Systemic Inflammation Response Index (SIRI) and Monocyte-to-Lymphocyte Ratio (MLR) Are Predictors of Good Outcomes in Surgical Treatment of Periprosthetic Joint Infections of Lower Limbs: A Single-Center Retrospective Analysis.

BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication that develops after total joint arthroplasty (TJA), whose incidence is expected to increase over the years. Traditionally, surgical treatment of PJI has been based on algorithms, where early infections are preferably treated with debridement, antibiotics, and implant retention (DAIR) and late infections with two-stage revision surgery. Two-stage revision is considered the "gold standard" for treatment of chronic prosthetic joint infection (PJI) as it enables local delivery of antibiotics, maintenance of limb-length and mobility, and easier reimplantation. Many studies have attempted to identify potential predicting factors for early diagnosis of PJI, but its management remains challenging. In this observational retrospective study, we investigated the potential role of inflammatory blood markers (neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory index (SII), systemic inflammatory response index (SIRI), and aggregate index of systemic inflammation (AISI)) as prognostic factors in two-stage exchange arthroplasty for PJI. METHODS: A single-center retrospective analysis was conducted, collecting clinical data and laboratory parameters from patients submitted to prosthetic explantation (EP) for chronic PJI. Laboratory parameters (PCR, NLR, MLR, PLR, SIRI, SII, and AISI) were evaluated at the explantation time; at 4, 6, and 8 weeks after surgery; and at reimplantation time. The correlation between laboratory parameters and surgery success was evaluated and defined as infection absence/resolution at the last follow-up. RESULTS: A total of 57 patients with PJI were evaluated (62% males; average age 70 years, SD 12.14). Fifty-three patients with chronic PJI were included. Nine patients underwent DAIR revision surgery and chronic suppressive therapy; two patients died. Nineteen patients completed the two-stage revision process (prosthetic removal, spacer placement, and subsequent replanting). Among them, none showed signs of reinfection or persistence of infection at the last available follow-up. The other twenty-three patients did not replant due to persistent infection: among them, some (the most) underwent spacer retention; others (fewer in number) were submitted to resection arthroplasty and arthrodesis (Girdlestone technique) or chronic suppressive antibiotic therapy; the remaining were, over time, lost to follow-up. Of the patients who concluded the two-stage revision, the ones with high SIRI values (mean 3.08 SD 1.7 and p-value 0.04) and MLR values (mean 0.4 SD 0.2 and p-value 0.02) at the explantation time were associated with a higher probability of infection resolution. Moreover, higher variation in the SIRI and PCR, also defined, respectively, as delta-SIRI (mean -2.3 SD 1.8 and p-value 0.03) and delta-PCR (mean -46 SD 35.7 and p-value 0.03), were associated with favorable outcomes. CONCLUSIONS: The results of our study suggest that, in patients with PJI undergoing EP, the SIRI and MLR values and delta-SIRI and delta-PCR values could be predictive of a favorable outcome. The evaluation of these laboratory indices, especially their determination at 4 weeks after removal, could therefore help to determine which patients could be successfully replanted and to identify the best time to replant. More studies analyzing a wider cohort of patients with chronic PJI are needed to validate the promising results of this study.

Cerebrospinal fluid drain infection caused by pandrug-resistant Staphylococcus epidermidis successfully treated with ceftaroline in combination with fosfomycin and vancomycin.

External ventricular drain-related cerebrospinal fluid infection represents a fearsome complication of neurosurgical interventions. Although vancomycin represents the standard of care for methicillin-resistant CoNS healthcare-associated ventriculitis, resistance phenomena have been described. We reported a case of a persistent external ventricular fluid drain infection after device removal by pandrug-resistant Staphylococcus epidermidis successfully treated with intravenous ceftaroline in combination with fosfomycin and vancomycin. No evidence regarding pandrug-resistant S. epidermidis therapy currently exists to our knowledge. In this case, the S. epidermidis phenotype emerged during the therapy course, possibly due to initial device retention, biofilm formation and the host immune impaired response. Despite being poorly studied in vivo, ceftaroline may be considered an option when other alternatives are unavailable, thanks to its described activity against CoNS in vitro. This case extends the experience with ceftaroline for central nervous system infections suggesting it could also be used in high antimicrobial resistance settings for immunocompromised people.

A 67-Year-Old Man with Chronic Lymphocytic Leukemia (CLL) on Maintenance Therapy with Ibrutinib with Persistent SARS-CoV-2 Infection Unresponsive to Antiviral Treatments.

BACKGROUND SARS-CoV-2 infection can persist in immunocompromised patients with hematological malignancies, despite antiviral treatment. This report is of a 67-year-old man with chronic lymphocytic leukemia (CLL), secondary hypogammaglobulinemia, and thrombocytopenia on maintenance therapy with ibrutinib, with persistent SARS-CoV-2 infection unresponsive to antiviral treatment, including remdesivir, nirmatrelvir/ritonavir (Paxlovid), and tixagevimab/cilgavimab (Evusheld). CASE REPORT The patient was admitted to our hospital 3 times. During his first hospitalization, he was treated with 5-day course of remdesivir and intravenous steroids; however, antigen and molecular nasopharyngeal swabs were persistently positive, and he was discharged home. Due to respiratory worsening, he was rehospitalized, and despite being treated initially with tixagevimab/cilgavimab, and subsequently with a remdesivir course of 5 days, SARS-CoV-2 tests remained persistently positive. During his third hospital stay, our patient was subjected to combined therapy with remdesivir and nirmatrelvir/ritonavir for 5 days, obtaining a significant reduction of viral load at both antigen and molecular testing. As an ultimate attempt to achieve a negative status before discharge, a 10-day course of combined remdesivir and nirmatrelvir/ritonavir was administered, with a temporary reduction of viral load, followed by a sudden increase immediately after the discontinuation of Paxlovid. Due to worsening hematological disease and bacterial over-infections, the patient gradually worsened until death. CONCLUSIONS This is an emblematic case of correlation between persistent SARS-CoV-2 infection and immunosuppression status in hematological hosts. In these patients, the viral load remains high, favoring the evolution of the virus, and the immunodeficiency makes it difficult to identify the appropriate therapeutic approach.

Gram-negative infections in frail patients.

Introduction: Gram-negative infections (GNIs) are frequently encountered both in community and hospital settings. Frail patients, defined as elderly individuals with multiple comorbidities, are particularly vulnerable to them. The presentation and the course of GNIs differ in aged patients compared with younger ones, making their management a unique challenge. This review aimed to outline the essential elements of the presentation, diagnosis, and outcome of GNIs in frail individuals. Methods: MEDLINE/PubMed library search was performed using the following terms: frail, frailty, elderly, Gram-negative, infections, pneumonia, urinary tract infection, and bloodstream infection for the purpose of the review. Conclusions: Elderly patients with multimorbidity represent a distinct population with relevant differences in GNIs presentation, diagnosis, and outcome. Several pitfalls should be avoided and appropriately addressed when facing GNIs in this group of patients. Future studies focusing on this population should be encouraged.