Infectious Diseases: What You May Have Missed in 2022.

In 2022, COVID-19 remained the infectious disease at the top of most internal medicine physicians' minds. However, it was not the only infectious disease that was the topic of clinically relevant research that year. This article highlights some important infectious disease evidence unrelated to COVID-19 that was published in 2022. The literature was screened for sound new evidence relevant to internal medicine specialists and subspecialists whose focus of practice is not infectious diseases. The publications highlighted relate to various organisms in different patient populations. One article provides insight into the role of Helicobacter pylori eradication in the treatment of functional dyspepsia. The descriptive epidemiology of bacterial (Staphylococcus aureus) and viral (mpox) infections are the focus of 2 other articles. Several articles address the management of resistant and difficult-to-treat infections: multidrug-resistant gram-negative infections, resistant HIV-1, rifampin-resistant tuberculosis, cryptococcal meningitis, and invasive fungal infection in the setting of neutropenia. Another article provides data on effective HIV preexposure prophylaxis in women, an understudied population. Finally, given the urgent need to reduce inappropriate use of antibiotics, an article on antibiotic stewardship for hospitalized patients with presumed sepsis in a non-intensive care unit setting is also included.

Effects of 5α-dihydrotestosterone on the modulation of monocyte/macrophage response to Staphylococcus aureus: an in vitro study.

BACKGROUND: Staphylococcus aureus (S. aureus) is a pathogen responsible for a wide range of clinical manifestations and potentially fatal conditions. There is a paucity of information on the influence of androgens in the immune response to S. aureus infection. In this study, we evaluated the influence of the hormone 5α-dihydrotestosterone (DHT) on mouse peritoneal macrophages (MPMs) and human peripheral blood monocytes (HPBMs) induced by S. aureus. METHODS: An in vitro model of MPMs from BALB/c sham males, orchiectomised (OQX) males, and females was used. Cells were inoculated with 10 µL of S. aureus, phage-type 80 or sterile saline (control) for 6 h. The MPMs of OQX males and females were pre-treated with 100 µL of 10-2 M DHT for 24 h before inoculation with S. aureus. The concentration of the cytokines TNF-α, IL-1α, IL-6, IL-8, and IL-10; total nitrites (NO-2); and hydrogen peroxide (H2O2) were measured in the supernatant of MPM cultures. In addition, the toll-like receptor 2 (TLR2) and nuclear factor kappa B (NF-kB) genes that are involved in immune responses were analysed. For the in vitro model of HPBMs, nine men and nine women of childbearing age were selected and HPBMs were isolated from samples of the volunteers' peripheral blood. In women, blood was collected during the periovulatory period. The HPBMs were inoculated with S. aureus for 6 h and the supernatant was collected for the analysis of cytokines TNF-α, IL-6, IL-12; and GM-CSF, NO-2, and H2O2. The HPBMs were then removed for the analysis of 84 genes involved in the host's response to bacterial infections by RT-PCR array. GraphPad was used for statistical analysis with a p value < 0.05. RESULTS: Our data demonstrated that MPMs from sham males inoculated with S. aureus displayed higher concentrations of inflammatory cytokines and lower concentrations of IL-10, NO-2, and H2O2 when compared with MPMs from OQX males and females. A similar result was observed in the HPBMs of men when compared with those of women. Previous treatment with DHT in women HPBMs increased the production of pro-inflammatory cytokines and decreased the levels of IL-10, NO-2, and H2O2. The analysis of gene expression showed that DHT increased the activity of the TLR2 and NF-kB pathways in both MPMs and HPBMs. CONCLUSIONS: We found that DHT acts as an inflammatory modulator in the monocyte/macrophage response induced by S. aureus and females exhibit a better immune defence response against this pathogen.

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.

Changes in the Protein Profile in Staphylococcal Strains from Patients Infected with the SARS-CoV-2 Virus.

Staphylococcus aureus strains are particularly often isolated from patients with SARS-CoV-2 infection. The aim of the current research was to determine whether the SARS-CoV-2 virus infection affects the protein profile of S. aureus. Bacteria were isolated from the forty swabs collected from the patients in the hospitals of the Pomeranian region. MALDI-TOF MS spectra were obtained using a Microflex LT instrument. Twenty-nine peaks were identified. The peak (2,430) is described here for the first time and was unique for the isolates from patients infected with the SARS-CoV-2 virus. These results support the hypothesis of bacterial adaptation to the conditions caused by viral infection.

Effect of Long-Term Use of Alcohol-Containing Handwashing Gels on the Biofilm-Forming Capacity of Staphylococcus epidermidis.

The spread of coronavirus disease 2019 (COVID-19) has promoted the use of hand sanitizers among the general population as recommended by health authorities. Alcohols, which are used in many hand sanitizers, have been shown to promotes the formation of biofilms by certain bacteria and to increase bacterial resistance to disinfection. We investigated the effect of continued use of alcohol-based gel hand sanitizer on biofilm formation by the Staphylococcus epidermidis resident strain isolated from the hands of health science students. Hand microbes were counted before and after handwashing, and the ability to produce biofilms was investigated. We found that 179 (84.8%) strains of S. epidermidis isolated from hands had the ability to form biofilm (biofilm-positive strains) in an alcohol-free culture medium. Furthermore, the presence of alcohol in the culture medium induced biofilm formation in 13 (40.6%) of the biofilm-negative strains and increased biofilm production in 111 (76.6%) strains, which were classified as low-grade biofilm-producing. Based on our findings, there is no clear evidence that the continued use of alcohol-based gels results in the selection of strains with the capacity to form biofilms. However, other disinfectant formulations that are more commonly used in clinical settings, such as alcohol-based hand-rub solutions, should be tested for their long-term effects.

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.

Staphylococcus aureus bacteremia in patients with SARS-CoV-2 infection.

OBJECTIVES: The aim was to compare the incidence of Staphylococcus aureus bacteremia in COVID-19 and non-COVID-19 adult patients during the pandemic period versus the previous two years. Also, we described the characteristics of both cohorts of patients in pandemic period to find differences. MATERIAL AND METHODS: Retrospective study in our tertiary-care centre reviewing S. aureus bacteremia episodes in COVID-19 and non-COVID-19 patients through clinical records and the Microbiology Department database. RESULTS: In 2018 and 2019, the incidence of S. aureus bacteremia episodes was 1.95 and 1.63 per 1000 admissions respectively. In the pandemic period, global incidence was 1.96 episodes per 1000 non-COVID-19 admissions and 10.59 episodes per 1000 COVID-19 admissions. A total of 241 bacteremia was registered during this pandemic period in 74 COVID-19 patients and in 167 non-COVID-19 patients. Methicillin resistance was detected in 32.4% and 13.8% of isolates from COVID-19 and non-COVID-19 patients respectively. In COVID-19 patients, mortality rates were significantly higher. CONCLUSIONS: We showed a significantly high rates of S. aureus bacteremia incidence in COVID-19 patients and higher methicillin resistance and 15-day mortality rates than in non-COVID-19 patients.

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.

Staphylococcus aureus Colonization in Healthy Children during the First Year of the Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic.

The early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic was temporally associated with a reduction in many childhood infections, although the impact on bacterial colonization is unknown. We longitudinally assessed Staphylococcusaureus colonization prior to and through the first year of the pandemic. We observed a decline in methicillin-resistant Staphylococcus aureus colonization associated with SARS-CoV-2 prevention mandates.

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.

Transient dynamics of infection transmission in a simulated intensive care unit.

Healthcare-associated infections (HAIs) remain a serious public health problem. In previous work, two models of an intensive care unit (ICU) showed that differing population structures had markedly different rates of Staphylococcus aureus (MRSA) transmission. One explanation for this difference is the models having differing long-term equilbrium dynamics, resulting from different basic reproductive numbers, R0. We find in this system however that this is not the case, and that both models had the same value for R0. Instead, short-term, transient dynamics, characterizing a series of small, self-limiting outbreaks caused by pathogen reintroduction were responsible for the differences. These results show the importance of these short-term factors for disease systems where reintroduction events are frequent, even if they are below the epidemic threshold. Further, we examine how subtle changes in how a hospital is organized-or how a model assumes a hospital is organized-in terms of the admission of new patients may impact transmission rates. This has implications for both novel pathogens introduced into ICUs, such as Ebola, MERS or COVID-19, as well as existing healthcare-associated infections such as carbapenem-resistant Enterobacteriaceae.

Risk factors for antimicrobial resistance among Staphylococcus isolated from pets living with a patient diagnosed with methicillin-resistant Staphylococcus aureus infection.

It has been suggested that pets play a critical role in the maintenance of methicillin-resistant (MR) and multidrug-resistant (MDR) Staphylococcus spp. in the household. We examined risk factors for carriage of antimicrobial-resistant coagulase-positive staphylococci, with particular attention to Staphylococcus aureus and Staphylococcus pseudintermedius isolated from pets living in households of people diagnosed with methicillin-resistant S. aureus (MRSA) skin or soft-tissue infection. We analyzed data collected cross-sectionally from a study conducted in 2012 that evaluated the transmission of MRSA and other staphylococci from humans, their pets and the environment (Pets and Environmental Transmission of Staphylococci [PETS] study). We used unadjusted and adjusted stratified logistic regression analyses with household-clustered standard errors to evaluate the association between demographic, healthcare-related, contact-related and environmental risk factors and MDR Staphylococcus spp. isolated from dogs and cats. Staphylococcal isolates obtained from dogs (n = 63) and cats (n = 47) were included in these analyses. The use of oral or injectable antimicrobials by the pets during the prior year was the main risk factor of interest. Based on our results, 50% (12/24) of S. aureus, 3.3% (1/30) of S. pseudintermedius and 25% (14/56) of other coagulase-positive staphylococci (CPS) were determined to be MDR. S. aureus isolates were more likely to be MDR compared with S. pseudintermedius. We did not find a significant statistical association between the use of oral or injectable antimicrobials in the prior year and the presence of MDR bacteria. The results suggest that drivers of antimicrobial resistance in household staphylococci may vary by bacterial species, which could have implications for one health intervention strategies for staphylococci and inform the investigation of other reverse zoonoses, such as COVID-19.

Molecular analysis of an increase in trimethoprim/sulfamethoxazole-resistant MRSA reveals multiple introductions into a tertiary care hospital, Germany 2012-19.

OBJECTIVES: Increasing spread of resistance could jeopardize the use of antifolates against MRSA infections. METHODS: We compared the prevalence of phenotypic trimethoprim/sulfamethoxazole resistance in 20 534 clinical Staphylococcus aureus isolates (19 096 MSSA and 1438 MRSA) of non-redundant patients at Heidelberg University Hospital over 8 years and performed WGS on trimethoprim/sulfamethoxazole-resistant MRSA. RESULTS: From 2012 to 2019, trimethoprim/sulfamethoxazole resistance in MSSA (674/19 096; 3.5%) ranged between 1.5% and 7.2% and in MRSA (135/1438; 9.4%) between 0.5% and 20.2%, reaching a peak in 2016 and 2018, respectively (Ptrend < 0.001). Trimethoprim/sulfamethoxazole resistance was more likely in outpatients than inpatients (P = 0.005), younger patients (P < 0.001), skin and soft tissue infections (SSTIs) (MRSA only, P = 0.05), submissions from pulmonology (MRSA only, P = 0.001), the upper respiratory tract (MSSA only, P < 0.001) and general surgery (MSSA only, P = 0.001). WGS of 76 trimethoprim/sulfamethoxazole-resistant MRSA revealed that 59% belonged to major pandemic CA-MRSA clones (ST22, ST8, ST398, ST772, ST30), 47% harboured Panton-Valentine leucocidin (PVL), 97% SCCmec IV/V, 71% dfrG and 28% dfrA. SNP-based phylogeny of trimethoprim/sulfamethoxazole-resistant MRSA core genomes favoured independent introduction over clonal expansion as the source, most prominently of dfrA+ trimethoprim/sulfamethoxazole-resistant ST22 MRSA from the Gaza Strip. CONCLUSIONS: The presented results support that trimethoprim/sulfamethoxazole-resistant S. aureus, formerly associated with SSTI from outpatients and S. aureus in the (sub)tropics, is on the rise in the temperate zone, potentially due to migration. Closer monitoring of trimethoprim/sulfamethoxazole resistance in S. aureus is recommended to safeguard the effectiveness of antifolate compounds.

Inhibitors of bacterial H2S biogenesis targeting antibiotic resistance and tolerance.

Emergent resistance to all clinical antibiotics calls for the next generation of therapeutics. Here we report an effective antimicrobial strategy targeting the bacterial hydrogen sulfide (H2S)-mediated defense system. We identified cystathionine γ-lyase (CSE) as the primary generator of H2S in two major human pathogens, Staphylococcus aureus and Pseudomonas aeruginosa, and discovered small molecules that inhibit bacterial CSE. These inhibitors potentiate bactericidal antibiotics against both pathogens in vitro and in mouse models of infection. CSE inhibitors also suppress bacterial tolerance, disrupting biofilm formation and substantially reducing the number of persister bacteria that survive antibiotic treatment. Our results establish bacterial H2S as a multifunctional defense factor and CSE as a drug target for versatile antibiotic enhancers.

ENDOGENOUS ENDOPHTHALMITIS IN THE SETTING OF COVID-19 INFECTION: A Case Series.

PURPOSE: To describe endogenous endophthalmitis in the setting of COVID-19 pneumonia. METHODS: Patients recovering from COVID-19 pneumonia who presented to our department with any or all of the following complaints: pain, watering, redness, and decreased vision were identified. All relevant data were collected for analysis. RESULTS: Three patients with endogenous endophthalmitis were identified. All patients had been treated for COVID-19 pneumonia and therefore had received remdesivir and systemic steroids; 2 of the 3 patients received tocilizumab. All patients received vitreous biopsy, vitrectomy, and intraocular antibiotic injection. Patient 1 demonstrated Klebsiella pneumoniae in blood culture, K. pneumoniae and Escherichia coli in urine culture, and K. pneumoniae in vitreous fluid, whereas Patients 2 and 3 demonstrated Stenotrophomonas maltophilia and methicillin-resistant Staphylococcus aureus in the blood and nasopharyngeal culture, respectively. Correspondingly, the same organism was cultured from vitreous in Patients 2 and 3. The visual acuity at the last follow-up in Patients 1 to 3 was 20/100, 20/80, and 20/40, respectively. The probable source of infection was identified in each as renal calculi, dental caries, and the pharynx, respectively. Real-time polymerase chain reaction demonstrated the presence of Severe Acute Respiratory Syndrome Coronavirus 2 in the vitreous fluid of Patient 1. CONCLUSION: We report good outcomes of early intervention for endogenous endophthalmitis in the setting of COVID-19 infection. We also document the presence of SARS-CoV-2 in vitreous.

Protective effect of SARS-CoV-2 preventive measures against ESKAPE and Escherichia coli infections.

BACKGROUND/OBJECTIVES: We investigated whether behavioral precautions adopted during Coronavirus disease (COVID-19) pandemic also influenced the spreading and multidrug resistance (MDR) of ESKAPEEc (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii [AB], Pseudomonas aeruginosa, Enterobacter spp and Escherichia Coli, [EC]) among Intensive Care Unit (ICU) patients. SUBJECTS/METHODS: We performed a single-center retrospective study in adult patients admitted to our COVID-19-free surgical ICU. Only patients staying in ICU for more than 48 hours were included. The ESKAPEEc infections recorded during the COVID-19 period (June 1, 2020 - February 28, 2021) and in the corresponding pre-pandemic period (June 1, 2019 - February 28, 2020) were compared. An interrupted time series analysis was performed to rule out possible confounders. RESULTS: Overall, 173 patients in the COVID-19 period and 132 in the pre-COVID-19 period were investigated. The ESKAPEEc infections were documented in 23 (13.3%) and 35 (26.5%) patients in the pandemic and the pre-pandemic periods, respectively (p = 0.005). Demographics, diagnosis, comorbidities, type of surgery, Simplified Acute Physiology Score II, length of mechanical ventilation, hospital and ICU length of stay, ICU death rate, and 28-day hospital mortality were similar in the two groups. In comparison with the pre-pandemic period, no AB was recorded during COVID-19 period, (p = 0.017), while extended-spectrum beta-lactamase-producing EC infections significantly decreased (p = 0.017). Overall, the ESKAPEEc isolates during pandemic less frequently exhibited multidrug-resistant (p = 0.014). CONCLUSIONS: These findings suggest that a robust adherence to hygiene measures together with human contact restrictions in a COVID-19 free ICU might also restrain the transmission of ESKAPEEc pathogens.

The Impact of COVID-19 on Conjunctival Flora.

Purpose: This study aims to evaluate the effect of coronavirus disease 2019 (COVID-19) on conjunctival flora in patients hospitalized with COVID-19.Methods: This prospective, controlled study was conducted between June 2020 and December 2020. The study group consisted of 45 confirmed COVID-19 patients and 43 control subjects. The collected samples were inoculated into the Thioglycollate broth media without delay. The samples with growth were then passed on eosin methylene blue agar, sabouraud dextrose agar, chocolate agar, and 5% sheep blood agar solid media.Results: The mean age of the COVID-19 patients was 64.24 ± 15.4 years, and the control subjects were 59.72 ± 11.4 years. The culture positivity of conjunctiva samples in COVID-19 patients (95.6%) was statistically significantly higher than control subjects (76.7%) (p = .024). Coagulase-negative staphylococcus and Staphylococcus aureus' positivity was significantly higher in COVID-19 patients than control subjects (p < .05).Conclusion: Patients with COVID-19 demonstrate significantly higher culture positivity on conjunctival flora than the control subjects.

Right-sided infective endocarditis in association with a left-to-right shunt complicated by haemoptysis and acute renal failure: a case report.

BACKGROUND: Infective endocarditis has a relevant clinical impact due to its high morbidity and mortality rates. Right-sided endocarditis has lower complication rates than left-sided endocarditis. Common complications are multiple septic pulmonary embolisms, haemoptysis, and acute renal failure. Risk factors associated with right-sided infective endocarditis are commonly related to intravenous drug abuse, central venous catheters, or infections due to implantable cardiac devices. However, patients with congenital ventricular septal defects might be at high risk of endocarditis and haemodynamic complications. CASE PRESENTATION: In the following, we present the case of a 23-year-old man without a previous intravenous drug history with tricuspid valve Staphylococcus aureus endocarditis complicated by acute renal failure and haemoptysis caused by multiple pulmonary emboli. In most cases, right-sided endocarditis is associated with several common risk factors, such as intravenous drug abuse, a central venous catheter, or infections due to implantable cardiac devices. In this case, we found a small perimembranous ventricular septal defect corresponding to a type 2 Gerbode defect. This finding raised the suspicion of a congenital ventricular septal defect complicated by a postendocarditis aneurysmal transformation. CONCLUSIONS: Management of the complications of right-sided infective endocarditis requires a multidisciplinary approach. Echocardiographic approaches should include screening for ventricular septal defects in patients without common risk factors for tricuspid valve endocarditis. Patients with undiagnosed congenital ventricular septal defects are at high risk of infective endocarditis. Therefore, endocarditis prophylaxis after dental procedures and/or soft-tissue infections is highly recommended. An acquired ventricular septal defect is a very rare complication of infective endocarditis. Surgical management of small ventricular septal defects without haemodynamic significance is still controversial.

Toll-like receptor 2 downregulation and cytokine dysregulation predict mortality in patients with Staphylococcus aureus bacteremia.

BACKGROUND: Staphylococcus aureus bacteremia (SAB) presents heterogeneously, owing to the differences in underlying host conditions and immune responses. Although Toll-like receptor 2 (TLR2) is important in recognizing S. aureus, its function during S. aureus infection remains controversial. We aimed to examine the association of TLR2 expression and associated cytokine responses with clinical SAB outcomes. METHODS: Patients from a prospective SAB cohort at two tertiary-care medical centers were enrolled. Blood was sampled at several timepoints (≤5 d, 6-9 d, 10-13 d, 14-19 d, and ≥ 20 d) after SAB onset. TLR2 mRNA levels were determined via real-time PCR and serum tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-10 levels were analyzed with multiplex-high-sensitivity electrochemiluminescent ELISA. RESULTS: TLR2 levels varied among 59 SAB patients. On days 2-5, TLR2 levels were significantly higher in SAB survivors than in healthy controls (p = 0.040) and slightly but not significantly higher than non-survivors (p = 0.120), and SAB patients dying within 7 d had lower TLR2 levels than survivors (P = 0.077) although statistically insignificant. IL-6 and IL-10 levels were significantly higher in non-survivors than in survivors on days 2-5 post-bacteremia (P = 0.010 and P = 0.021, respectively), and those dying within 7 d of SAB (n = 3) displayed significantly higher IL-10/TNF-α ratios than the survivors did (P = 0.007). CONCLUSION: TLR2 downregulation and IL-6 and IL-10 concentrations suggestive of immune dysregulation during early bacteremia may be associated with mortality from SAB. TLR2 expression levels and associated cytokine reactions during early-phase SAB may be potential prognostic factors in SAB, although larger studies are warranted.

Engineering of a Dual-Recognition Ratiometric Fluorescent Nanosensor with a Remarkably Large Stokes Shift for Accurate Tracking of Pathogenic Bacteria at the Single-Cell Level.

Rapid, accurate, reliable, and risk-free tracking of pathogenic microorganisms at the single-cell level is critical to achieve efficient source control and prevent outbreaks of microbial infectious diseases. For the first time, we report a promising approach for integrating the concepts of a remarkably large Stokes shift and dual-recognition into a single matrix to develop a pathogenic microorganism stimuli-responsive ratiometric fluorescent nanoprobe with speed, cost efficiency, stability, ultrahigh specificity, and sensitivity. As a proof-of-concept, we selected the Gram-positive bacterium Staphylococcus aureus (S. aureus) as the target analyte model, which easily bound to its recognition aptamer and the broad-spectrum glycopeptide antibiotic vancomycin (Van). To improve the specificity and short sample-to-answer time, we employed classic noncovalent π-π stacking interactions as a driving force to trigger the binding of Van and aptamer dual-functionalized near-infrared (NIR) fluorescent Apt-Van-QDs to the surface of an unreported blue fluorescent π-rich electronic carbon nanoparticles (CNPs), achieving S. aureus stimuli-responsive ratiometric nanoprobe Apt-Van-QDs@CNPs. In the assembly of Apt-Van-QDs@CNPs, the blue CNPs (energy donor) and NIR Apt-Van-QDs (energy acceptor) became close to allow the fluorescence resonance energy transfer (FRET) process, leading to a remarkable blue fluorescence quenching for the CNPs at ∼465 nm and a clear NIR fluorescence enhancement for Apt-Van-QDs at ∼725 nm. In the presence of S. aureus, the FRET process from CNPs to Apt-Van-QDs was disrupted, causing the nanoprobe Apt-Van-QDs@CNPs to display a ratiometric fluorescent response to S. aureus, which exhibited a large Stokes shift of ∼260 nm and rapid sample-to-answer detection time (∼30.0 min). As expected, the nanoprobe Apt-Van-QDs@CNPs showed an ultrahigh specificity for ratiometric fluorescence detection of S. aureus with a good detection limit of 1.0 CFU/mL, allowing the assay at single-cell level. Moreover, we also carried out the precise analysis of S. aureus in actual samples with acceptable results. We believe that this work offers new insight into the rational design of efficient ratiometric nanoprobes for rapid on-site accurate screening of pathogenic microorganisms at the single-cell level in the early stages, especially during the worldwide spread of COVID-19 today.