtitre plate crystal violet assay. A high degree of variation in biofilm forming ability was observed across all isolates, with no statistically significant differences observed between the groups, with the exception of the isolates from conjunctivitis. These isolates had uniformly lower biofilm forming ability compared with isolates from the other groups (p < 0.005).

Alternative treatment of recurrent Clostridioides difficile infection in adults by fecal transplantation: an overview of phase I-IV studies from Clinicaltrials.gov.

Background: Fecal microbiota transplantation (FMT) is an interventional approach to treat chronic and recurrent Clostridioides difficile infection (CDI). However, there is insufficient evidence regarding its effectiveness and safety. Clinical trials have been conducted to inspect the safety and effectiveness of FMT with and without comparison to pharmacological treatments. Aim: This review explored the treatment of CDI in adults using FMT and evaluated the safety of this intervention based on phase I-IV studies registered on Clinicaltrials.gov. Method: A comprehensive search of Clinicaltrials.gov was conducted to identify relevant studies that investigated CDI in adults. Data on study type, study design, sample size, intervention details, and outcomes related to FMT were examined and evaluated. Results: In total, 13 clinical trials on FMT for CDI published through 17 November 2023 were identified, all of which were interventional studies. The investigation focused on both terminated and completed studies. Basic and advanced outcome measures were examined. Conclusion: Some studies were terminated during phase II, and FMT was less effective than antibiotics such as vancomycin and fidaxomicin. However, colonoscopy and oral FMT were explored in several completed studies with promising results, but the evidence remains limited and inconclusive.

In Vitro Anticancer and Antibacterial Activities of the Essential Oil of Forsskal's Basil Growing in Extreme Environmental Conditions.

Many species belonging to the genus Ocimum are used for aromatic, medicinal, and cosmetic purposes. The essential oil (OFEO) obtained by hydrodistillation of the flowering aerial parts of Forsskal's Basil "Ocimum forskolei Benth" growing in extreme environmental conditions in Mecca Region, Saudi Arabia was analyzed by GC-MS. The main constituents were phenylpropanoids (methyl eugenol 55.65% and eugenol 11.66%), monoterpene (linalool 9.75%), and sesquiterpenes (germacrene D 3.72% and ß-caryophyllene 2.57%). The OFEO was tested against MCF7, HT29, and HCT116 cancer cells and compared with normal fibroblast cells (MRC5). The MTT assay showed that HCT116 was more sensitive to OFEO (IC50 5.34 µg/mL), which reduced the number of HCT116 colonies at 6 µg/mL, while causing complete colony death at 12 and 24 µg/mL. Western Blotting and qRT-PCR were used to evaluate the level change of different proteins with respect to GAPDH. OFEO upregulated the apoptotic protein (caspase 3), and downregulated the cell proliferation proteins (AKT and pAKT), cell cycle arrest (PCNA, Cyclin D1), and the anti-apoptotic Bcl2 proteins. OFEO was also tested against reference strains of Gram-negative and Gram-positive bacteria including Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, and Staphylococcus aureus by using the well-diffusion and assessing their MICs, which ranged from 250 to 500 µg/mL.

Evaluating the Group Debate Activity as a Student-Centered Approach in Microbiology Course for PharmD Students: An Observational Study.

Background: Group debate is an educational strategy meant to equip undergraduate students with enhanced communication skills as well as the understanding of complex topics. Many controversial topics in the microbiological field pose challenges to the pharmacist's ability to attribute a specific opinion to its supported clinical evidence and to discuss these topics with confidence. Methods: A total of 76 second-year pharmacy students who enrolled in a PharmD program participated in the group debate as part of the student assessment in microbiology course. The students prepared selected topics on controversial issues in microbiology, which were presented as a debate. Post-debate questionnaire was distributed to the students and used to measure student perceptions. Results: The majority of the students (82.89%) demonstrated an improvement in their understanding of the topics after the debate. The highest percentage was recorded from one topic group (97.37%) which stated that they had improved understanding after the debate. About a third of the total students reported great improvement in their communication skills. Conclusion: This debate group clearly provided the students with high confidence in presenting their arguments from relevant scientific information gathered from existing literature. It also enhanced their understanding of complex and controversial microbiology topics that will be needed during their pharmacy education.

The socio-cultural factors behind the Saudi attitude toward COVID-19 vaccination: A survey-based study.

Introduction: Vaccine distrust and rejection are thought to contribute to disease outbreaks and increased mortality. The present study aimed to analyze the socio-cultural characteristics and attitudes of the Saudi population toward vaccines, using a cross-sectional survey-based approach. Methods: An online questionnaire was used, following the snowball method. A total of 444 people responded, of whom 333 (75%) were female, and 111 (25%) were male. Results: The demographic characteristics associated with vaccine confidence were gender, job type, medical problems, and knowledge of coronavirus disease 2019 (COVID-19) symptoms. The hesitancy was highest (31.17%) among individuals aged 21-30 years old, and in more males (27.03%) expressed hesitancy than females (25.23%). However, if we focused on the percentage of the refusal to receive the vaccine, more females (15.23%) refused the vaccine than males (4.5%). More than one-third of the vaccine-hesitant respondents had limited knowledge of COVID-19 symptoms. Personal characteristics associated with vaccine confidence were described as the following: do not fully trust vaccines produced in a short time (42.1%), fear of the future results of the vaccine (30.4%), reluctance to allow a foreign material to enter the body (17.6%), no interaction with others, so no need for the vaccine (11.5%), low interaction with people (67.8%), and reluctance to make decisions (11.3%). The primary social motivation for getting the vaccine was to get back to normal life (67.6%). Discussion: The results of the present study revealed that more than half of the respondents in Saudi Arabia were confident about the vaccine (61.7%), while only 25.7% were hesitant and 12.6% were unconvinced. Based on these results, in the early period of COVID-19 vaccine administration in the country (early 2021), before any governmental allowance and political intervention, we found that the socio-demographic and socio-cultural characteristics of the population were significant factors contributing to vaccination acceptance. Therefore, policymakers should support long-term safety studies of the vaccine, conduct educational programs giving high-priority to the populations' health, and tailor vaccination hesitancy reduction techniques to local communities.

Antimicrobial Resistance, Virulence Factor-Encoding Genes, and Biofilm-Forming Ability of Community-Associated Uropathogenic Escherichia coli in Western Saudi Arabia.

To explore the prevalence of multidrug-resistant community-associated uropathogenic Escherichia coli (UPEC) and their virulence factors in Western Saudi Arabia. A total of 1,000 urine samples were examined for the presence of E. coli by selective plating on MacConkey, CLED, and sheep blood agar. Antimicrobial susceptibility patterns were determined using Vitek® 2 Compact (MIC) and the disc diffusion method with Mueller-Hinton agar. Genes encoding virulence factors (kpsMTII, traT, sat, csgA, vat, and iutA) were detected by PCR. The overall prevalence of UTI-associated E. coli was low, and a higher prevalence was detected in samples of female origin. Many of the isolates exhibited resistance to norfloxacin, and 60% of the isolates showed resistance to ampicillin. No resistance to imipenem, meropenem, or ertapenem was detected. In general, half of the isolates showed multiple resistance patterns. UPEC exhibited a weak ability to form biofilms, where no correlation was observed between multidrug resistance and biofilm-forming ability. All uropathogenic E. coli isolates carried the kpsMTII, iutA, traT, and csgA genes, whereas the low number of the isolates harbored the sat and vat genes. The diversity of virulence factors harbored by community-associated UPEC may render them more virulent and further explain the recurrence/relapse cases among community-associated UITs. To the best of our knowledge, this study constitutes the first exploration of virulence, biofilm-forming ability, and its association with multidrug resistance among UPEC isolates in Saudi Arabia. Further investigations are needed to elucidate the epidemiology of community-associated UPEC in Saudi Arabia.

Dose optimization of ß-lactams antibiotics in pediatrics and adults: A systematic review.

Background: ß-lactams remain the cornerstone of the empirical therapy to treat various bacterial infections. This systematic review aimed to analyze the data describing the dosing regimen of ß-lactams. Methods: Systematic scientific and grey literature was performed in accordance with Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The studies were retrieved and screened on the basis of pre-defined exclusion and inclusion criteria. The cohort studies, randomized controlled trials (RCT) and case reports that reported the dosing schedule of ß-lactams are included in this study. Results: A total of 52 studies met the inclusion criteria, of which 40 were cohort studies, 2 were case reports and 10 were RCTs. The majority of the studies (34/52) studied the pharmacokinetic (PK) parameters of a drug. A total of 20 studies proposed dosing schedule in pediatrics while 32 studies proposed dosing regimen among adults. Piperacillin (12/52) and Meropenem (11/52) were the most commonly used ß-lactams used in hospitalized patients. As per available evidence, continuous infusion is considered as the most appropriate mode of administration to optimize the safety and efficacy of the treatment and improve the clinical outcomes. Conclusion: Appropriate antibiotic therapy is challenging due to pathophysiological changes among different age groups. The optimization of pharmacokinetic/pharmacodynamic parameters is useful to support alternative dosing regimens such as an increase in dosing interval, continuous infusion, and increased bolus doses.

A Systematic Review on Clinical Safety and Efficacy of Vancomycin Loading Dose in Critically Ill Patients.

BACKGROUND: The clinical significance of utilizing a vancomycin loading dose in critically ill patients remains unclear. OBJECTIVE: The main aim of this systematic review is to evaluate the clinical safety and efficacy of the vancomycin loading dose in critically ill patients. METHODS: We performed a systematic review using PRISMA guidelines. PubMed, the Web of Science, MEDLINE, Scopus, Google Scholar, the Saudi Digital Library and other databases were searched. Studies that reported clinical outcomes among patients receiving the vancomycin LD were considered eligible. Data for this study were collected using PubMed, the Web of Science, MEDLINE, Scopus, Google Scholar and the Saudi Digital Library using the following terms: "vancomycin", "safety", "efficacy" and "loading dose" combined with the Boolean operator "AND" or "OR". RESULTS: A total of 17 articles, including 2 RCTs, 11 retrospective cohorts and 4 other studies, met the inclusion/exclusion criteria out of a total 1189 studies. Patients had different clinical characteristics representing a heterogenous group, including patients in critical condition, with renal impairment, sepsis, MRSA infection and hospitalized patients for hemodialysis or in the emergency department. CONCLUSIONS: The study shows that the target therapeutic level is achieved more easily among patients receiving a weight-based LD as compared to patients received the usual dose without an increased risk of new-onset adverse drug reactions.

Preventive Measures and Management of Catheter-Associated Urinary Tract Infection in Adult Intensive Care Units in Saudi Arabia.

Catheter-associated Urinary Tract Infection (CAUTI) has been studied worldwide as part of device-related healthcare infection. CAUTI is one of the most commonly reported infections in the literature, which occurs during clinical practice in Intensive Care Units (ICUs) and non-ICU departments. Many studies have covered the CAUTI rate in Saudi Arabia mainly in the ICU covering single or multiple hospitals as surveillance for device-related infections in the ICU. Few studies have conducted an interventional approach that examined the implementation of infection control protocols and then compared them to international practice as a standard. This review aims to explore the literature to provide insight into the infection control practices that have been reported in Saudi Arabia during the last two decades on the preventive measures and clinical consequences of CAUTIs. Very few studies have recorded the pattern of resistant microorganisms that burdens clinical practice in ICUs concerning CAUTIs. Only one study compared the type of catheter materials and discussed the effect of these materials on reducing CAUTIs. It is essential to cover catheter utilization and to understand how a sufficient infection control protocol with educational programs for healthcare personnel can transform practice, for the better, regarding CAUTI rates in Saudi hospitals. There is a demand for more interventional and epidemiological studies on the causes and factors affecting the rate of CAUTI in the area. Studies may help reduce the CAUTI incidence rate, which consequently reduces the costs and morbidity associated with this type of infection and other healthcare-related infections.

Dose Optimization of Colistin: A Systematic Review.

Colistin is considered a last treatment option for multi-drug and extensively resistant Gram-negative infections. We aimed to assess the available data on the dosing strategy of colistin. A systematic review was performed to identify all published studies on the dose optimization of colistin. Grey literature and electronic databases were searched. Data were collected in a specified form and the quality of the included articles was then assessed using the Newcastle-Ottawa scale for cohort studies, the Cochrane bias tool for randomized clinical trials (RCT), and the Joanna Briggs Institute (JBI) critical checklist for case reports. A total of 19 studies were included, of which 16 were cohort studies, one was a RCT, and two were case reports. A total of 18 studies proposed a dosing regimen for adults, while only one study proposed a dosing schedule for pediatric populations. As per the available evidence, a loading dose of 9 million international units (MIU) of colistin followed by a maintenance dose of 4.5 MIU every 12 h was considered the most appropriate dosing strategy to optimize the safety and efficacy of treatment and improve clinical outcomes. This review supports the administration of a loading dose followed by a maintenance dose of colistin in severe and life-threatening multi-drug Gram-negative bacterial infections.