When antibiotics fail: a clinical and microbiological perspective on antibiotic tolerance and persistence of Staphylococcus aureus.

Staphylococcus aureus is a major human pathogen causing a vast array of infections with significant mortality. Its versatile physiology enables it to adapt to various environments. Specific physiological changes are thought to underlie the frequent failure of antimicrobial therapy despite susceptibility in standard microbiological assays. Bacteria capable of surviving high antibiotic concentrations despite having a genetically susceptible background are described as 'antibiotic tolerant'. In this review, we put current knowledge on environmental triggers and molecular mechanisms of increased antibiotic survival of S. aureus into its clinical context. We discuss animal and clinical evidence of its significance and outline strategies to overcome infections with antibiotic-tolerant S. aureus.

Zwischen Traum und Trauma - Aufbau und Betrieb einer Kohortenstation für Patient_innen mit COVID-19 in einem Akutspital - Eine Fallstudie.

Between dream and distress - Setting up and running a cohort ward for COVID-19 Patients at an acute hospital - A case study Abstract. Background: In the context of the pandemic, hospitals must be able to care for COVID-19 patients within a very short timeframe. OBJECTIVE: Description of the setting up of a cohort ward for patients with COVID-19 on a surgical ward including the development of the nursing team. METHODS: The intrinsic retrospective case study describes the situation, identifies special phenomena in a reflective manner and links them to existing knowledge. Data were anecdotal, routine data were collected in the context of nursing practice development. RESULTS: Setting up the cohort ward in a Swiss hospital consisted of structural and technical planning, infection control measures, the establishment of interprofessional structures, and internal communication. During the four-week operation, 71 patients were treated. The use of practice development methodology initiated a cultural change. The reflection describes a field of tension between "dream and distress": As a dream, the lived experience of optimal care, with well-functioning processes, sufficient material, sufficient personnel and a very good interprofessional cooperation was evaluated. Distress in the form of high infection rates as well as psychological and physical stress did not occur. After the cohort ward was closed, there was a risk working back in normal operations based on existing economical and organizational conditions, with the knowledge that a different cooperation and organization is possible. CONCLUSIONS: Positive experiences from the "crisis mode" should be used to further develop essential operations during normal times.

High Mortality of Non-Fournier Necrotizing Fasciitis With Enterobacteriales: Time to Rethink Classification?

This cohort study describes mortality predictors of necrotizing fasciitis (NF). Higher age, chronic kidney disease, and higher Charlson score increased the mortality rate. Mortality was >3 times higher in monomicrobial gram-negative NF than in type I or type II NF. Highest mortality was found with Enterobacteriales in non-Fournier NF.

Implementation and evaluation of an algorithm for the management of scabies outbreaks.

BACKGROUND: Infestations with scabies mites are a global burden affecting individuals of all ages, classes and ethnicities. As poor sanitation and overcrowding favor the transmission of this highly contagious disease, epidemic outbreaks are frequently observed among displaced persons and asylum seekers. Due to the growing influx of refugees during the last years, public health authorities in host countries are frequently confronted with the challenge to treat individuals with diagnosed or suspected scabies promptly and effectively to avoid further spreading of the infestation. This study aimed to establish a straightforward and efficient algorithm for rapid screening and treatment of large numbers of patients with confirmed or suspected scabies infestations. METHODS: Forty-eight individuals (58% males, mean age 22.4 yrs.) from Syria with suspected scabies infestation were allocated to 3 colour-coded groups: (1) no signs or symptoms of infestation, (2) itch only, and (3) itch and typical skin lesions. Patients were treated with a single (group 1) or two doses of oral ivermectin at an interval of 7 days (group 2), or with a combination of 2 doses of ivermectin plus 2 applications of permethrin ointment at an interval of 7 days (group 3). Follow-ups were performed 4 weeks after initial treatments. RESULTS: All individuals with signs and/or symptoms of infestation had improved skin lesion; in 10/11 (90.9%) lesion had completely resolved. All individuals with initial itch only (n = 32) reported improvement of its intensity or complete resolution. None of the patients of group 1 developed itch or skin lesions. The algorithm was reapplied in 4 individuals (8.3%) after 4 weeks and the outbreak was completely controlled after 8 weeks. Colour-coding ensured fast flow of information between health-care providers at the interfaces of the algorithm. CONCLUSIONS: Our algorithm proved to be both highly efficient for treatment of large numbers of patients with suspected or diagnosed scabies infestation as well as for prevention of spreading of the disease. Hence, this algorithm is well suited for the management of scabies mass outbreaks.

Preventing Implant-Associated Infections by Silver Coating.

Implant-associated infections (IAIs) are a dreaded complication mainly caused by biofilm-forming staphylococci. Implant surfaces preventing microbial colonization would be desirable. We examined the preventive effect of a silver-coated titanium-aluminum-niobium (TiAlNb) alloy. The surface elicited a strong, inoculum-dependent activity againstStaphylococcus epidermidisandStaphylococcus aureusin an agar inhibition assay. Gamma sterilization and alcohol disinfection did not alter the effect. In a tissue cage mouse model, silver coating of TiAlNb cages prevented perioperative infections in an inoculum-dependent manner and led to a 100% prevention rate after challenge with 2 × 10(6)CFU ofS. epidermidisper cage. InS. aureusinfections, silver coating had only limited effect. Similarly, daptomycin or vancomycin prophylaxis alone did not preventS. aureusinfections. However, silver coating combined with daptomycin or vancomycin prophylaxis thwarted methicillin-resistantS. aureusinfections at a prevention rate of 100% or 33%, respectively. Moreover, silver release from the surface was independent of infection and occurred rapidly after implantation. On day 2, a peak of 82 µg Ag/ml was reached in the cage fluid, corresponding to almost 6× the MIC of the staphylococci. Cytotoxicity toward leukocytes in the cage was low and temporary. Surrounding tissue did not reveal histological signs of silver toxicity.In vitro, no emergence of silver resistance was observed in several clinical strains of staphylococci upon serial subinhibitory silver exposures. In conclusion, our data demonstrate that silver-coated TiAlNb is potent for prevention of IAIs and thus can be considered for clinical application.

The myocutaneous gastrocnemius flap for periprosthetic joint infection of the knee.

Purpose: Periprosthetic joint infection (PJI) following total knee arthroplasty (TKA) presents significant challenges, especially in elderly and comorbid patients, often necessitating revision surgeries. We report on a series of patients with confirmed PJI of the knee and concomitant soft-tissue/extensor apparatus defects, treated by using pedicled myocutaneous medial or lateral sural artery perforator (MSAP/LSAP) gastrocnemius flaps. Methods: Our retrospective study at the Center for Musculoskeletal Infections, included patients with knee PJI undergoing pedicled myocutaneous MSAP/LSAP gastrocnemius flap reconstruction for combined soft tissue and extensor apparatus defects. The tendinous back of the gastrocnemius muscle was used and, if required, the Achilles tendon for extensor apparatus reconstruction, with the skin island addressing the cutaneous defect. Perioperative complications and postoperative outcomes after 1 year were evaluated, including functional and clinical assessments with the American Knee Society Score (AKSS). Results: Eight patients (mean age 73 years; five female) were included, predominantly with Staphylococcus aureus infections. Six patients involved isolated MSAP flaps, two were extended with the Achilles tendon. The median time for wound healing was 9 days. Short-term follow-up showed successful reconstruction in seven patients, with minor wound dehiscence in one patient. One patient required flap revision for a perigenicular haemato-seroma and two patients were diagnosed with new haematogenous PJI infection. Significant improvement in AKSS scores after surgery was observed (functional AKSS: median 33-85; clinical AKSS: median 64-91, p = 0.001). Conclusion: Pedicled myocutaneous MSAP/LSAP gastrocnemius flaps offer a safe, reliable and versatile option for reconstructing combined soft tissue and extensor apparatus defects in PJI after TKA. This approach yields excellent functional outcomes with minimal peri- and postoperative complications, which is particularly beneficial in elderly and comorbid patients and feasible in settings without microsurgical availability. Level of evidence: Level IV.

A Far-Red Fluorescent Probe to Visualize Gram-Positive Bacteria in Patient Samples.

Gram-positive bacteria, in particular Staphylococcus aureus (S. aureus), are the leading bacterial cause of death in high-income countries and can cause invasive infections at various body sites. These infections are associated with prolonged hospital stays, a large economic burden, considerable treatment failure, and high mortality rates. So far, there is only limited knowledge about the specific locations where S. aureus resides in the human body during various infections. Hence, the visualization of S. aureus holds significant importance in microbiological research. Herein, we report the development and validation of a far-red fluorescent probe to detect Gram-positive bacteria, with a focus on staphylococci, in human biopsies from deep-seated infections. This probe displays strong fluorescence and low background in human tissues, outperforming current tools for S. aureus detection. Several applications are demonstrated, including fixed- and live-cell imaging, flow cytometry, and super-resolution bacterial imaging.

Secondary attack rate following on-site isolation of patients with suspected COVID-19 in multiple-bed rooms.

The implementation of isolation precautions for patients with suspected Coronavirus Disease 2019 (COVID-19) and pending test results is resource intensive. Due to the limited availability of single-bed rooms at our institution, we isolated patients with suspected COVID-19 together with patients without suspected COVID-19 on-site in multiple-bed rooms until SARS-CoV-2-test results were available. We evaluated the likelihood of SARS-CoV-2 transmission to individuals sharing the room with patients isolated on-site. This observational study was performed at the University Hospital Basel, Switzerland, from 03/20 - 11/20. Secondary attack rates were compared between patients hospitalized in multiple-bed rooms and exposed to individuals subjected to on-site isolation precautions (on-site isolation group), and patients exposed to individuals initially not identified as having COVID-19, and not placed under isolation precautions until the diagnosis was suspected (control group). Transmission events were confirmed by whole-genome sequencing. Among 1,218 patients with suspected COVID-19, 67 (5.5%) tested positive for SARS-CoV-2. Of these, 21 were isolated on-site potentially exposing 27 patients sharing the same room. Median contact time was 12 h (interquartile range 7-18 h). SARS-CoV-2 transmission was identified in none of the patients in the on-site isolation group vs. 10/63 (15.9%) in the control group (p = 0.03). Isolation on-site of suspected COVID-19-patients in multiple-bed rooms avoided single-room occupancy and subsequent in-hospital relocation for many patients without confirmed SARS-CoV-2-infection. The absence of secondary transmission among the exposed patients in the on-site isolation group allows for assessment of the risk/benefit ratio of this strategy given the limitation of a small sample size.

A qualitative study on the perception of infection prevention and control measures among healthcare workers without patient contact during the SARS-CoV-2 pandemic.

We conducted a qualitative interview-based study to examine the perception of infection prevention and control (IPC) measures implemented during the COVID-19 pandemic among healthcare workers (HCWs) without patient contact in a tertiary academic care center. We compared these findings to those derived from interviews of HCWs with patient contact from the same institution using the same study design. The following main four themes were identified: (1) As for HCWs with patient contact, transparent communication strongly contributes to employees' sense of security. (2) Information on personal protective equipment (PPE) usage needs to be stratified according to different educational backgrounds and professions. (3) Consistency of IPC measures was positively perceived yet a desire for constant reminders to counteract the fatigue effect played a more significant role for HCWs without patient contact. (4) As compared to HCWs with patient contact, HCWs without patient contact preferred uniform digital training resources rather than more face-to-face training. This study shows that the needs of HCWs with and without patient contact differ and need to be considered in pandemic management.

A systematic outbreak investigation of SARS-CoV-2 transmission clusters in a tertiary academic care center.

BACKGROUND: We sought to decipher transmission pathways in healthcare-associated infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within our hospital by epidemiological work-up and complementary whole genome sequencing (WGS). We report the findings of the four largest epidemiologic clusters of SARS-CoV-2 transmission occurring during the second wave of the pandemic from 11/2020 to 12/2020. METHODS: At the University Hospital Basel, Switzerland, systematic outbreak investigation is initiated at detection of any nosocomial case of SARS-CoV-2 infection, as confirmed by polymerase chain reaction, occurring more than five days after admission. Clusters of nosocomial infections, defined as the detection of at least two positive patients and/or healthcare workers (HCWs) within one week with an epidemiological link, were further investigated by WGS on respective strains. RESULTS: The four epidemiologic clusters included 40 patients and 60 HCWs. Sequencing data was available for 70% of all involved cases (28 patients and 42 HCWs), confirmed epidemiologically suspected in house transmission in 33 cases (47.1% of sequenced cases) and excluded transmission in the remaining 37 cases (52.9%). Among cases with identical strains, epidemiologic work-up suggested transmission mainly through a ward-based exposure (24/33, 72.7%), more commonly affecting HCWs (16/24, 66.7%) than patients (8/24, 33.3%), followed by transmission between patients (6/33, 18.2%), and among HCWs and patients (3/33, 9.1%, respectively two HCWs and one patient). CONCLUSIONS: Phylogenetic analyses revealed important insights into transmission pathways supporting less than 50% of epidemiologically suspected SARS-CoV-2 transmissions. The remainder of cases most likely reflect community-acquired infection randomly detected by outbreak investigation. Notably, most transmissions occurred between HCWs, possibly indicating lower perception of the risk of infection during contacts among HCWs.

Impact of adherence to individual quality-of-care indicators on the prognosis of bloodstream infection due to Staphylococcus aureus: a prospective observational multicentre cohort.

OBJECTIVES: To analyse the adherence and impact of quality-of-care indicators (QCIs) in the management of Staphylococcus aureus bloodstream infection in a prospective and multicentre cohort. METHODS: Analysis of the prospective, multicentre international S. Aureus Collaboration cohort of S. Aureus bloodstream infection cases observed between January 2013 and April 2015. Multivariable analysis was performed to evaluate the impact of adherence to QCIs on 90-day mortality. RESULTS: A total of 1784 cases were included. Overall, 90-day mortality was 29.9% and mean follow-up period was 118 days. Adherence was 67% (n = 1180/1762) for follow-up blood cultures, 31% (n = 416/1342) for early focus control, 77.6% (n = 546/704) for performance of echocardiography, 75.5% (n = 1348/1784) for adequacy of targeted antimicrobial therapy, 88.6% (n = 851/960) for adequacy of treatment duration in non-complicated bloodstream infections and 61.2% (n = 366/598) in complicated bloodstream infections. Full bundle adherence was 18.4% (n = 328/1784). After controlling for immortal time bias and potential confounders, focus control (adjusted hazard ratio = 0.76; 95% CI, 0.59-0.99; p 0.038) and adequate targeted antimicrobial therapy (adjusted hazard ratio = 0.75; 95% CI, 0.61-0.91; p 0.004) were associated with low 90-day mortality. DISCUSSION: Adherence to QCIs in S. Aureus bloodstream infection did not reach expected rates. Apart from the benefits of application as a bundle, focus control and adequate targeted therapy were independently associated with low mortality.

Perioperative myocardial injury and mortality after revision surgery for orthopaedic device-related infection.

AIMS: Periprosthetic joint infections (PJIs) and fracture-related infections (FRIs) are associated with a significant risk of adverse events. However, there is a paucity of data on cardiac complications following revision surgery for PJI and FRI and how they impact overall mortality. Therefore, this study aimed to investigate the risk of perioperative myocardial injury (PMI) and mortality in this patient cohort. METHODS: We prospectively included consecutive patients at high cardiovascular risk (defined as age ≥ 45 years with pre-existing coronary, peripheral, or cerebrovascular artery disease, or any patient aged ≥ 65 years, plus a postoperative hospital stay of > 24 hours) undergoing septic or aseptic major orthopaedic surgery between July 2014 and October 2016. All patients received a systematic screening to reliably detect PMI, using serial measurements of high-sensitivity cardiac troponin T. All-cause mortality was assessed at one year. Multivariable logistic regression models were applied to compare incidence of PMI and mortality between patients undergoing septic revision surgery for PJI or FRI, and patients receiving aseptic major bone and joint surgery. RESULTS: In total, 911 consecutive patients were included. The overall perioperative myocardial injury (PMI) rate was 15.4% (n = 140). Septic revision surgery for PJI was associated with a significantly higher PMI rate (43.8% (14/32) vs 14.5% (57/393); p = 0.001) and one-year mortality rate (18.6% (6/32) vs 7.4% (29/393); p = 0.038) compared to aseptic revision or primary arthroplasty. The association with PMI persisted in multivariable analysis with an adjusted odds ratio (aOR) of 4.7 (95% confidence interval (CI) 2.1 to 10.7; p < 0.001), but was not statistically significant for one-year mortality (aOR 1.9 (95% CI 0.7 to 5.4; p = 0.240). PMI rate (15.2% (5/33) vs 14.1% (64/453)) and one-year mortality (15.2% (5/33) vs 9.1% (41/453)) after FRI revision surgery were comparable to aseptic long-bone fracture surgery. CONCLUSION: Patients undergoing revision surgery for PJI were at a risk of PMI and death compared to those undergoing aseptic arthroplasty surgery. Screening for PMI and treatment in specialized multidisciplinary units should be considered in major bone and joint infections. Cite this article: Bone Joint J 2022;104-B(6):696-702.

A qualitative study on safety perception among healthcare workers of a tertiary academic care center during the SARS-CoV-2 pandemic.

BACKGROUND: Protecting healthcare workers (HCWs) from exposure to SARS-CoV-2 during patient care is central to managing the current pandemic. Higher levels of trust in personal protective equipment (PPE) and infection prevention and control (IPC) strategies have been previously related to lower levels of emotional exhaustion, yet little is known on how to achieve such a perception of safety. We thus sought to identify institutional actions, strategies and policies related to HCWs' safety perception during the early phase of the pandemic at a tertiary care center in Switzerland by interviewing HCWs from different clinics, professions, and positions. METHODS: For this qualitative study, 36 face-to-face semi-structured interviews were performed. Interviews were based on a guide that addressed the perception of institutional strategies and policies during the first phase of the pandemic in March 2020. The participants included doctors (n = 19) and nurses (n = 17) in senior and non-senior positions from eight clinics in the University Hospital Basel, Switzerland, all involved in patient care. All interviews were audio-recorded and transcribed verbatim. Data were analyzed using qualitative content analysis and organized using MAXQDA (VERBI Software GmbH, Berlin). FINDINGS: Five recurring themes were identified to affect HCWs' perception of their safety during the SARS-CoV-2 pandemic: (1) transparency and clarity of information, (2) communication on the availability of PPE (with the provision of information alone increasing the feeling of safety even if supplies of PPE were reported as low), (3) uniformity and consistency of guidelines, (4) digital resources to support face-to-face teaching (although personal information transfer is still being considered superior in terms of strengthening safety perception) and (5) support and appreciation for the work performed. CONCLUSIONS: This study identifies institutional policies and actions influencing HCWs' safety perception during the first wave of the COVID-19 pandemic, the most important of which is the factor of transparent communication. This knowledge reveals potential areas of action critical to improving preparedness and management in hospitals faced with an infectious disease threat.

Soft-tissue reconstruction in lower-leg fracture-related infections: An orthoplastic outcome and risk factor analysis.

Introduction Fracture-related infection (FRI) is a severe post-traumatic complication which is occasionally accompanied by a deficient or even avital soft-tissue envelope. In these cases, a thoroughly planned orthoplastic approach is imperative as a vital and intact soft-tissue envelope is mandatory to achieve fracture union and infection eradication. The aim of this study was, to analyse if soft-tissue reconstruction (STR) without complications is associated with a better long-term outcome compared to FRI patients with STR complications. In particular, it was investigated if primary flap failure represented a risk factor for compromised fracture union and recurrence of infection. Patients and Methods Patients with a lower leg FRI requiring STR (local, pedicled and free flaps) who were treated from 2010-18 at the University Hospital Basel were included in this retrospective analysis. The main outcome measure was the success rate of STR, further outcome measures were fracture nonunion and recurrence of infection. Results Overall, 145 patients with lower leg FRI were identified, of whom 58 (40%) received STR (muscle flaps: n = 38, fascio-cutaneous flaps: n=19; composite osteo-cutaneous flap: n = 1). In total seven patients required secondary STR due to primary flap failure. All failures and flap-related complications occurred within the first three weeks after surgery. Secondary STR was successful in all cases. A high Charlson Comorbidity Index Score was a significant risk factor for flap failure (p = 0.011). Out of the 43 patients who completed the 9-month follow-up, 11 patients presented with fracture nonunion and 12 patients with a recurrent infection. Polymicrobial infection was a significant risk factor for fracture nonunion (p = 0.002). Primary flap failure was neither a risk factor for compromised fracture consolidation (p = 0.590) nor for recurrence of infection (p = 0.508). Conclusion: A considerable number of patients with lower-leg FRI required STR. This patient subgroup is complex and rich in complications and the long-term composite outcome demonstrated a high rate of compromised fracture consolidation and recurrent infections. It appears that secondary STR should be performed, as primary flap failure was neither a risk factor for compromised fracture consolidation nor for recurrence of infection. We propose to monitor these patients closely for three weeks after STR.

The influence of duration of infection on outcome of debridement and implant retention in fracture-related infection.

AIMS: The principle strategies of fracture-related infection (FRI) treatment are debridement, antimicrobial therapy, and implant retention (DAIR) or debridement, antimicrobial therapy, and implant removal/exchange. Increasing the period between fracture fixation and FRI revision surgery is believed to be associated with higher failure rates after DAIR. However, a clear time-related cut-off has never been scientifically defined. This systematic review analyzed the influence of the interval between fracture fixation and FRI revision surgery on success rates after DAIR. METHODS: A systematic literature search was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in PubMed (including MEDLINE), Embase, and Web of Science Core Collection, investigating the outcome after DAIR procedures of long bone FRIs in clinical studies published until January 2020. RESULTS: Six studies, comprising 276 patients, met the inclusion criteria. Data from this review showed that with a short duration of infection (up to three weeks) and under strict preconditions, retention of the implant is associated with high success rates of 86% to 100%. In delayed infections with a fracture fixation-FRI revision surgery interval of three to ten weeks, absence of recurrent infection was reported in 82% to 89%. Data on late FRIs, with a fracture fixation-FRI revision surgery interval of more than ten weeks, are scarce and a success rate of 67% was reported. CONCLUSION: Acute/early FRI, with a short duration of infection, can successfully be treated with DAIR up to ten weeks after osteosynthesis. The limited available data suggest that chronic/late onset FRI treated with DAIR may be associated with a higher rate of recurrence. Successful outcome is dependent on managing all aspects of the infection. Thus, time from fracture fixation is not the only factor that should be considered in treatment planning of FRI. Due to the heterogeneity of the available data, these conclusions have to be interpreted with caution. Cite this article: Bone Joint J 2021;103-B(2):213-221.

Diagnosing Fracture-Related Infection: Current Concepts and Recommendations.

Fracture-related infection (FRI) is a severe complication after bone injury and can pose a serious diagnostic challenge. Overall, there is a limited amount of scientific evidence regarding diagnostic criteria for FRI. For this reason, the AO Foundation and the European Bone and Joint Infection Society proposed a consensus definition for FRI to standardize the diagnostic criteria and improve the quality of patient care and applicability of future studies regarding this condition. The aim of this article was to summarize the available evidence and provide recommendations for the diagnosis of FRI. For this purpose, the FRI consensus definition will be discussed together with a proposal for an update based on the available evidence relating to the diagnostic value of clinical parameters, serum inflammatory markers, imaging modalities, tissue and sonication fluid sampling, molecular biology techniques, and histopathological examination. Second, recommendations on microbiology specimen sampling and laboratory operating procedures relevant to FRI will be provided. LEVEL OF EVIDENCE:: Diagnostic Level V. See Instructions for Authors for a complete description of levels of evidence.

Recommendations for Systemic Antimicrobial Therapy in Fracture-Related Infection: A Consensus From an International Expert Group.

Fracture-related infection (FRI) is a major complication in musculoskeletal trauma and one of the leading causes of morbidity. Standardization of general treatment strategies for FRI has been poor. One of the reasons is the heterogeneity in this patient population, including various anatomical locations, multiple fracture patterns, different degrees of soft-tissue injury, and different patient conditions. This variability makes treatment complex and hard to standardize. As these infections are biofilm-related, surgery remains the cornerstone of treatment, and this entails multiple key aspects (eg, fracture fixation, tissue sampling, debridement, and soft-tissue management). Another important aspect, which is sometimes less familiar to the orthopaedic trauma surgeon, is systemic antimicrobial therapy. The aim of this article is to summarize the available evidence and provide recommendations for systemic antimicrobial therapy with respect to FRI, based on the most recent literature combined with expert opinion. LEVEL OF EVIDENCE:: Therapeutic Level V. See Instructions for Authors for a complete description of levels of evidence.