Identification of Risk Factors for Nasal Colonization of Methicillin-resistant Staphylococcus aureus and Vancomycin-resistant Staphylococcus aureus in Health Workers at a Tertiary Hospital, Indonesia

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant S. aureus (VRSA) frequently cause nosocomial infections yearly. During the COVID-19 pandemic, the potential for excessive use of antibiotics is a global threat to the increasing incidence of multiresistant bacteria. AIM: This study aimed to determine MRSA and VRSA colonization and identify factors associated with the risk of MRSA and VRSA nasal colonization in health workers at Dr. Soemarno Sosroatmodjo General Hospital, Kuala Kapuas, as one of the type C hospitals in Indonesia. METHOD(S): This cross-sectional analytic study at Dr. Soemarno Sosroatmodjo General Hospital, a tertiary hospital in Indonesia. A 128 health workers' subjects had undergone nasal swab screening for MRSA and VRSA colonization examinations. Then, they were asked to complete a questionnaire concerning the risk factors of MRSA and VRSA infections. RESULT(S): Nasal swab results obtained as many as 30 (23.5%) MRSA positive subjects and 6 (4.7%) subjects with positive VRSA. The most common risk factors that led to MRSA colonization included a history of positive MRSA in the previous hospital (60%), a history of ear, nose, and throat infection (41.7%), and did not do hand rub/handwash (36.7%). In comparison, the most risk factors for VRSA colonization were having pigs farm at home (33.3%), a history of positive MRSA in the previous hospital (20%), and a history of hospitalization in the past 6-12 months (16.7%). The results of multivariate analysis showed the most powerful and statistically significant risk factors in influencing nasal MRSA colonization were a history of positive MRSA in the previous hospital (OR 13.69, 95% confidence intervals [CI]: 1.34-140.25, p = 0.028) and did not do hand rub/handwash (OR 2.95, 95% CI: 1.167-7.49, p = 0.023). Meanwhile, marital status (OR 0.160, 95% CI: 0.02-1.06), p = 0.058) and home care service (OR 6.10, 95% CI: 0.79-46.96, p = 0.082) were the strongest risk factors for nasal colonization of VRSA but not statistically significant. CONCLUSION(S): As many as, 23.5% and 4.7% of healthcare workers' subjects were found with nasal colonization of MRSA and VRSA, respectively. Accordingly, strict policies are needed to minimize the transmission of these organisms from the hospital setting to the community.Copyright © 2023 Siti Nur Rohmah, Rizka Humardewayanti Asdie, Ida Yosopa, Daya Daryadijaya.

Knowledge of African Traditional Medicine System: Immunomodulation

African traditional medicine is one of the oldest forms of health-care system in the continent that has continued to be relevant. It is usually holistic, treating mind and body, and includes aromatherapy, bone setting, circumcision, herbs, homeopathy massaging, spiritual therapies, maternity care, psychiatric care, music therapy, and many more. It is a very old and culturally informed method of health management that humans have used against diseases that have threatened existence. More than 60,000 of the world's higher plant species can be found in sub-Saharan Africa and the Indian Ocean Islands. These are about one-fourth of the global total and less than the 8% of the medicinal plants sold internationally from Africa. This scarcity could be due to lack of data on the traditional uses of many African plants as the knowledge is transferred orally by storytellers and traditional healers though in recent times, there are some information in print. Immunomodulation is seen as an essential feature of immunotherapy whereby immune responses are provoked, heightened, decreased, or avoided. Immune responses have been observed to be either cellular co-receptor expression, class switching, cytokine secretion, histamine release, immunoglobulin secretion, lymphocyte expression, or phagocytosis. Immune system dysfunction is responsible for various diseases like allergies, asthmas, arthritis, cancers, and infectious diseases. So modulation of immune responses is required in controlling diseases. This is requisite nowadays because of the upsurge of infectious diseases like superbugs caused by Multi-Resistant Staphylococcus aureus (MRSA) and the coronavirus (COVID-19) plus other emerging diseases. The historical view of African Traditional Medicine (ATMs) will be discussed from the point of view of specific plants used for immunomodulation in the ATMs and their efficacies following the trend of use and development of herbal medicines from crude formulations to refined dosage forms and procedures over time. Most of the ATMs are prepared as tonics and bitters to heighten and keep up immune defenses. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.

Taking hospital pathogen surveillance to the next level.

High-throughput bacterial genomic sequencing and subsequent analyses can produce large volumes of high-quality data rapidly. Advances in sequencing technology, with commensurate developments in bioinformatics, have increased the speed and efficiency with which it is possible to apply genomics to outbreak analysis and broader public health surveillance. This approach has been focused on targeted pathogenic taxa, such as Mycobacteria, and diseases corresponding to different modes of transmission, including food-and-water-borne diseases (FWDs) and sexually transmitted infections (STIs). In addition, major healthcare-associated pathogens such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and carbapenemase-producing Klebsiella pneumoniae are the focus of research projects and initiatives to understand transmission dynamics and temporal trends on both local and global scales. Here, we discuss current and future public health priorities relating to genome-based surveillance of major healthcare-associated pathogens. We highlight the specific challenges for the surveillance of healthcare-associated infections (HAIs), and how recent technical advances might be deployed most effectively to mitigate the increasing public health burden they cause.

Impact of the COVID-19 pandemic on the incidence of surgical site infection after orthopaedic surgery: an interrupted time series analysis of the nationwide surveillance database in Japan.

BACKGROUND: During the COVID-19 pandemic, hygiene awareness was increased in communities and hospitals. However, there is controversy regarding whether such circumstances affected the incidence of surgical site infections (SSIs) in the orthopaedic surgical field. AIM: To examine the impact of the COVID-19 pandemic on the incidence of SSIs after orthopaedic surgery. METHODS: The medical records of patients having undergone orthopaedic surgery were extracted from the nationwide surveillance database in Japan. The primary outcomes were the monthly incidences of total SSIs, deep or organ/space SSIs, and SSIs due to meticillin-resistant Staphylococcus aureus (MRSA). Interrupted time series analysis was conducted between pre-pandemic (January 2017 to March 2020) and pandemic (April 2020 to June 2021) periods. RESULTS: A total of 309,341 operations were included. Interrupted time series analysis adjusted for seasonality showed no significant changes in the incidence of total SSIs (rate ratio 0.94 and 95% confidence interval 0.98-1.02), deep or organ/space SSIs (0.91, 0.72-1.15), or SSIs due to MRSA (1.07, 0.68-1.68) along with no remarkable slope changes in any parameter (1.00, 0.98-1.02; 1.00, 0.97-1.02; and 0.98, 0.93-1.03, respectively). CONCLUSIONS: Awareness and measures against the COVID-19 pandemic did not markedly influence the incidence of total SSIs, deep or organ/space SSIs, or SSIs due to MRSA following orthopaedic surgery in Japan.

The Hidden Cost of COVID-19: Focus on Antimicrobial Resistance in Bloodstream Infections.

Antibiotic resistance is one of the greatest growing public health threats and a worldwide priority. According to the WHO, drug-resistant diseases may cause 10 million deaths a year by 2050 and have a substantial impact on the global economy, driving up to 24 million people into poverty. The ongoing COVID-19 pandemic has exposed the fallacies and vulnerability of healthcare systems worldwide, displacing resources from existing programs and reducing funding for antimicrobial resistance (AMR) fighting efforts. Moreover, as already seen for other respiratory viruses, such as flu, COVID-19 is often associated with superinfections, prolonged hospital stays, and increased ICU admissions, further aggravating healthcare disruption. These events are accompanied by widespread antibiotic use, misuse, and inappropriate compliance with standard procedures with a potential long-term impact on AMR. Still, COVID-19-related measures such as increasing personal and environmental hygiene, social distancing, and decreasing hospital admissions could theoretically help the AMR cause. However, several reports have shown increased antimicrobial resistance during the COVID-19 pandemic. This narrative review focuses on this "twindemic", assessing the current knowledge of antimicrobial resistance in the COVID-19 era with a focus on bloodstream infections and provides insights into the lessons learned in the COVID-19 field that could be applied to antimicrobial stewardship initiatives.

Simulation of optimal dose regimens of photoactivated curcumin for antimicrobial resistance pneumonia in COVID-19 patients: A modeling approach.

Background: Secondary antimicrobial resistance bacterial (AMR) pneumonia could lead to an increase in mortality in COVID-19 patients, particularly of geriatric patients with underlying diseases. The comedication of current medicines for AMR pneumonia with corticosteroids may lead to suboptimal treatment or toxicities due to drug-drug interactions (DDIs). Objective: This study aimed to propose new promising dosage regimens of photoactivated curcumin when co-administered with corticosteroids for the treatment of antimicrobial resistance (AMR) pneumonia in COVID-19 patients. Methods: A whole-body physiologically-based pharmacokinetic (PBPK) with the simplified lung compartments model was built and verified following standard model verification (absolute average-folding error or AAFEs). The pharmacokinetic properties of photoactivated were assumed to be similar to curcumin due to minor changes in physiochemical properties of compound by photoactivation. The acceptable AAFEs values were within 2-fold. The verified model was used to simulate new regimens for different formulations of photoactivated curcumin. Results: The AAFEs was 1.12-fold. Original formulation (120 mg once-daily dose) or new intramuscular nano-formulation (100 mg with a release rate of 10/h given every 7 days) is suitable for outpatients with MRSA pneumonia to improve patient adherence. New intravenous formulation (2000 mg twice-daily doses) is for hospitalized patients with both MRSA and VRSA pneumonia. Conclusion: The PBPK models, in conjunction with MIC and applied physiological changes in COVID-19 patients, is a potential tool to predict optimal dosage regimens of photoactivated curcumin for the treatment of co-infected AMR pneumonia in COVID-19 patients. Each formulation is appropriate for different patient conditions and pathogens.

Microarray patches for managing infections at a global scale.

Since the first patent for micro array patches (MAPs) was filed in the 1970s, research on utilising MAPs as a drug delivery system has progressed significantly, evidenced by the transition from the simple 'poke and patch' of solid MAPs to the development of bio responsive systems such as hydrogel-forming and dissolving MAPs. In addition to the extensive research on MAPs for improving transdermal drug delivery, there is a growing interest in using these devices to manage infectious diseases. This is due to the minimally invasive nature of this drug delivery platform which enable patients to self-administer therapeutics without the aid of healthcare professionals. This review aims to provide a critical analysis on the potential utility of MAPs in managing infectious diseases which are still endemic at a global scale. The range of diseases covered in this review include tuberculosis, skin infections, malaria, methicillin-resistant Staphylococcus aureus infections and Covid-19. These diseases exert a considerable socioeconomic burden at a global scale with their impact magnified in low- and middle-income countries (LMICs). Due to the painless and minimally invasive nature of MAPs application, this technology also provides an efficient solution not only for the delivery of therapeutics but also for the administration of vaccine and prophylactic agents that could be used in preventing the spread and outbreak of emerging infections. Furthermore, the ability of MAPs to sample and collect dermal interstitial fluid that is rich in disease-related biomarkers could also open the avenue for MAPs to be utilised as a minimally invasive biosensor for the diagnosis of infectious diseases. The efficacy of MAPs along with the current limitations of such strategies to prevent and treat these infections will be discussed. Lastly, the clinical and translational hurdles associated with MAP technologies will also be critically discussed.

Studies on the Catechin Constituents of Bark of Cinnamomum sieboldii.

Screening for bioactivity related to anti-infective, anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-viral activity, led us to identify active compounds from a methanol extract of Litsea japonica (Thub.) Juss. and the hot water extract of bark of Cinnamomum sieboldii Meisn (also known as Karaki or Okinawa cinnamon). The two main components in these extracts were identified as the catechin trimers (+)-cinnamtannin B1 and pavetannin B5. Moreover, these extracts exhibited anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity. The structures of these catechin trimers were previously determined by chemical and spectroscopic methods. Pavetanin B5 has never been reported to be isolated as a pure form and has been obtained as a mixture with another component. Although other groups have reported the putative structure of pavetannin B5, preparation of the methylated derivative of pavetannin B5 in this study allowed us to obtain the pure form for the first time as the undecamethyl derivative and confirm its exact structure. Commercially available (+)-cinnamtannin B1 and aesculitannin B (C2'-epimer of cinnamtannin B1) both of which contained pavetannin B5 as a minor component, and C. sieboldii bark extract (approx. 5/2 mixture of (+)-cinnamtannin B1/pavetannin B5) were assessed for anti-SARS-CoV-2 activity. Both C. sieboldii bark extract and commercially available aesculitannin B showed viral growth inhibitory activity.

Surveillance Study on Bacterial Contamination Associated With Automated Teller Machines of Different Banks in Jazan Region

The environmental surfaces play an important role in the spread of pathogens and infectious diseases. Human are particularly susceptible to pick up microbes from environmental objects, especially from publicly and regularly used objects. The Automated teller machines (ATMs) are very likely to be the reservoir of different kinds of microorganisms, both pathogenic and non-pathogenic. In our study, we investigated the microbial contamination of multiple ATM machines in Jazan region. This is a descriptive cross-sectional study which was conducted between September to November, 2021. A sum of 42 sample were collected which yielded a total of 15 isolated bacterial species that was identified as follows: Bacillus spp. (73%), CoNS. (15%), Staphylococcus aureus (14%), Pseudomonas luteola (12.5%), Pantoea agglomerans (10%), Acinetobacter baumannii (7.5%), Escherichia coli (5%), Enterobacter cloacae (5%), and other 5 Gram negative species (total of 12.5%). Antibiotic susceptibility pattern of the isolates to commonly prescribed antibiotics showed that the highest resistant species are S. aureus (44%), CNS (48%) and E. coli (40%), while all the other bacteria showed varied degrees of resistance to the antibiotics tested. These results suggest that ATMs machines may play a role in transmission of drug resistant bacteria in Jazan, therefore, creating a public health risk. Intriguingly, our study comes after a large-scale and intense hygienic COVID-19 awareness programs. Hence, there is an urgent need to implement and improve hygienic practices and regulation when using such public machines.

Pneumocystis jirovecii and methicillin-resistant Staphylococcus aureus superinfection, a challenge in a post-COVID-19 scenario

We present a case of an 87-year-old nonsmoker female who recovered after infection by SARS-CoV-2 and was readmitted two weeks later due to respiratory sepsis. Radiological imaging showed a significant radiological worsening with extensive areas of bronchopneumonia and ground-glass opacities suggestive of organizing pneumonia. Empirical treatment with meropenem 1g/8h was started;however, clinical worsening persisted with tachypnea and desaturation requiring heated high-flow nasal cannula oxygen therapy, with poor response. Methicillin-resistant Staphylococcus aureus was isolated both in nasal screening swab and sputum, and RNA polymerase chain reaction in induced sputum was positive for P. jirovecii. Serum (1-3)-beta-D-glucan was normal, and blood cultures were sterile. Antibiotic therapy was adjusted with intravenous linezolid 600mg/12h and trimethoprim-sulfamethoxazole 320/1600mg/6h, plus methylprednisolone 40mg/day. Unfortunately, the patient had no response to optimized treatment and finally died. Clinicians should be aware of opportunistic and resistant microorganisms superinfections in relation to SARS-CoV-2 infection, even more, when corticosteroids are widely used.

Topical review on nano-vaccinology: Biochemical promises and key challenges.

Nanomaterials have wide-ranging biomedical applications in prevention, treatment and control of diseases. Nanoparticle based vaccines have proven prodigious prophylaxis of various infectious and non-infectious diseases of human and animal concern. Nano-vaccines outnumber the conventional vaccines by virtue of plasticity in physio-chemical properties and ease of administration. The efficacy of nano-based vaccines may be attributed to the improved antigen stability, minimum immuno-toxicity, sustained release, enhanced immunogenicity and the flexibility of physical features of nanoparticles. Based on these, the nano-based vaccines have potential to evoke both cellular and humoral immune responses. Targeted and highly specific immunological pathways required for solid and long lasting immunity may be achieved with specially engineered nano-vaccines. This review presents an insight into the prevention of infectious diseases (of bacterial, viral and parasitic origin) and non-infectious diseases (cancer, auto-immune diseases) using nano-vaccinology. Additionally, key challenges to the effective utilization of nano-vaccines from bench to clinical settings have been highlighted as research domains for future.

Considering the precautionary principle and its application to MRSA and SARS-CoV-2 as emerging novel pathogens of their time.

In the 1980s Contact Precautions were introduced as a precautionary measure to control the emerging threat of antimicrobial resistance in hospitals, particularly methicillin resistant Staphylococcus aureus (MRSA). Today, antimicrobial resistance remains a concerning global public health threat, and a focus for hospital patient safety priorities. In late 2019 a novel respiratory virus described as SARS-CoV-2, was reported. Just as MRSA had prompted control measures developed in the context of limited information and understanding of the pathogen, public health control measures against SARS-CoV-2 were promptly and strictly implemented. Whilst SARS-CoV-2 control measures were successful at containing the virus, numerous detrimental socio-economic and health impacts have led to a rebalancing of harms versus benefits and loosening of restrictions. Conversely, evidence collated over the past 50 years, suggests that Contact Precautions are not superior to well-applied standard infection prevention and control precautions in controlling MRSA acquisition in hospitals. Several harms associated with Contact Precautions, affecting patient safety, financial costs, and organisational culture, are described. However, rebalancing of hospital MRSA control policies has been slow to materialise. This commentary invites infection prevention and control policy makers to reflect and revise policies for the control of MRSA in hospitals so that harms do not outweigh benefits.

The Prevalence and Clinical Characteristics of Multidrug-resistant Hospital-acquired Staphylococcus aureus in Medina, Saudi Arabia

Hospital acquired-Staphylococcus aureus (HA-Staphylococcus aureus), particularly methicillin-resistant Staphylococcus aureus (MRSA), are an important source of nosocomial infections with high morbidity and mortality rates. Few reports showed that infections due to HA-Staphylococcus aureus in Saudi Arabia is increasing, particularly infections attributed to HA-MRSA. The study aimed to explore the prevalence and clinical characteristics of HA-Staphylococcus aureus for the first time in Medina, Saudi Arabia. A total of 1262 clinical samples of hospitalized patients were examined for the presence of Staphylococcus aureus through selective culturing on mannitol salt agar. Vitek Compact System and conventional methods were followed to confirm the isolates. Vitek Compact System tested the antimicrobial susceptibility of isolates whereas the standard PCR was employed to detect the genes encoding antimicrobial resistance (mecA and vanA) and virulence factors (tst, et, and LukS-PV). The overall HA-Staphylococcus aureus prevalence was low (6.58%, n = 1262) of which 84.34% (n = 83) were MRSA. Approximately, 57 samples of the 70 MRSA (81.5%) exhibited a multidrug-resistance (MDR) pattern. All the 83 HA-Staphylococcus aureus isolates were negative for the genes encoding toxic shock syndrome toxin, exfoliative toxin, and Panton-Valentine leukocidin. The study was conducted during the Covid-19 pandemic under partial lockdown, restricted hospitalization, and increased disinfection and infection control measures. Therefore, the low prevalence of HA-Staphylococcus aureus should be carefully interpreted and further multicenter investigations could reveal its true incidence in the city. The high prevalence of MDR HA-MRSA is alarming as it highlights inappropriate antibiotic prescriptions to counter staphylococcal infections. HA-Staphylococcus aureus investigated in this study might lack certain virulence factors. However, their MDR traits and invasive nature could worsen the situation if not properly handled. Copyright © 2023 The Author(s).

Post-COVID-19 Spondylodiscitis: A Case Study and Review of the Literature.

COVID-19 is currently a major health problem, leading to respiratory, cardiovascular and neurological complications, with additional morbidity and mortality. Spinal infections are rare, representing around 1% of all bone infections and comprising less than 2 per 10,000 of all hospitalizations in tertiary care centers. Spondylodiscitis is a complex disease, with challenging diagnosis and management. We report the case of a 45-year-old man, non-smoker hospitalized for severe COVID-19 disease with respiratory failure. Post-COVID-19, in the 8th week after discharge, he was diagnosed by magnetic resonance imaging with spondylodiscitis, but etiology was not confirmed by microbiological investigations. Antibiotics were used, considering the identification of MRSA from cultures of pleural fluid and nasal swab, but surgical intervention was not provided. Clinic, biologic and imagistic were improved, but rehabilitation and long term follow up are necessary. We concluded that spondylodiscitis with spinal abscess is a rare but severe complication post-COVID-19 disease, due to dysbalanced immune response related to the respiratory viral infection, endothelial lesions, hypercoagulation and bacterial superinfection.

COVID-19 and Cavitary Lesion in Lung.

The clinical manifestations of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are widespread, ranging from asymptomatic to critical illness with significant morbidity and mortality. It is widely known that individuals who have viral respiratory infections are more likely to develop bacterial infections. Throughout the pandemic, despite the fact that COVID-19 was thought to be the primary cause of millions of deaths, bacterial coinfections, superinfections, and other secondary complications played a significant role in the increased mortality rate. In our case, a 76-year-old male presented to the hospital complaining of shortness of air. Polymerase chain reaction (PCR) testing was positive for COVID-19 and cavitary lesions were discovered on imaging. Treatment was guided based on the results of bronchoscopy with bronchoalveolar lavage (BAL) cultures showing methicillin-resistant Staphylococcus aureus (MRSA) and Mycobacterium gordonae. However, the case was later complicated by the development of a pulmonary embolism after anticoagulants were held due to new onset hemoptysis. Our case highlights the importance of considering bacterial coinfection in cavitary lung lesions, appropriate antimicrobial stewardship, and close follow-up for full recovery in COVID-19 infections.

Changes in the Use of Antibiotics for Methicillin-Resistant Staphylococcus aureus Bloodstream Infections in Children: A 5-Year Retrospective, Single Center Study.

Monitoring antibiotic use in the pediatric population is a challenge, especially when determining a relationship between specific pathogens, infections, and antibiotic use. We retrospectively analyzed the consumption of anti-methicillin-resistant Staphylococcus aureus (MRSA) drugs from 2017 to 2021 at Istituto Giannina Gaslini by means of defined daily dose (DDD) adopted for adults by World Health Organization. We observed a statistically significant increase in the use of daptomycin and ceftaroline, combined with a decrease in the use of vancomycin. In the same period, we observed an increase in the proportion of bloodstream infections due to MRSA with vancomycin minimally inhibitory concentration (MIC mg/L) = 1, that represented the 100% of cases in 2021. This aspect was combined with the observation that in the 59% of cases, where vancomycin plasma concentrations were evaluated, it was not possible to achieve a ratio of the 24-h area under the concentration-time curve and MIC (AUC0-24/MIC) of vancomycin ≥ 400 mg/L. This study confirms that DDD can be used in pediatrics to monitor antibiotic consumption in relationship with infections epidemiology. Moreover, it describes the presence of vancomycin MIC creep for MRSA also in pediatrics and the difficulties in obtaining effective vancomycin plasma concentrations in children.

Incidence of bloodstream infections due to multidrug-resistant pathogens in ordinary wards and intensive care units before and during the COVID-19 pandemic: a real-life, retrospective observational study.

PURPOSE: SARS-COV-2 pandemic led to antibiotic overprescription and unprecedented stress on healthcare systems worldwide. Knowing the comparative incident risk of bloodstream infection due to multidrug-resistant pathogens in COVID ordinary wards and intensive care-units may give insights into the impact of COVID-19 on antimicrobial resistance. METHODS: Single-center observational data extracted from a computerized dataset were used to identify all patients who underwent blood cultures from January 1, 2018 to May 15, 2021. Pathogen-specific incidence rates were compared according to the time of admission, patient's COVID status and ward type. RESULTS: Among 14,884 patients for whom at least one blood culture was obtained, a total of 2534 were diagnosed with HA-BSI. Compared to both pre-pandemic and COVID-negative wards, HA-BSI due to S. aureus and Acinetobacter spp. (respectively 0.3 [95% CI 0.21-0.32] and 0.11 [0.08-0.16] new infections per 100 patient-days) showed significantly higher incidence rates, peaking in the COVID-ICU setting. Conversely, E. coli incident risk was 48% lower in COVID-positive vs COVID-negative settings (IRR 0.53 [0.34-0.77]). Among COVID + patients, 48% (n = 38/79) of S. aureus isolates were resistant to methicillin and 40% (n = 10/25) of K. pneumoniae isolates were resistant to carbapenems. CONCLUSIONS: The data presented here indicate that the spectrum of pathogens causing BSI in ordinary wards and intensive care units varied during the pandemic, with the greatest shift experienced by COVID-ICUs. Antimicrobial resistance of selected high-priority bacteria was high in COVID positive settings.

Success and failures in MRSA infection control during the COVID-19 pandemic.

Private sector facilities in the United States have experienced a resurgence of Methicillin-resistant Staphylococcus aureus (MRSA) hospital-onset infections during the COVID-19 pandemic, which eliminated all gains that were achieved over the last decade. The third quarter of 2021, the Standardized Infection Ratio for hospital onset MRSA bloodstream infections was 1.17, well above the baseline value of 1.0. In contrast, the Veterans Health Administration (VHA) has been able to maintain its mitigation efforts and low rates of MRSA hospital-onset infections through the second quarter of fiscal year 2022 (Mar. 31, 2022), the most recent available data. The difference may be explained not only by the VHA's use of uniform mitigating policies which rely on active surveillance and contact precautions, but also on the VAH's ability to maintain adequate staffing during the pandemic. Future research into MRSA mitigation is warranted and this data supports the need for healthcare system transformation.

Impact of COVID-19 pandemic on multidrug resistant gram positive and gram negative pathogens: A systematic review.

BACKGROUND: There is paucity of data describing the impact of COVID-19 pandemic on antimicrobial resistance. This review evaluated the changes in the rate of multidrug resistant gram negative and gram positive bacteria during the COVID-19 pandemic. METHODS: A search was conducted in PubMed, Science Direct, and Google Scholar databases to identify eligible studies. Studies that reported the impact of COVID-19 pandemic on carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Enterobacteriaceae (CRE), extended-spectrum beta-lactamase inhibitor (ESBL)-producing Enterobacteriaceae, vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Pseudomonas aeruginosa (CPE) were selected. Studies published in English language from the start of COVID-19 pandemic to July 2022 were considered for inclusion. RESULTS: Thirty eligible studies were selected and most of them were from Italy (n = 8), Turkey (n = 3) and Brazil (n = 3). The results indicated changes in the rate of multidrug resistant bacteria, and the changes varied between the studies. Most studies (54.5%) reported increase in MRSA infection/colonization during the pandemic, and the increase ranged from 4.6 to 170.6%. Five studies (55.6%) reported a 6.8-65.1% increase in VRE infection/colonization during the pandemic. A 2.4-58.2% decrease in ESBL E. coli and a 1.8-13.3% reduction in ESBL Klebsiella pneumoniae was observed during the pandemic. For CRAB, most studies (58.3%) reported 1.5-621.6% increase in infection/colonization during the pandemic. Overall, studies showed increase in the rate of CRE infection/colonization during the pandemic. There was a reduction in carbapenem-resistant E. coli during COVID-19 pandemic, and an increase in carbapenem-resistant K. pneumoniae. Most studies (55.6%) showed 10.4 - 40.9% reduction in the rate of CRPA infection during the pandemic. CONCLUSION: There is an increase in the rate of multidrug resistant gram positive and gram negative bacteria during the COVID-19 pandemic. However, the rate of ESBL-producing Enterobacteriaceae and CRPA has decrease during the pandemic. Both infection prevention and control strategies and antimicrobial stewardship should be strengthen to address the increasing rate of multidrug resistant gram positive and gram negative bacteria.

γ-Core Guided Antibiotic Design Based on Human Enteric Defensin 5.

An increase in the number of infections caused by resistant bacteria worldwide necessitates the development of alternatives to antibiotics. Human defensin (HD) 5 is an innate immune peptide with broad-spectrum antibacterial activity, but its complicated structure makes its preparation difficult. Herein, we truncated the HD5 structure by extracting the highly conserved γ-core motif. A structure-activity study showed that this motif was ineffective in killing bacteria in the absence of specific spatial conformation. Notably, after the introduction of two intramolecular disulfide bonds, its antibacterial activity was markedly improved. Glu and Ser residues were then replaced with Arg to create the derivative RC18, which exhibited stronger potency than HD5, particularly against methicillin-resistant S. aureus (MRSA). Mechanistically, RC18 bound to lipid A and lipoteichoic acid at higher affinities than HD5. Furthermore, RC18 was more efficient than HD5 in penetrating the bacterial membranes. Molecular dynamics simulation revealed that five Arg residues, Arg1, Arg7, Arg9, Arg15, and Arg18, mediated most of the polar interactions of RC18 with the phospholipid head groups during membrane penetration. In vivo experiments indicated that RC18 decreased MRSA colonization and dramatically improved the survival of infected mice, thus demonstrating that RC18 is a promising drug candidate to treat MRSA infections.