Non-antimicrobial adjuvant strategies to tackle biofilm-related Staphylococcus aureus prosthetic joint infections

Staphylococcus aureus frequently causes community-and hospital-acquired infections. S. aureus attachment followed by biofilm formation on tissues and medical devices plays a significant role in the establishment of chronic infections. Staphylococcal biofilms encase bacteria in a matrix and protect the cells from antimicrobials and the immune system, resulting in infections that are highly resistant to treatment. The biology of biofilms is complex and varies between organisms. In this review, we focus our discussion on S. aureus biofilms and describe the stages of their formation. We particularly emphasize genetic and biochemical processes that may be vulnerable to novel treatment approaches. Against this background, we discuss treatment strategies that have been successful in animal models of S. aureus biofilm-related infection and consider their possible use for the prevention and eradication of biofilm-related S. aureus prosthetic joint infection

Is boosting the immune system in sepsis appropriate?

A relative immunosuppression is observed in patients after sepsis, trauma, burns, or any severe insults. It is currently proposed that selected patients will benefit from treatment aimed at boosting their immune systems. However, the host immune response needs to be considered in context with pathogen-type, timing, and mainly tissue specificity. Indeed, the immune status of leukocytes is not universally decreased and their activated status in tissues contributes to organ failure. Accordingly, any new immune-stimulatory therapeutic intervention should take into consideration potentially deleterious effects in some situations

Tropical Australian health-data linkage shows excess mortality following severe infectious disease is present in the short-term and long-term after hospital discharge

Background: In this study, we aimed to assess the risk factors associated with mortality due to an infectious disease over the short-, medium-, and long-term based on a data-linkage study for patients discharged from an infectious disease unit in North Queensland, Australia, between 2006 and 2011. Methods: Age-sex standardised mortality rates (SMR) for different subgroups were estimated, and the Kaplan-Meier method was used to estimate and compare the survival experience among different groups. Results: Overall, the mortality rate in the hospital cohort was higher than expected in comparison with the Queensland population (SMR: 15.3, 95%CI: 14.9–15.6). The long-term mortality risks were significantly higher for severe infectious diseases than non-infectious diseases for male sex, Indigenous, residential aged care and elderly individuals. Conclusion: In general, male sex, Indigenous status, age and comorbidity were associated with an increased hazard for all-cause death

Urinary tract infections due to extended-spectrum beta-lactamase-producing Gram-negative bacteria: identification of risk factors and outcome predictors in an Australian tertiary referral hospital

Summary Extended-spectrum beta-lactamase-expressing Gram-negative bacilli (ESBL-GNB) now commonly cause community-acquired infections, including urinary tract infections (UTI), and represent a challenge for practitioners in choosing empirical antibiotics. The aim of this study was to describe the epidemiology and clinical characteristics of UTIs/bacteriuria due to ESBL-GNB in Australia. At a single-site tertiary referral hospital, 100 cases with UTIs/bacteriuria due to ESBL-GNB were matched to 100 cases where UTIs/bacteriuria were caused by organisms matching the ESBL bacterial species that had routine susceptibility to antibiotics. Potential risk factors for ESBL-GNB UTI/bacteriuria and differences in clinical outcomes were identified. Length of admission prior to positive sample (odds ratio (OR) 1.3, p=0.03, per week), exposure to antibiotics (OR 5.7, p<0.001), return from overseas travel (OR 6.5, p=0.002), and nursing home residency (OR 4.2, p=0.03) were identified as risk factors associated with ESBL-GNB UTI/bacteriuria in the multivariate analysis. In addition, ESBL-GNB-infected cases subsequently had a longer inpatient stay (median 6 vs. 2 days, p=0.002) and were admitted to the intensive care unit more frequently (28/100 vs. 8/100, p<0.001). Our results emphasize the need for culture of a mid-stream urine specimen prior to commencing antibacterials, especially in patients with the risk factors identified herein associated with ESBL-GNB UTI/bacteriuria

Hospitalisations related to lower respiratory tract infections in Northern Queensland

Abstract Objective: To investigate the admission characteristics and hospital outcomes for patients admitted with lower respiratory tract infections (LRTI) in Northern Queensland. Methods: We perform a retrospective analysis of the data covering an 11‐year period, 2006–2016. Length of hospital stay (LOS) is modelled by negative binomial regression and heterogeneous effects are checked using interaction terms. Results: A total of 11,726 patients were admitted due to LRTI; 2,430 (20.9%) were of Indigenous descent. We found higher hospitalisations due to LRTI for Indigenous than non‐Indigenous patients, with a disproportionate increase in hospitalisations occurring during winter. The LOS for Indigenous patients was higher by 2.5 days [95%CI: ‐0.15; 5.05] than for non‐Indigenous patients. The average marginal effect of 17.5 [95%CI: 15.3; 29.7] implies that the LOS for a patient, who was admitted to ICU, was higher by 17.5 days. Conclusions: We highlighted the increased burden of LRTIs experienced by Indigenous populations, with this information potentially being useful for enhancing community‐level policy making. Implications for public health: Future guidelines can use these results to make recommendations for preventative measures in Indigenous communities. Improvements in engagement and partnership with Indigenous communities and consumers can help increase healthcare uptake and reduce the burden of respiratory diseases

Effect of savirin in the prevention of biofilm-related Staphylococcus aureus prosthetic joint infection

Background: Most of the arthroplasty surgery failure due to prosthetic joint infections (PJI) is caused by biofilm-associated Staphylococcus aureus. In a recent experimental study, savirin has been used to prevent and treat S. aureus skin infections in animal models. We explored the application of savirin in a PJI mouse model to determine its utility as an adjunct therapy to prevent PJI. Materials and methods: The in-vitro antibacterial and antibiofilm activity of savirin, with or without antibiotics (cefazolin, rifampicin, and vancomycin), against S. aureus were investigated using broth microdilution and crystal violet staining method, respectively. The effect of savirin treatment on the expression of the key biofilm-related genes (icaA, icaD, eno, fib, ebps, and agr) in S. aureus was studied using quantitative reverse transcriptase polymerase chain reaction (qRTPCR). The in-vivo efficacy of savirin alone and with cefazolin to prevent S. aureus PJI was determined using a clinically relevant PJI mouse model. Mice were randomized into five groups (n = 8/group): 1) infected K-wire savirin treated group, 2) infected K-wire cefazolin treated group, 3) infected K-wire savirin plus cefazolin treated group, 4) infected K-wire PBS treated group, 5) sterile K-wire group. Savirin was administered subcutaneously immediately post-surgery and intravenous cefazolin was given on day seven. Results: Savirin inhibited planktonic and biofilm in-vitro growth of S. aureus, showed enhanced inhibitory activity when combined with antibiotics, and down-regulated the expression of key S. aureus biofilm-related genes (icaA, icaD, eno, fib, ebps, and agr). Savirin significantly reduced bacterial counts on joint implants in comparison with the PBS treated control, while savirin plus cefazolin reduced bacterial counts on both implants and peri-prosthetic tissues. Conclusion: Savirin adjuvant therapy may prevent biofilm formation and S. aureus PJI. This study gives baseline data for using savirin for the prevention as well as treatment of S. aureus PJI in future animal studies

Non-Antimicrobial Adjuvant Therapy Using Ticagrelor Reduced Biofilm-Related Staphylococcus aureus Prosthetic Joint Infection

Background: Prosthetic joint infection (PJI), frequently caused by Staphylococcus aureus, leads to a significant arthroplasty failure rate. Biofilm is a crucial virulence factor of S. aureus that is intrinsic to the pathogenesis of PJI. Biofilm-related infections are recalcitrant to antibiotic treatment. Surgical and antibiotic therapy could be combined with non-antibacterial adjuvants to improve overall treatment success. Ticagrelor, a P2Y12 receptor inhibitor antiplatelet drug, is known to have anti-staphylococcal antibacterial and antibiofilm activity. However, the molecular mechanism for ticagrelor’s antibiofilm activity and its efficacy in the treatment of S. aureus PJI are unknown. Methods: To study the in vitro antibacterial and antibiofilm activity of ticagrelor, broth microdilution and crystal violet staining method were used. Ticagrelor’s effect on the expression of S. aureus biofilm genes (icaA, icaD, ebps, fib, eno, and agr) was studied using the relative quantification method. To test ticagrelor’s in vivo efficacy to treat S. aureus PJI, mice were randomized into five groups (n = 8/group): infected femoral implants treated with ticagrelor alone; infected implants treated with cefazolin alone; infected implants treated with ticagrelor and cefazolin; infected implants treated with phosphate buffer solution (PBS)-positive controls, and sterile implants-negative controls. Ticagrelor was administered orally from day 4 to day 7 post-surgery, while cefazolin was injected intravenously on day 7. Results: Ticagrelor, alone and with selected antibiotics, showed in vitro antibacterial and antibiofilm activity against S. aureus. Strain-specific downregulation of biofilm-related genes, fib, icaD, ebps, and eno, was shown. In an animal model of biofilm-related S. aureus PJI, ticagrelor alone and combined with cefazolin significantly reduced bacterial concentrations on the implants compared with the positive control group. Ticagrelor significantly reduced bacterial dissemination to periprosthetic tissue compared with the positive controls. Conclusion: Ticagrelor adjuvant therapy reduced S. aureus PJI in an animal model. However, this study is very preliminary to make a conclusion on the clinical implication of the findings. Based on the current results, more studies are recommended to better understand its implication

A case control study reveals that polyomaviruria is significantly associated with interstitial cystitis and vesical ulceration

Objectives: To investigate whether polyomaviruses contribute to interstitial cystitis pathogenesis. Subjects and Methods: A prospective study was performed with 50 interstitial cystitis cases compared with 50 age-matched, disease-free controls for the frequency of polyomaviruria. Associations between polyomaviruria and disease characteristics were analysed in cases. Polyomavirus in urine and bladder tissue was detected with species (JC virus vs. BK virus) specific, real-time PCR. Results: Case patients were reflective of interstitial cystitis epidemiology with age range from 26–88 years (median 58) and female predominance (41/50 F). There was a significant increase in the frequency of polyomavirus shedding between cases and controls (p<0.02). Polyomavirus shedding, in particular BK viruria, was associated with vesical ulceration, a marker of disease severity, among interstitial cystitis cases after adjustment for age and sex (OR 6.8, 95% CI 1.89–24.4). There was a significant association among cases between the presence of BK viruria and response to intravesical Clorpactin therapy (OR 4.50, 95% CI 1.17–17.4). Conclusion: The presence of polyomaviruria was found to be associated with the ulcerative form of interstitial cystitis. Clorpactin, which has anti-DNA virus activity, was more likely to improve symptoms in the presence of BK viruria. These data from this pilot study suggest associations between polyomaviruria and interstitial cystitis warranting further investigation

Change in outbreak epicentre and its impact on the importation risks of COVID-19 progression: A modelling study

Background The outbreak of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) that was first detected in the city of Wuhan, China has now spread to every inhabitable continent, but now the attention has shifted from China to other epicentres. This study explored early assessment of the influence of spatial proximities and travel patterns from Italy on the further spread of SARS-CoV-2 worldwide. Methods Using data on the number of confirmed cases of COVID-19 and air travel data between countries, we applied a stochastic meta-population model to estimate the global spread of COVID-19. Pearson's correlation, semi-variogram, and Moran's Index were used to examine the association and spatial autocorrelation between the number of COVID-19 cases and travel influx (and arrival time) from the source country. Results We found significant negative association between disease arrival time and number of cases imported from Italy (r = −0.43, p = 0.004) and significant positive association between the number of COVID-19 cases and daily travel influx from Italy (r = 0.39, p = 0.011). Using bivariate Moran's Index analysis, we found evidence of spatial interaction between COVID-19 cases and travel influx (Moran's I = 0.340). Asia-Pacific region is at higher/extreme risk of disease importation from the Chinese epicentre, whereas the rest of Europe, South-America and Africa are more at risk from the Italian epicentre. Conclusion We showed that as the epicentre changes, the dynamics of SARS-CoV-2 spread change to reflect spatial proximities

Pandemic (H1N1) 2009 Risk for Frontline Health Care Workers

To determine whether frontline health care workers (HCWs) are at greater risk for contracting pandemic (H1N1) 2009 than nonclinical staff, we conducted a study of 231 HCWs and 215 controls. Overall, 79 (17.7%) of 446 had a positive antibody titer by hemagglutination inhibition, with 46 (19.9%) of 231 HCWs and 33 (15.3%) of 215 controls positive (OR 1.37, 95% confidence interval 0.84–2.22). Of 87 participants who provided a second serum sample, 1 showed a 4-fold rise in antibody titer; of 45 patients who had a nose swab sample taken during a respiratory illness, 7 had positive results. Higher numbers of children in a participant’s family and working in an intensive care unit were risk factors for infection; increasing age, working at hospital 2, and wearing gloves were protective factors. This highly exposed group of frontline HCWs was no more likely to contract pandemic (H1N1) 2009 influenza infection than nonclinical staff, which suggests that personal protective measures were adequate in preventing transmission