Type 2 Interleukin-4 Receptor Signaling in Neutrophils Antagonizes Their Expansion and Migration during Infection and Inflammation.

Neutrophils are the first immune cells recruited to sites of inflammation and infection. However, patients with allergic disorders such as atopic dermatitis show a paucity of skin neutrophils and are prone to bacterial skin infections, suggesting that allergic inflammation curtails neutrophil responses. Here we have shown that the type 2 cell signature cytokine interleukin-4 (IL-4) hampers neutrophil expansion and migration by antagonizing granulocyte colony-stimulating factor (G-CSF) and chemokine receptor-mediated signals. Cutaneous bacterial infection in mice was exacerbated by IL-4 signaling and improved with IL-4 inhibition, each outcome inversely correlating with neutrophil migration to skin. Likewise, systemic bacterial infection was worsened by heightened IL-4 activity, with IL-4 restricting G-CSF-induced neutrophil expansion and migration to tissues by affecting CXCR2-CXCR4 chemokine signaling in neutrophils. These effects were dependent on IL-4 acting through type 2 IL-4 receptors on neutrophils. Thus, targeting IL-4 might be beneficial in neutropenic conditions with increased susceptibility to bacterial infections.

Hyperinflammatory environment drives dysfunctional myeloid cell effector response to bacterial challenge in COVID-19.

COVID-19 displays diverse disease severities and symptoms including acute systemic inflammation and hypercytokinemia, with subsequent dysregulation of immune cells. Bacterial superinfections in COVID-19 can further complicate the disease course and are associated with increased mortality. However, there is limited understanding of how SARS-CoV-2 pathogenesis and hypercytokinemia impede the innate immune function against bacterial superinfections. We assessed the influence of COVID-19 plasma hypercytokinemia on the functional responses of myeloid immune cells upon bacterial challenges from acute-phase COVID-19 patients and their corresponding recovery-phase. We show that a severe hypercytokinemia status in COVID-19 patients correlates with the development of bacterial superinfections. Neutrophils and monocytes derived from COVID-19 patients in their acute-phase showed an impaired intracellular microbicidal capacity upon bacterial challenges. The impaired microbicidal capacity was reflected by abrogated MPO and reduced NETs production in neutrophils along with reduced ROS production in both neutrophils and monocytes. Moreover, we observed a distinct pattern of cell surface receptor expression on both neutrophils and monocytes, in line with suppressed autocrine and paracrine cytokine signaling. This phenotype was characterized by a high expression of CD66b, CXCR4 and low expression of CXCR1, CXCR2 and CD15 in neutrophils and low expression of HLA-DR, CD86 and high expression of CD163 and CD11b in monocytes. Furthermore, the impaired antibacterial effector function was mediated by synergistic effect of the cytokines TNF-α, IFN-γ and IL-4. COVID-19 patients receiving dexamethasone showed a significant reduction of overall inflammatory markers in the plasma as well as exhibited an enhanced immune response towards bacterial challenge ex vivo. Finally, broad anti-inflammatory treatment was associated with a reduction in CRP, IL-6 levels as well as length of ICU stay and ventilation-days in critically ill COVID-19 patients. Our data provides insights into the transient functional dysregulation of myeloid immune cells against subsequent bacterial infections in COVID-19 patients and describe a beneficial role for the use of dexamethasone in these patients.

Human monocytes undergo functional re-programming during sepsis mediated by hypoxia-inducible factor-1α.

Sepsis is characterized by a dysregulated inflammatory response to infection. Despite studies in mice, the cellular and molecular basis of human sepsis remains unclear and effective therapies are lacking. Blood monocytes serve as the first line of host defense and are equipped to recognize and respond to infection by triggering an immune-inflammatory response. However, the response of these cells in human sepsis and their contribution to sepsis pathogenesis is poorly understood. To investigate this, we performed a transcriptomic, functional, and mechanistic analysis of blood monocytes from patients during sepsis and after recovery. Our results revealed the functional plasticity of monocytes during human sepsis, wherein they transited from a pro-inflammatory to an immunosuppressive phenotype, while enhancing protective functions like phagocytosis, anti-microbial activity, and tissue remodeling. Mechanistically, hypoxia inducible factor-1α (HIF1α) mediated this functional re-programming of monocytes, revealing a potential mechanism for their therapeutic targeting to regulate human sepsis.

Improving antimicrobial treatment in terms of antimicrobial stewardship and health costs by an OPAT service.

PURPOSE: Outpatient parenteral antimicrobial therapy (OPAT) is a standard for antimicrobial therapy internationally. With this prospective cohort study, we aimed to assess the impact of an OPAT service as part of antimicrobial stewardship (AMS) and evaluate the safety and efficiency of the program while illuminating the financial benefit for the hospital. METHODS: Socio-demographic data, treatment regimen and outcomes were prospectively recorded for all patients assigned to the program of the OPAT unit of the University Hospital of Zurich between November 2018 and September 2022. RESULTS: In total, we recorded 303 OPAT assignments of which 260 resulted in effective OPAT episodes. The 260 OPAT episodes were further optimized toward the choice of antimicrobial agent (n = 18) and length of therapy (n = 6). Moreover, OPAT resulted in alteration of patient assessment and care led by AMS strategies in 247 of 260 episodes (95%). While the bed days saved per year increased consistently with time, a total of 3934 in-hospital treatment days were saved amounting to a cost saving of 9,835,000 CHF over 47 months. Adverse events were recorded in 46 cases whilst only two of these have been the reason for readmission during OPAT treatment. Clinical cure was noted in 77% (199/260) and was negatively associated with Charlson Comorbidity Index (CCI; OR per 1 unit higher 0.85 (95% CI 0.78-0.93)). CONCLUSION: This study demonstrates the impact of an OPAT service in the framework of AMS as well as its benefits for the hospital whilst preserving safety and efficacy for the patient's parenteral antimicrobial treatment.

Molecular reprogramming and phenotype switching in Staphylococcus aureus lead to high antibiotic persistence and affect therapy success.

Staphylococcus aureus causes invasive infections and easily acquires antibiotic resistance. Even antibiotic-susceptible S. aureus can survive antibiotic therapy and persist, requiring prolonged treatment and surgical interventions. These so-called persisters display an arrested-growth phenotype, tolerate high antibiotic concentrations, and are associated with chronic and recurrent infections. To characterize these persisters, we assessed S. aureus recovered directly from a patient suffering from a persistent infection. We show that host-mediated stress, including acidic pH, abscess environment, and antibiotic exposure promoted persister formation in vitro and in vivo. Multiomics analysis identified molecular changes in S. aureus in response to acid stress leading to an overall virulent population. However, further analysis of a persister-enriched population revealed major molecular reprogramming in persisters, including down-regulation of virulence and cell division and up-regulation of ribosomal proteins, nucleotide-, and amino acid-metabolic pathways, suggesting their requirement to fuel and maintain the persister phenotype and highlighting that persisters are not completely metabolically inactive. Additionally, decreased aconitase activity and ATP levels and accumulation of insoluble proteins involved in transcription, translation, and energy production correlated with persistence in S. aureus, underpinning the molecular mechanisms that drive the persister phenotype. Upon regrowth, these persisters regained their virulence potential and metabolically active phenotype, including reduction of insoluble proteins, exhibiting a reversible state, crucial for recurrent infections. We further show that a targeted antipersister combination therapy using retinoid derivatives and antibiotics significantly reduced lag-phase heterogeneity and persisters in a murine infection model. Our results provide molecular insights into persisters and help explain why persistent S. aureus infections are so difficult to treat.

Impact of sex and gender on post-COVID-19 syndrome, Switzerland, 2020.

BackgroundWomen are overrepresented among individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown.AimWe assessed the impact of sex and gender on PASC in a Swiss population.MethodOur multicentre prospective cohort study included 2,856 (46% women, mean age 44.2 ± 16.8 years) outpatients and hospitalised patients with PCR-confirmed SARS-CoV-2 infection.ResultsAmong those who remained outpatients during their first infection, women reported persisting symptoms more often than men (40.5% vs 25.5% of men; p < 0.001). This sex difference was absent in hospitalised patients. In a crude analysis, both female biological sex (RR = 1.59; 95% CI: 1.41-1.79; p < 0.001) and a score summarising gendered sociocultural variables (RR = 1.05; 95% CI: 1.03-1.07; p < 0.001) were significantly associated with PASC. Following multivariable adjustment, biological female sex (RR = 0.96; 95% CI: 0.74-1.25; p = 0.763) was outperformed by feminine gender-related factors such as a higher stress level (RR = 1.04; 95% CI: 1.01-1.06; p = 0.003), lower education (RR = 1.16; 95% CI: 1.03-1.30; p = 0.011), being female and living alone (RR = 1.91; 95% CI: 1.29-2.83; p = 0.001) or being male and earning the highest income in the household (RR = 0.76; 95% CI: 0.60-0.97; p = 0.030).ConclusionSpecific sociocultural parameters that differ in prevalence between women and men, or imply a unique risk for women, are predictors of PASC and may explain, at least in part, the higher incidence of PASC in women. Once patients are hospitalised during acute infection, sex differences in PASC are no longer evident.

Antibody response to a third SARS-CoV-2 vaccine dose in recipients of an allogeneic haematopoietic cell transplantation.

Allogeneic haematopoietic cell transplantation (allo-HCT) recipients show impaired antibody (Ab) response to a standard two-dose vaccination against severe acute respiratory syndrome coronavirus-2 and currently a third dose is recommended as part of the primary vaccination regimen. By assessing Ab titres 1 month after a third mRNA vaccine dose in 74 allo-HCT recipients we show sufficient neutralisation activity in 77% of the patients. Discontinuation of immunosuppression before the third vaccine led to serological responses in 50% of low responders to two vaccinations. Identifying factors that might contribute to better vaccine responses in allo-HCT recipients is critical to optimise current vaccination strategies.

Antibiotic prophylaxis before dental procedures to prevent infective endocarditis: a systematic review.

PURPOSE: Infective endocarditis (IE) is a severe bacterial infection. As a measure of prevention, the administration of antibiotic prophylaxis (AP) prior to dental procedures was recommended in the past. However, between 2007 and 2009, guidelines for IE prophylaxis changed all around the word, limiting or supporting the complete cessation of AP. It remains unclear whether AP is effective or not against IE. METHODS: We conducted a systematic review whether the administration of AP in adults before any dental procedure, compared to the non-administration of such drugs, has an effect on the risk of developing IE. We searched for studies in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via OVID, and EMBASE. Two different authors filtered articles independently and data extraction was performed based on a pre-defined protocol. RESULTS: The only cohort study meeting our criteria included patients at high-risk of IE. Analysis of the extracted data showed a non-significant decrease in the risk of IE when high-risk patients take AP prior to invasive dental procedures (RR 0.39, p-value 0.11). We did not find other studies including patients at low or moderate risk of IE. Qualitative evaluation of the excluded articles reveals diversity of results and suggests that most of the state-of-the-art articles are underpowered. CONCLUSIONS: Evidence to support or discourage the use of AP prior to dental procedures as a prevention for IE is very low. New high-quality studies are needed, even though such studies would require big settings and might not be immediately feasible.

Assessing Antibiotic Tolerance of Staphylococcus aureus Derived Directly from Patients by the Replica Plating Tolerance Isolation System (REPTIS).

Antibiotic-tolerant Staphylococcus aureus poses a great challenge to clinicians as well as to microbiological laboratories and is one reason for treatment failure. Antibiotic-tolerant strains survive transient antibiotic exposure despite being fully susceptible in vitro. Thus, fast and reliable methods to detect tolerance in the routine microbiology laboratory are urgently required. We therefore evaluated the feasibility of the replica plating tolerance isolation system (REPTIS) to detect antibiotic tolerance in Staphylococcus aureus isolates derived directly from patients suffering from different types of infections and investigated possible connections to clinical presentations and patient characteristics. One hundred twenty-five S. aureus isolates were included. Replica plating of the original resistance testing plate was used to assess regrowth in the zones of inhibition, indicating antibiotic tolerance. Bacterial regrowth was assessed after 24 and 48 h of incubation, and an overall regrowth score (ORS) was assigned. Regrowth scores were compared to the clinical presentation. Bacterial regrowth was high for most antibiotics targeting protein synthesis and relatively low for antibiotics targeting other cellular functions such as DNA replication, transcription, and cell wall synthesis, with the exception of rifampin. Isolates with a blaZ penicillinase had lower regrowth in penicillin and ampicillin. Low ORSs were more prevalent among isolates recovered from patients with immunosuppression or methicillin-resistant S. aureus (MRSA) isolates. In conclusion, REPTIS is useful to detect antibiotic tolerance in clinical microbiological routine diagnostics. Further studies should evaluate the impact of rapid detection of antibiotic tolerance as a clinical decision-making tool for tailored antibiotic treatments.

Antibiotic resistance and persistence-Implications for human health and treatment perspectives.

Antimicrobial resistance (AMR) and persistence are associated with an elevated risk of treatment failure and relapsing infections. They are thus important drivers of increased morbidity and mortality rates resulting in growing healthcare costs. Antibiotic resistance is readily identifiable with standard microbiological assays, and the threat imposed by antibiotic resistance has been well recognized. Measures aiming to reduce resistance development and spreading of resistant bacteria are being enforced. However, the phenomenon of bacteria surviving antibiotic exposure despite being fully susceptible, so-called antibiotic persistence, is still largely underestimated. In contrast to antibiotic resistance, antibiotic persistence is difficult to measure and therefore often missed, potentially leading to treatment failures. In this review, we focus on bacterial mechanisms allowing evasion of antibiotic killing and discuss their implications on human health. We describe the relationship between antibiotic persistence and bacterial heterogeneity and discuss recent studies that link bacterial persistence and tolerance with the evolution of antibiotic resistance. Finally, we review persister detection methods, novel strategies aiming at eradicating bacterial persisters and the latest advances in the development of new antibiotics.

The importance of intravenous immunoglobulin treatment in critically ill patients with necrotizing soft tissue infection: a retrospective cohort study.

BACKGROUND: Necrotizing soft-tissue infections are infections with high mortality. The use of immunoglobulins within a combination therapy including broad-spectrum antibiotics has been debated. We assessed potential benefits of immunoglobulins and hypothesized that they were associated with a treatment benefit in a high-resource setting. METHODS: Patients with necrotizing soft-tissue infection hospitalized in the tertiary intensive care unit of the University Hospital of Zurich, Switzerland, between 2008 and 2020 were included retrospectively. The association between immunoglobulin administration and in-hospital survival, intensive care unit length of stay, the incidences of acute renal failure, acute respiratory distress syndrome and septic shock were analyzed. RESULTS: After adjustment for confounders, no difference for in-hospital survival (hazard ratio 2.20, 95% confidence interval [CI] 0.24-20.20, p = 0.5), intensive care unit length of stay (subhazard ratio [SHR] 0.90, CI 0.41-1.98, p = 0.8) and the development of acute respiratory distress syndrome (SHR 1.2, CI 0.36-4.03, p = 0.77) was observed in patients with or without immunoglobulin treatment. The Simplified Acute Physiology Score II, the risk of developing acute renal failure (SHR 2.86, CI 1.33-6.15, p = 0.01) and septic shock (SHR 1.86, CI 1.02-3.40, p = 0.04) was higher in patients treated with immunoglobulins, possibly reflecting a higher disease severity beyond measured confounders. CONCLUSIONS: No clear evidence for a benefit of immunoglobulins in our cohort with consistent antibiotic use was found. Patients receiving immunoglobulins appeared more severely ill. Complementary to high treatment standards and appropriate antibiotics including beta lactams and protein synthesis inhibitors, immunoglobulins should be administered on a case-to-case basis, at least while more evidence from larger randomized controlled trials is missing.

Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19.

BACKGROUND: Whereas severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody tests are increasingly being used to estimate the prevalence of SARS-CoV-2 infection, the determinants of these antibody responses remain unclear. OBJECTIVES: Our aim was to evaluate systemic and mucosal antibody responses toward SARS-CoV-2 in mild versus severe coronavirus disease 2019 (COVID-19) cases. METHODS: Using immunoassays specific for SARS-CoV-2 spike proteins, we determined SARS-CoV-2-specific IgA and IgG in sera and mucosal fluids of 2 cohorts, including SARS-CoV-2 PCR-positive patients (n = 64) and PCR-positive and PCR-negtive health care workers (n = 109). RESULTS: SARS-CoV-2-specific serum IgA titers in patients with mild COVID-19 were often transiently positive, whereas serum IgG titers remained negative or became positive 12 to 14 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2-specific serum IgA and IgG titers after symptom onset. Very high titers of SARS-CoV-2-specific serum IgA were correlated with severe acute respiratory distress syndrome. Interestingly, some health care workers with negative SARS-CoV-2-specific serum antibody titers showed SARS-CoV-2-specific IgA in mucosal fluids with virus-neutralizing capacity in some cases. SARS-CoV-2-specific IgA titers in nasal fluids were inversely correlated with age. CONCLUSIONS: Systemic antibody production against SARS-CoV-2 develops mainly in patients with severe COVID-19, with very high IgA titers seen in patients with severe acute respiratory distress syndrome, whereas mild disease may be associated with transient production of SARS-CoV-2-specific antibodies but may stimulate mucosal SARS-CoV-2-specific IgA secretion.

Factors affecting outcome in the treatment of streptococcal periprosthetic joint infections: results from a single-centre retrospective cohort study.

PURPOSE: To report and analyse factors affecting the outcome of streptococcal periprosthetic joint infections (PJIs). METHODS: A retrospective analysis of consecutive streptococcal PJIs was performed. Musculoskeletal Infection Society 2013 criteria were used. Outcome was compared with a prospective PJI cohort from the same institution. RESULTS: The most common isolated streptococcal species was Streptococcus dysgalactiae (9/22, 41%) among 22 patients included. Surgical treatment consisted of DAIR (debridement, antibiotics, irrigation and retention) in 12 (55%), one-stage revision arthroplasty in one (4%), two-stage revision arthroplasty in eight (37%) and implant removal in one (4%) patient. An infection free-outcome was achieved in 15 cases (68%), whilst seven (32%) patients failed initial revision and relapsed with the same pathogen, from which six were treated with DAIR and one with one-stage revision arthroplasty. No failures were observed in patients who received a two-stage revision. Failure rates did not differ in the cases treated with rifampin (1/5) from those without 6/17 (p = 0.55). There was no correlation between the length of antibiotic treatment and relapse (p = 0.723). In all failures, a persistent distant infection focus was identified at the time of relapse. Compared with our prospective PJI cohort, relapse rates were significantly higher 32% vs 12% (p < 0.05). CONCLUSION: No correlation with the use of rifampin or length of antibiotic treatment was found. No failures were observed in patients who received a two-stage revision, which may be the surgical treatment of choice. A distant persisting infection focus could be the reason for PJI relapse with recurrent hematogenous seeding in the joint.

Polyester Vascular Graft Material and Risk for Intracavitary Thoracic Vascular Graft Infection1.

Prosthetic vascular graft infections of the thoracic aorta are rare but can be fatal. Our comparison of collagen- and gelatin-coated grafts showed that collagen-coated grafts were associated with increased biofilm formation and bacterial adherence in vitro and with higher rates of perioperative vascular graft infections in vivo.

Antibiotics Stimulate Formation of Vesicles in Staphylococcus aureus in both Phage-Dependent and -Independent Fashions and via Different Routes.

Bacterial membrane vesicle research has so far focused mainly on Gram-negative bacteria. Only recently have Gram-positive bacteria been demonstrated to produce and release extracellular membrane vesicles (MVs) that contribute to bacterial virulence. Although treatment of bacteria with antibiotics is a well-established trigger of bacterial MV formation, the underlying mechanisms are poorly understood. In this study, we show that antibiotics can induce MVs through different routes in the important human pathogen Staphylococcus aureus DNA-damaging agents and antibiotics inducing the SOS response triggered vesicle formation in lysogenic strains of S. aureus but not in their phage-devoid counterparts. The ß-lactam antibiotics flucloxacillin and ceftaroline increased vesicle formation in a prophage-independent manner by weakening the peptidoglycan layer. We present evidence that the amount of DNA associated with MVs formed by phage lysis is greater than that for MVs formed by ß-lactam antibiotic-induced blebbing. The purified MVs derived from S. aureus protected the bacteria from challenge with daptomycin, a membrane-targeting antibiotic, both in vitro and ex vivo in whole blood. In addition, the MVs protected S. aureus from killing in whole blood, indicating that antibiotic-induced MVs function as a decoy and thereby contribute to the survival of the bacterium.

Human Streptococcal Necrotizing Fasciitis Histopathology Mirrored in a Murine Model.

Streptococcal necrotizing fasciitis (NF) causes high morbidity and mortality despite state-of-the-art therapy. Low incidence and rapid disease progression, necessitating immediate initiation of therapy, have proven challenging aspects for setting up prospective randomized trials. This has resulted in little therapeutic progress over the past decade. The validation of reliable murine NF models to study both pathogenesis and optimized therapeutic regimens of streptococcal NF are thus essential. In this study, we characterized a murine NF model and compared the pathology with an in-depth tissue analysis of streptococcal NF in patients. We found that the streptococcal murine NF model closely reflected all histologic characteristics encountered in human streptococcal NF. This murine NF model helps understanding of human NF pathology better in a time-dependent manner and will allow studying novel therapeutic options in the future.

Immunoglobulin Attenuates Streptokinase-Mediated Virulence in Streptococcus dysgalactiae Subspecies equisimilis Necrotizing Fasciitis.

Background: Necrotizing fasciitis (NF) retains a very high mortality rate despite prompt and adequate antibiotic treatment and surgical debridement. Necrotizing fasciitis has recently been associated with Streptococcus dysgalactiae subspecies equisimilis (SDSE). Methods: We investigated the causes of a very severe clinical manifestation of SDSE-NF by assessing both host and pathogen factors. Results: We found a lack of streptokinase-function blocking antibodies in the patient resulting in increased streptokinase-mediated fibrinolysis and bacterial spread. At the same time, the clinical SDSE isolate produced very high levels of streptokinase. Exogenous immunoglobulin Gs (ex-IgGs) efficiently blocked streptokinase-mediated fibrinolysis in vitro, indicating a protective role against the action of streptokinase. In vivo, SDSE infection severity was also attenuated by ex-IgGs in a NF mouse model. Conclusions: These findings illustrate for the first time that the lack of specific antibodies against streptococcal virulence factors, such as streptokinase, may contribute to NF disease severity. This can be counteracted by ex-IgGs.

Propionibacterium avidum: A Virulent Pathogen Causing Hip Periprosthetic Joint Infection.

Background: Propionibacteria are important members of the human skin microbiota, but are also opportunistic pathogens associated with periprosthetic joint infection (PJI). While the role of Propionibacterium acnes in PJI has been widely described, insight into the capacity of Propionibacterium avidum to cause PJI is limited. Methods: An unusual cluster of 4 hip PJIs caused by P. avidum in one orthopedic center in 2015 prompted us to retrospectively identify and analyze clinical data related to previous P. avidum PJI cases (1997-2015). We also characterized the hemolytic and biofilm-producing capacity of our 4 clinical P. avidum strains isolated in 2015, and investigated their phylogenetic relationships by whole-genome sequencing. Results: We retrospectively identified 13 P. avidum PJIs, with the majority being hip-related infections (n = 11). Preoperative synovial fluid cultures were P. avidum positive in 63.6% of cases. Six of 12 patients (50%) with available case histories were treated with an exchange of the prosthesis. In all but 1 of the 6 patients treated with debridement-retention of the prosthesis, treatment failed, thus requiring a 2-stage revision. The isolated P. avidum strains showed a more pronounced hemolytic activity, but a similar biofilm-forming ability when compared to P. acnes. Whole-genome sequencing identified 2 phylogenetic clusters highly related to P. avidum PJI strains isolated in Sweden. Conclusions: We describe the largest series of P. avidum PJI predominantly located in the hip. Phylogenetic similarity of our P. avidum strains to PJI strains isolated elsewhere suggests that these invasive lineages may be common.

Perioperative Antibiotic Prophylaxis Has No Effect on Time to Positivity and Proportion of Positive Samples: a Cohort Study of 64 Cutibacterium acnes Bone and Joint Infections.

If a bone or joint infection is suspected, perioperative antibiotic prophylaxis is frequently withheld until intraoperative microbiological sampling has been performed. This practice builds upon the hypothesis that perioperative antibiotics could render culture results negative and thus impede tailored antibiotic treatment of infections. We aimed to assess the influence of antibiotic prophylaxis within 30 to 60 min before surgery on time to positivity of microbiological samples and on proportion of positive samples in Cutibacterium acnes bone and joint infections. Patients with at least one sample positive for C. acnes between January 2005 and December 2015 were included and classified as having an "infection" if at least 2 samples were positive; otherwise they were considered to have a sample "contamination." Kaplan-Meier curves were used to illustrate time to culture positivity. We found 64 cases with a C. acnes infection and 46 classified as having a C. acnes contamination. Application of perioperative prophylaxis significantly differed between the infection and contamination groups (72.8% versus 55.8%; P < 0.001). Within the infection group, we found no difference in time to positivity between those who had or had not received a perioperative prophylaxis (7.07 days; 95% confidence interval [CI], 6.4 to 7.7, versus 7.11 days; 95% CI, 6.8 to 7.5; P = 0.3). Also, there was no association between the proportion of sample positivity and the application of perioperative prophylaxis (71.6% versus 65.9%; P = 0.39). Since perioperative prophylaxis did not negatively influence the microbiological yield in C. acnes infections, antibiotic prophylaxis can be routinely given to avoid surgical site infections.

Corynebacterium Species Rarely Cause Orthopedic Infections.

Corynebacterium spp. are rarely considered pathogens, but data on Corynebacterium spp. as a cause of orthopedic infections are sparse. Therefore, we asked how often Corynebacterium spp. caused an infection in a defined cohort of orthopedic patients with a positive culture. In addition, we aimed to determine the species variety and the susceptibility of isolated strains to define potential treatment strategies. We retrospectively assessed all bone and joint samples that were collected between 2006 and 2015 from an orthopedic ward and that were positive for Corynebacterium spp. by culture. The isolates were considered relevant to an infection if the same Corynebacterium sp. was present in at least two samples. We found 97 orthopedic cases with isolation of Corynebacterium spp. (128 positive samples). These were mainly Corynebacterium tuberculostearicum (n = 26), Corynebacterium amycolatum (n = 17), Corynebacterium striatum (n = 13), and Corynebacterium afermentans (n = 11). Compared to the species found in a cohort of patients with positive blood cultures hospitalized in nonorthopedic wards, we found significantly more C. striatum- and C. tuberculostearicum-positive cases but no C. jeikeium-positive cases in our orthopedic cohort. Only 16 out of 66 cases (24.2%) with an available diagnostic set of at least two samples had an infection. Antibiotic susceptibility testing (AST) showed various susceptibility results for all antibiotics except vancomycin and linezolid, to which 100% of the isolates were susceptible. The rates of susceptibility of corynebacteria isolated from orthopedic samples and of isolates from blood cultures were comparable. In conclusion, our study results confirmed that a Corynebacterium sp. is most often isolated as a contaminant in a cohort of orthopedic patients. AST is necessary to define the optimal treatment in orthopedic infections.