[Impact of Staphylococcus aureus bacteremia in COVID-19 patients]. / Impacto de la bacteriemia por Staphylococcus aureus en pacientes con COVID-19.

OBJECTIVE: The disease caused by SARS-CoV-2 (COVID-19) has been a challenge for healthcare professionals since its appearance. Staphylococcus aureus has been described as one of the main pathogens causing bacterial infections in viral pandemics. However, co- infection with S. aureus causing bacteremia in patients with COVID-19 has yet to be well studied. METHODS: We performed a e study of S. aureus bacteremia (SAB) at Hospital Miguel Servet (Zaragoza) from March 2020 to February 2021. The clinical characteristics, mortality and risk factors of adults hospitalized patients with BSA associated COVID-19 compared to patients without COVID-19. RESULTS: A total of 95 patients with SAB were identified. 27.3% were positive for SARS-CoV-2. SAB represented 9.9% of bacteremia, being the second agent in frequency after E. coli. Nosocomial bacteremia was more frequent in the group of COVID-19 patients. The most frequent source of BSA in these patients was the respiratory source (26.9% vs 0%; P<0.001) followed by the skin (15.5% vs 15.9%; P=1). The development of sepsis was more frequent in COVID-19 patients (61,5% vs 7,8%; P=0,336) and among them, who received dexamethasone at doses > 6 mg/day (62.5% vs. 37.5%, P<0.05). CONCLUSIONS: Our data suggest that BSA has a negative impact on the evolution of patients with COVID-19. However, further and preferably prospective studies are required to obtain solid data on the impact of BSA on coronavirus patients.

Multidrug-Resistant Kocuria rosea and Methicillin-Resistant Staphylococcus aureus Co-Infection in a Nigerian Patient with COVID-19: A Case Report.

BACKGROUND Bacterial Infections, especially, of the respiratory system, have been reported as one of the medical concerns in patients with the Coronavirus Disease-2019 (COVID-19), particularly those with multiple co-morbidities. We present a case of a diabetic patient with co-infection of multi-drug-resistant Kocuria rosea and methicillin-resistant Staphylococcus aureus (MRSA) who contracted COVID-19. CASE REPORT A 72-year-old man with diabetes presented with symptoms including cough, chest pain, urinary incontinence, respiratory distress, sore throat, fever, diarrhea, loss of taste, and anosmia and was confirmed to have COVID-19. At admission, he was also found to have sepsis. MRSA was isolated in conjunction with another organism, resembling coagulase-negative Staphylococcus, which was misidentified using commercial biochemical testing systems. The strain was finally confirmed to be Kocuria rosea by 16S rRNA gene sequencing. Both strains were highly resistant to multiple classes of antibiotics, but the Kocuria rosea was resistant to all the cephalosporins, fluoroquinolones, and macrolides tested. The use of ceftriaxone and ciprofloxacin did not improve his condition, which ultimately led to his death. CONCLUSIONS This case report shows that the presence of multi-drug-resistant bacteria infections can be fatal in patients with COVID-19, especially in patients with other co-morbidities like diabetes. This case report also shows that biochemical testing may be inadequate in identifying emerging bacterial infections and there is a need to include proper bacterial screening and treatment in the management of COVID-19, especially in patients with other co-morbidities and with indwelling devices.

Antimicrobial resistance prevalence of Escherichia coli and Staphylococcus aureus amongst bacteremic patients in Africa: a systematic review.

OBJECTIVES: Antimicrobial resistance (AMR) is a global concern among infectious diseases. Bloodstream infections can potentially become life-threatening if they become untreatable with conventional antimicrobials. This review aims to provide an understanding of the AMR prevalence and trends of common bacteremic pathogens, namely Escherichia coli and Staphylococcus aureus in the World Health Organization (WHO) Africa region. METHODS: PubMed and Google Scholar were searched using relevant keywords for published human studies (excluding case reports and reviews) reporting bacteremic AMR data on the pathogens of interest between 2008 and 2019. Two reviewers independently screened the articles against a pre-defined eligibility criterion. Data extraction and analysis were achieved with different platforms: Covidence, Excel, R version 3.6.3, and QGIS v3.4.5. The pooled prevalence, 95% confidence intervals, and I2 index (a measure of heterogeneity) were calculated for the various pathogen-antibiotic combinations. RESULTS: Five hundred sixty-two papers were retrieved, with 27 papers included in the final analysis. Only 23.4% (11/47) of member states of the WHO African region had reports on AMR in bacteremia. The Clinical and Laboratory Standards Institute (CLSI) (78.5%) was the most common standard used in the region. For E. coli, the pooled resistance was: cefotaxime (42%), imipenem (4%), meropenem (0%), and colistin (0%). For S. aureus, the calculated pooled resistance was cloxacillin (34%), oxacillin (12%), and vancomycin (0%). There was a high degree of variation across studies (I2 > 90%). CONCLUSION: The pooled resistance rates indicate a concerning degree of methicillin-resistant and Extended Spectrum-ß-lactamase-producing pathogens. The paucity of AMR data also presents challenges for a comprehensive understanding of the situation in the region. Continent-wide and standardized surveillance efforts therefore need strengthening.

Evaluating Methicillin-Resistant Staphylococcus aureus Polymerase Chain Reaction Nasal Screening as a Tool for Antimicrobial Stewardship.

INTRODUCTION: Initiation of broad-spectrum empiric antibiotics is common when infection is suspected in hospitalized adults. The benefits of early utilization of effective antibiotics are well documented. However, the negative effects of inappropriate antibiotic use have led to antimicrobial stewardship mandates. Recent data demonstrate the utility of methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) nasal screening to steward anti-MRSA empiric antibiotics in pneumonia. We hypothesize that MRSA PCR nasal swabs would also be effective to rule out other MRSA infection to effectively limit unnecessary antibiotics for any infectious source. METHODS: We performed a single-center retrospective chart review of all adult patient encounters from October 2019-July 2021 with MRSA PCR nasal testing. We then reviewed all charts to evaluate for the presence of infections based on source cultures results, as the gold standard. Sensitivity, specificity, negative predictive value, and positive predictive value were calculated from 2 × 2 contingency tables. RESULTS: Among all patients with MRSA nasal screening, 1189 patients had any infection. Prevalence of MRSA nasal carriage among patients screened was 12%. Prevalence of MRSA infection among all infections was 7.5%. MRSA nasal swabs demonstrated a negative predictive value of 100% for MRSA urinary tract infection, 97.9% for MRSA bacteremia, 97.8% for MRSA pneumonia, 92.1% for MRSA wound infection, and 96.6% for other MRSA infections. Overall, MRSA PCR nasal swabs had a sensitivity of 68.5%, specificity of 90.1%, positive predictive value of 23.7%, and negative predictive value of 98.5% for any infections. CONCLUSIONS: MRSA PCR nasal swabs have a high negative predictive value for all infections. Our data support the use of MRSA PCR nasal swabs to rule out MRSA infection and thereby allow early de-escalation of MRSA coverage in hospitalized patients requiring empiric antibiotics. Implementation of MRSA screening could decrease antibiotic-associated morbidity, resistance, and costs. More studies should be conducted to validate these results and support these findings.

Skin and soft tissue infections in the elderly.

PURPOSE OF REVIEW: To highlight the peculiarity of skin and soft tissue infections (SSTIs) in elderly patients and to provide useful elements for their optimal management. RECENT FINDINGS: In the COVID-19 era, early discharge from the hospital and implementation of outpatient management is of key importance. SUMMARY: Elderly patients are at high risk of SSTIs due to several factors, including presence of multiple comorbidities and skin factors predisposing to infections. Clinical presentation may be atypical and some signs of severity, such as fever and increase in C-reactive protein, may be absent or aspecific in this patients population. An appropriate diagnosis of SSTIs in the elderly is crucial to avoid antibiotic overtreatment. Further studies should explore factors associated with bacterial superinfections in patients with pressure ulcers or lower limb erythema. Since several risk factors for methicillin-resistant Staphylococcus aureus (MRSA) may coexist in elderly patients, these subjects should be carefully screened for MRSA risk factors and those with high risk of resistant etiology should receive early antibiotic therapy active against MRSA. Physicians should aim to several objectives, including clinical cure, patient safety, early discharge and return to community. SSTIs in the elderly may be managed using long-acting antibiotics, but clinical follow-up is needed.

Tetrahedral Framework Nucleic Acids: A Novel Strategy for Antibiotic Treating Drug-Resistant Infections.

Antibiotic multiresistance (AMR) has emerged as a major threat to human health as millions of people die from AMR-related problems every year. As has been witnessed during the global COVID-19 pandemic, the significantly increased demand for antibiotics has aggravated the issue of AMR. Therefore, there is an urgent need to find ways to alleviate it. Tetrahedral framework nucleic acids (tFNAs) are novel nanomaterials that are often used as drug delivery platforms because of their structural diversity. This study formed a tFNAs-antibiotic compound (TAC) which has a strong growth inhibitory effect on Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA) in vitro owing to the increased absorption of antibiotics by bacteria and improved drug movement across cell membranes. We established a mouse model of systemic peritonitis and local wound infections. The TAC exhibited good biosafety and improved the survival rate of severely infected mice, promoting the healing of local infections. In addition to the better transport of antibiotics to the target, the TAC may also enhance immunity by regulating the differentiation of M1 and M2 macrophages, providing a new option for the treatment of infections.

Waterhouse-Friderichsen Syndrome with Bilateral Adrenal Hemorrhage Associated with Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia in an Adult Patient with History of Intravenous Drug Use.

BACKGROUND Waterhouse-Friderichsen syndrome, also known as acute adrenal insufficiency due to adrenal gland hemorrhage, is an uncommon and frequently fatal condition classically presenting with fever, shock, rash, and coagulopathy. Although most often associated with Meningococcemia, many other etiologies have been implicated, including reports of Staphylococcus aureus infection on autopsy examinations. This report details an adult intravenous drug user with adrenal hemorrhage associated with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. CASE REPORT A 58-year-old man with a history of intravenous drug use presented to the hospital with weakness. Vitals were initially normal and exam findings were notable for decreased right-sided motor strength. Magnetic resonance imaging (MRI) revealed a cervical epidural abscess with spinal cord compression. Despite initiation of broad-spectrum antibiotics and intravenous fluids, the patient progressed to shock, requiring vasopressor administration, and his blood cultures later grew MRSA. Further imaging of the abdomen/pelvis was completed, revealing bilateral adrenal hemorrhage. Random cortisol at that time was 5.6 µg/dL, confirming a diagnosis of critical illness-related corticosteroid insufficiency in addition to likely septic and spinal shock. The patient was initiated on hydrocortisone with improvement in his hypotension. He was transitioned to prednisone and fludrocortisone in addition to 8 weeks of antibiotics after achieving clinical stability. CONCLUSIONS This report brings to attention the risk of adrenal hemorrhage and acute adrenal insufficiency as a sequela of the relatively common illness of Staphylococcus aureus bacteremia. As symptoms of adrenal insufficiency can overlap with septic shock related to the primary condition, this diagnosis requires a high index of suspicion in the critically ill patient.

Antibiotic combinations reduce Staphylococcus aureus clearance.

The spread of antibiotic resistance is attracting increased attention to combination-based treatments. Although drug combinations have been studied extensively for their effects on bacterial growth1-11, much less is known about their effects on bacterial long-term clearance, especially at cidal, clinically relevant concentrations12-14. Here, using en masse microplating and automated image analysis, we systematically quantify Staphylococcus aureus survival during prolonged exposure to pairwise and higher-order cidal drug combinations. By quantifying growth inhibition, early killing and longer-term population clearance by all pairs of 14 antibiotics, we find that clearance interactions are qualitatively different, often showing reciprocal suppression whereby the efficacy of the drug mixture is weaker than any of the individual drugs alone. Furthermore, in contrast to growth inhibition6-10 and early killing, clearance efficacy decreases rather than increases as more drugs are added. However, specific drugs targeting non-growing persisters15-17 circumvent these suppressive effects. Competition experiments show that reciprocal suppressive drug combinations select against resistance to any of the individual drugs, even counteracting methicillin-resistant Staphylococcus aureus both in vitro and in a Galleria mellonella larva model. As a consequence, adding a ß-lactamase inhibitor that is commonly used to potentiate treatment against ß-lactam-resistant strains can reduce rather than increase treatment efficacy. Together, these results underscore the importance of systematic mapping the long-term clearance efficacy of drug combinations for designing more-effective, resistance-proof multidrug regimes.

Clinical utility of negative methicillin-resistant Staphylococcus aureus (MRSA) nasal surveillance swabs in skin and skin structure infections.

BACKGROUND: Negative methicillin-resistant Staphylococcus aureus (MRSA) nasal swabs have a high negative predictive value of approximately 99% in respiratory infections. There is, however, a lack of data evaluating its use beyond respiratory infections. METHODS: We conducted a retrospective analysis to determine the clinical utility of MRSA swabs for identifying MRSA-associated skin and skin structure infections (SSSIs) and the potential effects on antimicrobial stewardship efforts. Baseline characteristics, culture data, and antibiotic data were collected to determine the difference in duration of vancomycin therapy. Positive predictive value, negative predictive value, sensitivity, and specificity were secondary outcomes. RESULTS: A total of 473 patients were included, of which 156 patients had a positive MRSA nasal swab and 317 patients had a negative swab. The median duration of vancomycin was 4 days in the positive group and 3 days in the negative group (P = .01). The positive predictive value and negative predictive value were 22.4% and 97.5%. The sensitivity and specificity were 81.4% and 71.9%. CONCLUSION: Patients with a negative MRSA nasal swab received approximately 1 day less of vancomycin, which represented a decrease in drug administered. The negative predictive value for SSSIs is promising, showing potential for the role of MRSA nasal swabs in de-escalating therapy.

Update on Staphylococcus aureus bacteraemia.

PURPOSE OF REVIEW: To review recently published evidence relevant to Staphylococcus aureus bacteremia (SAB). RECENT FINDINGS: Staphylococcus aureus is the most common pathogen causing co-infections and superinfections in patients with COVID-19. Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia ratios have sharply risen during the pandemic. SAB mortality is 18% at 1 month and 27% at 3 months but has gradually decreased over the last 30 years. Recurrences and reinfections are common (9%). Standardised items to define complicated SAB, and a new cut-off defining persisting bacteremia after 2 days with positive blood cultures have been proposed. Multiple antibiotic combinations have been trialled including vancomycin or daptomycin with ß-lactams, fosfomycin, or clindamycin, without significant results. In the recently published guidelines, vancomycin remains the first line of treatment for MRSA bacteremia. For the management of methicillin-susceptible Staphylococcus aureus , cefazolin less frequently causes acute kidney injury than flucloxacillin, and when susceptibility is demonstrated, de-escalation to penicillin G is suggested. SUMMARY: Our review confirms that Staphylococcus aureus represents a special aetiology among all causes of bloodstream infections. Pending results of platform and larger trials, its distinct epidemiology and determinants mandate careful integration of clinical variables and best available evidence to optimize patient outcomes.

Secondary bacterial infections of the respiratory tract in COVID-19 patients.

INTRODUCTION: Secondary Bacterial Infections (SBIs) of the respiratory system are one of the biggest medical concerns in patients undergoing hospitalization with a diagnosis of COVID-19. This study aims to provide relevant data for the initiation of appropriate empirical treatment after examining the etiology and antimicrobial resistance of SBIs in COVID-19 patients under care in the Intensive Care Units (ICUs) in the largest pandemic hospital of our country. METHODOLOGY: Between March 16, 2020 and December 31, 2021, 56,993 COVID patients were hospitalized, of which 7684 were admitted to ICUs. A total of 1513 patients diagnosed with SBIs have been included in this study. During the course of the study, demographic data, clinical course, etiology and antimicrobial resistance data of all patients were collected. RESULTS: The most common causative agents of SBIs were inferred as Acinetobacter baumanii (35.1%), Staphylococcus aureus (15.2%), Klebsiella pneumoniae (12.3%) and Pseudomonas aeruginosa (10.4%). The isolation rates of carbapenem-resistant and colistin-resistant A. baumannii, K. pneumoniae and P. aeruginosa were 83.7%; 42.7%, 79.2%, and 5.6%, 42.7%, 1.7%, respectively. Acinetobacter pittii clustering was seen in one of the ICUs in the hospital. Multidrug resistant 92 (5.4%) Corynebacterium striatum isolates were also found as a causative agent with increasing frequency during the study period. CONCLUSIONS: SBI of the respiratory system is one of the major complications in patients hospitalized with COVID-19. The antimicrobial resistance rates of the isolated bacteria are generally high, which indicates that more accurate use of antibacterial agents is necessary for SBIs in patients hospitalized with COVID-19 diagnosis.

Epidemiology and antimicrobial susceptibility of Staphylococcus aureus in children in a tertiary care pediatric hospital in Milan, Italy, 2017-2021.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is highly prevalent worldwide and can cause severe diseases. MRSA is associated with other antibiotic resistance. COVID-19 pandemic increased antimicrobial resistance in adult patients. Only a few data report the antimicrobial susceptibility of S. aureus in the Italian pediatric population, before and during the COVID-19 pandemic. METHODS: We included all the S. aureus positive samples with an available antibiogram isolated from pediatric patients (< 18 years old) in a tertiary care hospital in Milan, Italy, from January 2017 to December 2021. We collected data on demographics, antimicrobial susceptibility, and clinical history. We compared methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA strains. We calculated the frequency of isolation by year. The incidence of isolates during 2020 was compared with the average year isolation frequency using the univariate Poisson test. We compared the proportion of MRSA isolates during 2020 to the average proportion of other years with the Chi-squared test. RESULTS: Our dataset included a total of 255 S. aureus isolated from 226 patients, 120 (53%) males, and 106 (47%) females, with a median age of 3.4 years (IQR 0.8 - 10.5). The mean isolation frequency per year was 51. We observed a significant decrease of isolations during 2020 (p = 0.02), but after adjusting for the total number of hospitalization per year there was no evidence that the incidence changed. Seventy-six (30%) S. aureus were MRSA. Twenty (26%) MRSA vs 23 (13%) MSSA (p = 0.02) were hospital-acquired. MRSA strains showed higher resistance to cotrimoxazole, clindamycin, macrolides, levofloxacin, gentamicin, and tetracyclin than MSSA strains. None of MRSA were resistant to linezolid and vancomycin, one was resistant to daptomycin. The proportion of MRSA did not change during the COVID-19 pandemic. The overall clindamycin resistance was high (17%). Recent antibiotic therapy was related to MRSA infection. CONCLUSION: The proportion of MRSA did not change during the COVID-19 pandemic and remained high. Clindamycin should not be used as an empirical MRSA treatment due to its high resistance.

Decreased quality of care for Staphylococcus aureus bacteremia during the COVID-19 pandemic.

OBJECTIVES: Staphylococcus aureus bacteremia (SAB) is one of the most frequent bloodstream infections. High mortality of SAB can be significantly reduced by regular infectious disease (ID) consultations and appropriate clinical management. Because the pandemic of coronavirus disease 2019 (COVID-19) has had a negative impact on hospital ID service, it can be assumed that it has also led to decreased quality of care for SAB patients. METHODS: This study enrolled all (n = 68) patients with proven SAB who were hospitalized in Military University Hospital, Prague, in 2019 and 2020 and the quality of care indicators for SAB patients were compared. RESULTS: A total of 33 and 35 patients with SAB were hospitalized in our hospital in 2019 and 2020, respectively. The significant difference between the pandemic year 2020 and year 2019 was in ID consultations performed (74% vs. 100%; p = 0.002) and fulfilment of all quality of care indicators (66% vs. 93%; p = 0.012). Next, higher in-hospital mortality was observed in 2020 than in 2019 (6% vs. 23%; p = 0.085). There was no significant difference in the percentages of patients with performed echocardiographic examinations (66% vs. 83%; p = 0.156) and collected follow-up blood cultures (85% vs. 94%; p = 0.428). In addition, there was no difference between the two years in the adequate antibiotic therapy, sources, and bacterial origin of SAB. CONCLUSIONS: The quality of care of SAB patients significantly decreased during the COVID-19 pandemic in our institution.

Antibacterial, Antibiofilm, and Antiviral Farnesol-Containing Nanoparticles Prevent Staphylococcus aureus from Drug Resistance Development.

Multidrug antimicrobial resistance is a constantly growing health care issue associated with increased mortality and morbidity, and huge financial burden. Bacteria frequently form biofilm communities responsible for numerous persistent infections resistant to conventional antibiotics. Herein, novel nanoparticles (NPs) loaded with the natural bactericide farnesol (FSL NPs) are generated using high-intensity ultrasound. The nanoformulation of farnesol improved its antibacterial properties and demonstrated complete eradication of Staphylococcus aureus within less than 3 h, without inducing resistance development, and was able to 100% inhibit the establishment of a drug-resistant S. aureus biofilm. These antibiotic-free nano-antimicrobials also reduced the mature biofilm at a very low concentration of the active agent. In addition to the outstanding antibacterial properties, the engineered nano-entities demonstrated strong antiviral properties and inhibited the spike proteins of SARS-CoV-2 by up to 83%. The novel FSL NPs did not cause skin tissue irritation and did not induce the secretion of anti-inflammatory cytokines in a 3D skin tissue model. These results support the potential of these bio-based nano-actives to replace the existing antibiotics and they may be used for the development of topical pharmaceutic products for controlling microbial skin infections, without inducing resistance development.

Legionella pneumophila and Staphylococcus aureus co-infections in a patient with SARS-CoV-2.

A man fully mRNA-vaccinated against COVID-19 presented to our hospital with an acute febrile illness, respiratory symptoms and a positive test for SARS-CoV-2. He was later found early into hospitalisation to have two morbid bacterial co-infections: Legionella pneumophila serogroup 1 and methicillin-resistant Staphylococcus aureus (MRSA). Although this patient was initially admitted for COVID-19 management, his initial presentation was remarkable for lobar pneumonia, hyponatraemia and rhabdomyolysis more compatible with Legionnaire's disease than severe COVID-19. On discovery of MRSA pneumonia as a second bacterial infection, immunosuppressive COVID-19 therapies were discontinued and targeted antibiotics towards both bacterial co-infections were initiated. The patient's successful recovery highlighted the need to have high suspicion for bacterial co-infections in patients presenting with community-acquired pneumonia and a positive SARS-CoV-2 test, as patients with serious bacterial co-infections may have worse outcomes with use of immunosuppressive COVID-19 therapies.

Native aortic valve Staphylococcus warneri endocarditis after COVID-19 infection: a case report and a review of literature.

We report a case of Staphylococcus warneri native valve endocarditis in an immunocompetent healthy adult, without known risk factors for infective endocarditis, two months following COVID-19 infection, who recovered with conservative treatment. Additionally, we reviewed previous cases of native valve endocarditis caused by Staphylococcus warneri and summarized the main clinical implications.