Ceftriaxone-resistant viridans streptococci bacteraemia among patients treated at a large comprehensive cancer care centre: a retrospective eighteen-year study.

Objectives: Viridans streptococci (VS) are opportunistic oral commensals and a common cause of bacteraemia in neutropenic patients. In this retrospective single centre cohort study, we investigated the prevalence of ceftriaxone resistance in VS (CRO-R VS) blood isolates between January 2005 and December 2022 from patients treated at a tertiary care hospital. Methods: Blood culture isolates were identified using biochemicals and mass spectrometry. Susceptibility testing was performed by Kirby-Bauer and Epsilometer tests. Demographic data, clinical outcomes and antimicrobial use were assessed through electronic medical record review. Results: Among 791 patients with VS bacteraemia, 31 (4%) had confirmed CRO-R VS bacteraemia over the 18-year period; 20/31 (65%) were patients also treated at the Fred Hutchinson Cancer Center and were the focus of this study. Of these 20 patients, 18 (90%) had a known haematologic malignancy; 14 (70%) had undergone haematopoietic cell transplant (HCT); 18 (90%) were neutropenic at the time of culture. Two (10%) patients died within 30 days of CRO-R VS bacteraemia. All the CRO-R isolates (20/20) were members of the Streptococcus mitis group, 12 were multi-drug resistant; all were susceptible to vancomycin. Most patients received vancomycin once blood cultures were positive for a Gram-positive organism. Conclusions: During the study period, the frequency of VS isolate susceptibility testing increased; however, there was no concomitant increase in the percentage of CRO-R isolates at our facility. These data are important in an era where cefepime monotherapy is often used and reinforces the importance of routine resistance testing among VS bacteraemia.

2023 Neer Award for Basic Science: Genetics of Cutibacterium acnes in revision shoulder arthroplasty: a large-scale bacterial whole-genome sequencing study.

BACKGROUND: Cutibacterium acnes is the bacterium most commonly responsible for shoulder periprosthetic joint infection (PJI) and is often cultured from samples obtained at the time of revision for failed shoulder arthroplasty. We sought to determine whether these bacteria originate from the patient or from exogenous sources. We also sought to identify which C. acnes genetic traits were associated with the development of shoulder PJI. METHODS: We performed bacterial whole-genome sequencing of C. acnes from a single-institution repository of cultures obtained before or during primary and revision shoulder arthroplasty and correlated the molecular epidemiology and genetic content of strains with clinical features of infection. RESULTS: A total of 341 isolates collected over a 4-year period from 88 patients were sequenced. C. acnes cultured from surgical specimens demonstrated significant similarity to the strains colonizing the skin of the same patient (P < .001). Infrequently, there was evidence of strains shared across unrelated patients, suggesting that exogenous sources of C. acnes culture-positivity were uncommon. Phylotypes IB and II were modestly associated with clinical features of PJI, but all phylotypes appeared inherently capable of causing disease. Chronic shoulder PJI was associated with the absence of common C. acnes genes involved in bacterial quorum-sensing (luxS, tqsA). CONCLUSION: C. acnes strains cultured from deep intraoperative sources during revision shoulder arthroplasty demonstrate strong genetic similarity to the strains colonizing a patient's skin. Some phylotypes of C. acnes commonly colonizing human skin are modestly more virulent than others, but all phylotypes have a capacity for PJI. C. acnes cultured from cases of PJI commonly demonstrated genetic hallmarks associated with adaptation from acute to chronic phases of infection. This is the strongest evidence to date supporting the role of the patient's own, cutaneous C. acnes strains in the pathogenesis of shoulder arthroplasty infection. Our findings support the importance of further research focused on perioperative decolonization and management of endogenous bacteria that are likely to be introduced into the arthroplasty wound at the time of skin incision.

What do positive and negative Cutibacterium culture results in periprosthetic shoulder infection mean? A multi-institutional control study.

BACKGROUND: Deep tissue culture specimens obtained at the time of revision shoulder arthroplasty are commonly positive for Cutibacterium. Clinical interpretation of positive cultures can be difficult. This was a multi-institutional study evaluating the accuracy of cultures for Cutibacterium using positive control (PC) and negative control (NC) samples. The relationship between time to culture positivity and strength of culture positivity was also studied. METHODS: Eleven different institutions were each sent 12 blinded samples (10 PC and 2 NC samples). The 10 PC samples included 2 sets of 5 different dilutions of a Cutibacterium isolate from a failed total shoulder arthroplasty with a probable periprosthetic infection. At each institution, the samples were handled as if they were received from the operating room. Specimen growth, time to culture positivity, and strength of culture positivity (based on semiquantitative assessment) were reported. RESULTS: A total of 110 PC samples and 22 NC samples were tested. One hundred percent of specimens at the 4 highest dilutions were positive for Cutibacterium. At the lowest dilution, 91% of samples showed positive findings. Cutibacterium grew in 14% of NC samples. Cutibacterium grew in PC samples at an average of 4.0 ± 1.3 days, and all of these samples showed growth within 7 days. The time to positivity was significantly shorter (P < .001) and the strength of positivity was significantly higher (P < .001) in true-positive cultures compared with false-positive cultures. CONCLUSIONS: This multi-institutional study suggests that different institutions may report highly consistent rates of culture positivity for revision shoulder arthroplasty samples with higher bacterial loads. In contrast, with lower bacterial loads, the results are somewhat less consistent. Clinicians should consider using a shorter time to positivity and a higher strength of positivity as adjuncts in determining whether a tissue culture sample is a true positive.

Treatment of Granulomatous Mastitis: Is There a Role for Antibiotics?

OBJECTIVE: To perform a retrospective review of the clinical characteristics, microbiological data, and clinical outcomes in patients with granulomatous mastitis (GM) who were treated at our institution with a unique strategy of prolonged antibiotic therapy as the primary treatment modality. MATERIALS AND METHODS: A retrospective case series was performed on patients (n = 42) with GM seen at the breast specialty clinic of our institution between the years 2004 and 2014. Patients were primarily treated with lipophilic antibiotics, and steroids and surgery were reserved for refractory cases. RESULTS: Bacteria were identified in 34 samples from 22/42 patients (52.3%). Diphtheroids (presumptive Corynebacterium spp.) were most commonly identified, followed by Corynebacterium spp. and Propionibacterium acnes (now Cutibacterium acnes). Antibiotics were our preferred first-line medical therapy and were used in 33/36 (91.7%) patients. The mean duration of antibiotic therapy was 7.0±4.5 months. Clarithromycin was our antibiotic of choice and was the initial antibiotic used in 15 of the 33 patients (45.5%) treated with antibiotics. Eleven patients required adjunctive therapy with prednisone. The mean duration of steroid therapy was 4.3±2.5 months. Surgery for therapeutic purposes included incision and drainage in seven patients, fine needle aspiration in eight patients, and excision of the fistulous tract in one patient. No patients had large-volume excisions. The average time from the first breast clinic visit to clinical resolution was 8.0±4.6 months. CONCLUSION: GM may be the result of a bacterial process that induces a unique form of inflammatory response. Clinicians should consider special requests to microbiology laboratories to attempt to isolate Corynebacterium spp. in the evaluation of samples sent to the laboratory for analysis. An extended course of a lipophilic antibiotic is a largely unexplored but potentially effective treatment option with low associated morbidity. More research is needed in this area.

Long-Term Carriage of Medicopsis romeroi, an Agent of Black-Grain Mycetoma, Presenting as Phaeohyphomycosis in a Renal Transplant Patient.

Medicopsis species are rare fungal pathogens that frequently resist common antifungal therapies and are difficult to identify morphologically as conidia are produced in pycnidia, a key feature of coelomycetes. Immunocompromised patients are at risk of these infections, even after remote exposure, and typically present with phaeohyphomycoses without dissemination. We present the case of a renal transplant recipient 6.5 years post-transplant who developed a slowly progressive soft tissue infection mimicking a synovial cyst. A cultured isolate was identified as Medicopsis romeroi by sequencing of multiple ribosomal loci. The patient responded well to debridement and posaconazole therapy. Solid-organ transplant patients are at risk of opportunistic fungal infection long after transplant, and molecular methods are often required for definitive identification.

Limited Utility of Outpatient Surveillance Blood Cultures in Hematopoietic Cell Transplant Recipients on High-Dose Steroids for Treatment of Acute Graft-versus-Host-Disease.

Steroids used to treat acute graft-versus-host-disease (GVHD) are believed to blunt clinical symptoms of infection. We aimed to assess the value of weekly surveillance blood cultures (SBCs) drawn in an outpatient setting from hematopoietic cell transplant (HCT) patients receiving high-dose steroids. We hypothesized that most positive outpatient surveillance cultures would be low-pathogenicity, gram-positive organisms and would lead to excess vancomycin therapy. We conducted a retrospective review of blood cultures collected from a cohort of adult HCT patients enrolled in a clinical trial of acute GVHD therapy with high-dose steroids (prednisone-equivalent doses ≥ .5 mg/kg/day) between April 2009 and May 2013. SBCs were defined as those collected weekly from central venous catheters in the outpatient setting while patients were receiving high-dose steroids. Cultures obtained as part of a symptom workup or as follow-up for documented bacteremia were excluded. Clinical data were collected using center databases supplemented by medical record review. One hundred twenty-seven HCT recipients were eligible for inclusion in the study. A total of 1015 SBCs were obtained, with a median of 8 cultures (interquartile range, 5 to 10) per patient. Forty-two organisms were isolated from 36 of 1015 cultures (3.5%) in 30 unique patients, or 1 positive culture per 28 blood cultures drawn. The most frequently detected organisms were coagulase-negative Staphylococci (25/1015 [2.5%]). Gram-negative organisms were rare (4/1015 [.4%]. Antibiotics were administered to most patients with positive surveillance cultures (33/36 [92%]). Six were admitted to the hospital for treatment; none needed intensive care or died from their bacteremia. Vancomycin was the most frequently administered antibiotic, comprising 256 of 376 total days (68%) of antibiotic received by the cohort with a median duration of 10 days ((interquartile range, 7 to 14). Weekly outpatient SBCs obtained from asymptomatic patients on high-dose glucocorticoids for treatment of acute GVHD after allogeneic HCT were infrequently positive, and most organisms were low-pathogenicity organisms. SBCs also led to excess antibiotic exposure and costs, suggesting benefits of such ambulatory screening may be of limited value in this setting.