Role of Routine Suppressive Antibiotic Therapy After Debridement, Antibiotics, and Implant Retention for Acute Periprosthetic Joint Infections.

Background: The first-line management strategy for acute periprosthetic joint infections (PJIs) is debridement, antibiotics, and implant retention (DAIR). Suppressive antibiotic therapy (SAT) after DAIR is proposed to improve outcomes, yet its efficacy remains under scrutiny. Methods: We conducted a multicenter retrospective study in patients with acute PJI of the hip or knee who were treated with DAIR in centers from Europe and the United States. We analyzed the effect of SAT using a Cox model landmarked at 12 weeks. The primary covariate of interest was SAT, which was analyzed as a time-varying covariate. Patients who experienced treatment failure or were lost to follow-up within 12 weeks were excluded from the analysis. Results: The study included 510 patients with 66 treatment failures with a median follow-up of 801 days. We did not find a statistically significant association between SAT and treatment failure (hazard ratio, 1.37; 95% CI, .79-2.39; P = .27). Subgroup analyses for joint, country cohort, and type of infection (early or late acute) did not show benefit for SAT. Secondary analysis of country cohorts showed a trend toward benefit for the US cohort (hazard ratio, 0.36; 95% CI, .11-1.15; P = .09), which also had the highest risk of treatment failure. Conclusions: The utility of routine SAT as a strategy for enhancing DAIR's success in acute PJI remains uncertain. Our results suggest that SAT's benefits might be restricted to specific groups of patients, underscoring the need for randomized controlled trials. Identifying patients most likely to benefit from SAT should be a priority in future studies.

Phage Therapy for Cardiac Implantable Electronic Devices and Vascular Grafts: A Targeted Literature Review.

Infections of cardiac implantable electronic devices (CIEDs) and vascular grafts are some of the most dreaded complications of these otherwise life-saving devices. Many of these infections are not responsive to conventional treatment, such as systemic antibiotics and surgical irrigation and debridement. Therefore, innovative strategies to prevent and manage these conditions are warranted. Among these, there is an increasing interest in phages as a therapeutical option. In this review, we aim to collect the available evidence for the clinical application of phage therapy for CIED and vascular graft infections through literature research. We found 17 studies for a total of 34 patients. Most of the indications were left ventricular assist device (LVAD) (n = 20) and vascular graft infections (n = 7). The bacteria most often encountered were Staphylococcus aureus (n = 18) and Pseudomonas aeruginosa (n = 16). Clinical improvements were observed in 21/34 (61.8%) patients, with microbiological eradication in 18/21 (85.7%) of them. In eight cases, an adverse event related to phage therapy was reported. Phage therapy is a promising option for difficult-to-treat CIED and vascular graft infections by means of an individualized approach. Clinical trials and expanded access programs for compassionate use are needed to further unveil the role of phage therapy in clinical application.

Effect of Preoperative Antibiotic Therapy on Operative Culture Yield for Diagnosis of Native Joint Septic Arthritis.

BACKGROUND: Native joint septic arthritis (NJSA) is definitively diagnosed by a positive Gram stain or culture, along with supportive clinical findings. Preoperative antibiotics are known to alter synovial fluid cell count, Gram stain and culture results and are typically postponed until after arthrocentesis to optimize diagnostic accuracy. However, data on the impact of preoperative antibiotics on operative culture yield for NJSA diagnosis are limited. METHODS: We retrospectively reviewed adult cases of NJSA who underwent surgery at Mayo Clinic facilities from 2012-2021 to analyze the effect of preoperative antibiotics on operative culture yield through a paired analysis of preoperative culture (POC) and operative culture (OC) results using logistic regression and generalized estimating equations. RESULTS: Two hundred ninety-nine patients with NJSA affecting 321 joints were included. Among those receiving preoperative antibiotics, yield significantly decreased from 68.0% at POC to 57.1% at OC (p < .001). In contrast, for patients without preoperative antibiotics there was a non-significant increase in yield from 60.9% at POC to 67.4% at OC (p = 0.244). In a logistic regression model for paired data, preoperative antibiotic exposure was more likely to decrease OC yield compared to non-exposure (OR = 2.12; 95% CI = 1.24-3.64; p = .006). Within the preoperative antibiotic group, additional antibiotic doses and earlier antibiotic initiation were associated with lower OC yield. CONCLUSION: In patients with NJSA, preoperative antibiotic exposure resulted in a significant decrease in microbiologic yield of operative cultures as compared to patients in whom antibiotic therapy was held prior to obtaining operative cultures.

Phage Therapy as a Novel Therapeutic for the Treatment of Bone and Joint Infections.

Solutions for bone and joint infection (BJI) are needed where conventional treatments are inadequate. Bacteriophages (phages) are naturally occurring viruses that infect bacteria and have been harnessed for refractory bone and joint infections (BJI) in many case reports. Here we examine the safety and efficacy of English-language published cases of BJI since 2010 with phage therapy. From 33 reported cases of BJI treated with phage therapy, 29 (87%) achieved microbiological or clinical success, 2 (5.9%) relapsed with the same organisms, and 2 (5.9%) with a different organism. Of these 4 relapses, all but 1 had eventual clinical resolution with additional surgery or phage treatments. Eight out of 33 cases (24%) reported mild, transient adverse events with no serious events reported. Further work is needed to understand the true efficacy of phages and the role of phages in BJI. Opportunities lay ahead for thoughtfully designed clinical trials adapted to individualized therapies.

Defeating the Hidden Foe: Antibiotic Therapy and Clinical Outcomes of Cutibacterium acnes Spinal Implant Infections.

Background: Cutibacterium acnes can cause spinal implant infections. However, little is known about the optimal medical management and outcomes of C. acnes spinal implant infections (CSII). Our study aims to describe the management of patients with CSII and evaluate the clinical outcomes. Methods: We performed a retrospective cohort study of patients aged 18 years or older who underwent spinal fusion surgery with instrumentation between January 1, 2011, and December 31, 2020, and whose intraoperative cultures were positive for C. acnes. The primary outcome was treatment failure based on subsequent recurrence, infection with another organism, or unplanned surgery secondary to infection. Results: There were 55 patients with a median follow-up (interquartile range) of 2 (1.2-2.0) years. Overall, there were 6 treatment failures over 85.8 total person-years, for an annual rate of 7.0% (95% CI, 2.6%-15.2%). Systemic antibiotic treatment was given to 74.5% (n = 41) of patients for a median duration of 352 days. In the subgroup treated with systemic antibiotics, there were 4 treatment failures (annual rate, 6.3%; 95% CI, 1.7%-16.2%), all of which occurred while on antibiotic therapy. Two failures occurred in the subgroup without antibiotic treatment (annual rate, 8.8%; 95% CI, 1.1%-31.8%). Conclusions: Our study found that the estimated annual treatment failure rate was slightly higher among patients who did not receive antibiotics. Of the 6 failures observed, 4 had recurrence of C. acnes either on initial or subsequent treatment failures. More studies are warranted to determine the optimal duration of therapy for CSII.

A Retrospective, Observational Study of 12 Cases of Expanded-Access Customized Phage Therapy: Production, Characteristics, and Clinical Outcomes.

BACKGROUND: Antimicrobial resistance (AMR) is undermining modern medicine, a problem compounded by bacterial adaptation to antibiotic pressures. Phages are viruses that infect bacteria. Their diversity and evolvability offer the prospect of their use as a therapeutic solution. Reported are outcomes of customized phage therapy for patients with difficult-to-treat antimicrobial resistant infections. METHODS: We retrospectively assessed 12 cases of customized phage therapy from a phage production center. Phages were screened, purified, sequenced, characterized, and Food and Drug Administration-approved via the IND (investigational new drug) compassionate-care route. Outcomes were assessed as favorable or unfavorable by microbiologic and clinical standards. Infections were device-related or systemic. Other experiences such as time to treatment, antibiotic synergy, and immune responses were recorded. RESULTS: Fifty requests for phage therapy were received. Customized phages were generated for 12 patients. After treatment, 42% (5/12) of cases showed bacterial eradication and 58% (7/12) showed clinical improvement, with two-thirds of all cases (66%) showing favorable responses. No major adverse reactions were observed. Antibiotic-phage synergy in vitro was observed in most cases. Immunological neutralization of phages was reported in 5 cases. Several cases were complicated by secondary infections. Complete characterization of the phages (morphology, genomics, and activity) and their production (methods, sterility, and endotoxin tests) are reported. CONCLUSIONS: Customized phage production and therapy was safe and yielded favorable clinical or microbiological outcomes in two-thirds of cases. A center or pipeline dedicated to tailoring the phages against a patient's specific AMR bacterial infection may be a viable option where standard treatment has failed.

Chronic Polymicrobial Infectious Melanonychia Striata.

CASE: A 62-year-old man presented with a 10-year history of isolated melanonychia striata of his dominant thumb. Surgical biopsy ruled out subungual melanoma but revealed foreign plant material causing chronic infectious melanonychia from multiple pathogens, including Pseudomonas aeruginosa, Escherichia coli, and Candida spp. After removal of the nail plate and thorough debridement, the melanonychial streak resolved completely at 12 months of follow-up. CONCLUSION: Bacterial infection is a rarely reported cause of melanonychia, and in addition to surgical pathologic specimens, intraoperative fungal and bacterial cultures should always be obtained for accurate diagnosis of melanonychia striata.

Infections in Patients With Left Ventricular Assist Devices: Current State and Future Perspectives.

Mechanical circulatory support is increasingly being used as bridge-to-transplant and destination therapy in patients with advanced heart failure. Technologic improvements have led to increased patient survival and quality of life, but infection remains one of the leading adverse events following ventricular assist device (VAD) implantation. Infections can be classified as VAD-specific, VAD-related, and non-VAD infections. Risk of VAD-specific infections, such as driveline, pump pocket, and pump infections, remains for the duration of implantation. While adverse events are typically most common early (within 90 days of implantation), device-specific infection (primarily driveline) is a notable exception. No diminishment over time is seen, with event rates of 0.16 events per patient-year in both the early and late periods postimplantation. Management of VAD-specific infections requires aggressive treatment and chronic suppressive antimicrobial therapy is indicated when there is concern for seeding of the device. While surgical intervention/hardware removal is often necessary in prosthesis-related infections, this is not so easily accomplished with VADs. This review outlines the current state of infections in patients supported with VAD therapy and discusses future directions, including possibilities with fully implantable devices and novel approaches to treatment.

Sex-specific analysis of clinical features and outcomes in staphylococcal periprosthetic joint infections managed with two-stage exchange arthroplasty.

Background: Differences in susceptibility and response to infection between males and females are well established. Despite this, sex-specific analyses are under-reported in the medical literature, and there is a paucity of literature looking at differences between male and female patients with periprosthetic joint infection (PJI). Whether there are sex-specific differences in presentation, treatment tolerability, and outcomes in PJI has not been widely evaluated. Methods: We undertook a retrospective case-matched analysis of patients with staphylococcal PJI managed with two-stage exchange arthroplasty. To control for differences other than sex which may influence outcome or presentation, males and females were matched for age group, causative organism category (coagulase-negative staphylococci vs. Staphylococcus aureus), and joint involved (hip vs. knee). Results: We identified 156 patients in 78 pairs of males and females who were successfully matched. There were no significant baseline differences by sex, except for greater use of chronic immunosuppression among females (16.4 % vs. 4.1 %; p = 0.012 ). We did not detect any statistically significant differences in outcomes between the two groups. Among the 156 matched patients, 16 recurrent infections occurred during a median follow-up time of 2.9 (IQR 1.5-5.3) years. The 3-year cumulative incidence of relapse was 16.1 % for females, compared with 8.8 % for males ( p = 0.434 ). Conclusions: Success rates for PJI treated with two-stage exchange arthroplasty are high, consistent with previously reported literature. This retrospective case-matched study did not detect a significant difference in outcome between males and females with staphylococcal PJI who underwent two-stage exchange arthroplasty.

Utility of Diagnostic Tests Before Reimplantation in Patients Undergoing 2-Stage Revision Total Joint Arthroplasty: A Systematic Review and Meta-analysis.

INTRODUCTION: Periprosthetic joint infection (PJI) is a devastating complication after total joint arthroplasty (TJA), with treatment failure occurring in 12% to 28% after 2-stage revision. It is vital to identify diagnostic tools indicative of persistent infection or treatment failure after 2-stage revision for PJI. METHODS: The Cochrane Library, PubMed (MEDLINE), and EMBASE were searched for randomized controlled trials and comparative observational studies published before October 3, 2021, which evaluated the utility of serum/plasma biomarkers (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], interleukin-6 [IL-6], fibrinogen, D-dimer), synovial biomarkers (white blood cell [WBC] count, neutrophil percentage [PMN %], alpha-defensin [AD], leukocyte esterase [LE]), tissue frozen section, tissue culture, synovial fluid culture, or sonicated spacer fluid culture indicative of persistent infection before the second stage of 2-stage revision for PJI or treatment failure after 2-stage revision for PJI. RESULTS: A total of 47 studies including 6,605 diagnostic tests among 3,781 2-stage revisions for PJI were analyzed. Among those cases, 723 (19.1%) experienced persistent infection or treatment failure. Synovial LE (sensitivity 0.25 [0.10-0.47], specificity 0.99 [0.93-1.00], positive likelihood ratio 14.0 [1.45-135.58]) and serum IL-6 (sensitivity 0.52 [0.33-0.70], specificity 0.92 [0.85-0.96], positive likelihood ratio 7.90 [0.86-72.61]) had the highest diagnostic accuracy. However, no biomarker was associated with a clinically useful negative likelihood ratio. In subgroup analysis, synovial PMN %, synovial fluid culture, serum ESR, and serum CRP had limited utility for detecting persistent infection before reimplantation (positive likelihood ratios ranging 2.33-3.74; negative likelihood ratios ranging 0.31-0.9) and no utility for predicting failure after the second stage of 2-stage revision. CONCLUSIONS: Synovial WBC count, synovial PMN %, synovial fluid culture, serum ESR, and serum CRP have modest sensitivity and specificity for predicting persistent infection during the second stage of 2-stage revision, suggesting some combination of these diagnostic tests might be useful before reimplantation. No biomarker or culture accurately predicted treatment failure after reimplantation. LEVEL OF EVIDENCE: Level III. See Instructions for Authors for a complete description of levels of evidence.

Chronic Q fever presenting as bilateral extensor tenosynovitis: a case report and review of the literature.

Musculoskeletal manifestations of Coxiella burnetii are rare. We describe an elderly, immunosuppressed male with bilateral Coxiella burnetii extensor tenosynovitis treated with incision and debridement and chronic doxycycline and hydroxychloroquine. Additionally, disease etiology, risk factors, pertinent features of the history, testing modalities, and treatment strategies of musculoskeletal Q fever are reviewed.

Clinical phage microbiology: a narrative summary.

BACKGROUND: Although phage therapy has been in existence for a century, a recent resurgence in interest has occurred because of the continued emergence of antimicrobial resistance and the rising use of indwelling medical devices, resulting in biofilm-associated infections, for which conventional antibiotics are of limited use. Despite this, the clinical successes have been inconsistent because of multiple reasons, including (1) the narrow host range of phages, (2) challenges with concentrating phages at the site of infection, (3) development of resistance of bacteria to phages and (4) immune neutralization. Microbiologic assays have the potential to help guide the course of clinical therapy and improve outcomes. Methods developed decades ago remain the mainstay of phage diagnostics and recently, newer diagnostics are closing the gap needed to further advance clinical phage therapy. OBJECTIVES: To review the current state of clinical phage microbiology and identify gaps. SOURCES: A PubMed search was performed using the terms "phage microbiology", "phage susceptibility test", "phage host range", "phage biofilm", and "phage therapeutic monitoring". CONTENT: Phage susceptibility testing, biofilm assays, phage-antibiotic combination testing, therapeutic drug monitoring, and immune monitoring assays are the current foundation for clinical phage diagnostics. Standardization of these assays and better understanding as to if and how they should be used in terms of clinical management of patients receiving phage therapy is needed. IMPLICATIONS: A substantial gap between in vitro studies and in vivo outcomes indicates that further work is needed in phage pharmacokinetics to accurately assay phage particles at the site of infection; recapitulate in vivo biofilm; capture the complex interactions between phages and antibiotics, phages and their target bacteria, among phages in a cocktail, and with the superhost immune system.

Outcomes and risk factors for failure after débridement, antibiotics, and implant retention for elbow periprosthetic joint infection.

BACKGROUND: Evidence for the management of periprosthetic joint infection (PJI) after total elbow arthroplasty is sparse, particularly in regard to débridement, antibiotics, and implant retention (DAIR). This study explored the outcomes of DAIR and analyzed risk factors for failure. METHODS: A retrospective cohort study of patients 18 years or older diagnosed with elbow PJI and managed with DAIR between January 1, 2003, and December 31, 2018, at a single institution was performed. Twenty-six elbows met the inclusion criteria during the study period. All DAIR procedures included in this study represented an attempt to manage an acute PJI with surgical irrigation and débridement without removal of the elbow arthroplasty components, followed by long-term systemic antimicrobial therapy. DAIR failure was defined as recurrence of PJI, unplanned re-operation for infection, or death secondary to infection. A Cox proportional hazards model was used to identify possible risk factors for failure. RESULTS: DAIR failed in 17 cases of elbow PJI with a failure rate of 65% at 2 years (95% confidence interval: 41.3%-79.6%). The median time to failure from DAIR was 43 days (interquartile range: 27-114). We found that DAIR failed in all cases with sinus tracts or negative cultures. The group with favorable outcomes had a shorter median duration of symptoms (5 vs. 18 days, P = .65) and a higher proportion of monomicrobial infections (58.8% vs. 88.9%, P = .19) compared to those with unfavorable outcomes. However, with the numbers available, none of the possible risk factors analyzed for association with failure reached statistical significance. CONCLUSION: DAIR for elbow PJI was associated with high rates of failure. Possible risk factors for failure may include the presence of sinus tract, longer duration of symptoms, and culture-negative infection. Although the relatively low morbidity of DAIR compared with total elbow arthroplasty implant resection for a one-stage or two-stage reimplantation is attractive, patients considered for DAIR must know that the chance of success is limited to approximately 35%.

Factors Impacting the Yield of Image-Guided Biopsy in Native Vertebral Osteomyelitis: A 10-Year Retrospective Study.

Background: Image-guided biopsies in patients with suspected native vertebral osteomyelitis (NVO) are recommended to establish the microbiological diagnosis and guide antibiotic therapy. Despite recent advances, the microbiological yield of this procedure remains between 48% and 52%. A better understanding of factors associated with this low yield may lead to improved microbiological diagnosis. Methods: We retrospectively identified patients with suspected NVO undergoing image-guided biopsies from January 2011 to June 2021 at our institution. Two hundred nine patients undergoing 248 percutaneous biopsies were included. Demographic data, biopsy and microbiologic techniques, clinical characteristics, and antibiotic use were collected. Multivariable logistic regression analysis was conducted to determine factors associated with microbiological yield. Results: A total of 110 of 209 (52.6%) initial image-guided biopsies revealed positive microbiological results. This number increased to 121 of 209 (57.9%) when repeat image-guided biopsies were included. In multivariable analysis, aspiration of fluid was associated with a 3-fold increased odds of yielding a positive result (odds ratio [OR], 3.13; 95% confidence interval [CI], 1.39-7.04; P = .006), whereas prior antibiotic use was associated with a 3-fold decreased yield (OR, 0.32; 95% CI, .16-.65; P = .002). A univariate subgroup analysis revealed a significant association between the length of the antibiotic-free period and microbiological yield, with the lowest rates of pathogen detection at 0-3 days and higher rates as duration increased (P = .017). Conclusions: Prior antibiotic use in patients with suspected NVO was associated with a decrease in the microbiological yield of image-guided biopsies. An antibiotic-free period of at least 4 days is suggested to maximize yield. Successful fluid aspiration during the procedure also increases microbiological yield.

Truth in DAIR: Duration of Therapy and the Use of Quinolone/Rifampin-Based Regimens After Debridement and Implant Retention for Periprosthetic Joint Infections.

Background: The optimal duration of antibiotic therapy after debridement and implant retention (DAIR) for periprosthetic joint infections (PJIs) is debated. Furthermore, the best antibiotic regimens for staphylococcal PJI are also unclear. In this study, we evaluated the impact of antibiotic therapy duration on the risk of failure. We assessed the utility of rifampin-based regimens for staphylococcal PJI managed with DAIR. Methods: We performed a retrospective cohort study of patients 18 years and older diagnosed with hip and knee PJI who underwent DAIR between January 1, 2008 and 31 December 31, 2018 at Mayo Clinic, USA. The outcome was failure of DAIR. For statistical analysis, joint-stratified Cox regression models adjusted for age, sinus tract, symptom duration, and primary/revision arthroplasty were performed. Results: We examined 247 cases of PJI with a median follow-up of 4.4 years (interquartile range [IQR], 2.3-7) after DAIR. The estimated 5-year cumulative incidence of failure was 28.1% (n = 65). There was no association between the duration of intravenous (IV) antibiotics (median 42 days; IQR, 38-42) and treatment failure (P = .119). A shorter duration of subsequent oral antibiotic therapy was associated with a higher risk of failure (P = .005; eg, 90-day vs 1-year duration; hazard ratio [HR], 3.50; 95% confidence interval [CI], 1.48-8.25). For staphylococcal knee PJI, both the use and longer duration of a rifampin-based regimen were associated with a lower risk of failure (both P = .025). There was no significant association between fluoroquinolone (FQ) use and failure (HR, 0.62; 95% CI, .31-1.24; P = .172). Conclusions: The duration of initial IV antibiotic therapy did not correlate with treatment failure in this cohort of patients. Rifampin use is recommended for staphylococcal knee PJI. There was no apparent benefit of FQ use in staphylococcal PJI.

The New Precision Stewards?

The precision health era is likely to reduce and respond to antimicrobial resistance (AMR). Our stewardship and precision efforts share terminology, seeking to deliver the "right drug, at the right dose, at the right time." Already, rapid diagnostic testing, phylogenetic surveillance, and real-time outbreak response provide just a few examples of molecular advances we dub "precision stewardship." However, the AMR causal factors range from the molecular to that of global health policy. Mirroring the cross-sectoral nature of AMR science, the research addressing the ethical, legal and social implications (ELSI) of AMR ranges across academic scholarship. As the rise of AMR is accompanied by an escalating sense of its moral and social significance, what is needed is a parallel field of study. In this paper, we offer a gap analysis of this terrain, or an agenda for "the ELSI of precision stewardship." In the first section, we discuss the accomplishments of a multi-decade U.S. national investment in ELSI research attending to the advances in human genetics. In the next section, we provide an overview of distinct ELSI topics pertinent to AMR. The distinctiveness of an ELSI agenda for precision stewardship suggests new opportunities for collaboration to build the stewardship teams of the future.

Comparison of replicating and nonreplicating vaccines against SARS-CoV-2.

Most gene-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are nonreplicating vectors. They deliver the gene or messenger RNA to the cell to express the spike protein but do not replicate to amplify antigen production. This study tested the utility of replication in a vaccine by comparing replication-defective adenovirus (RD-Ad) and replicating single-cycle adenovirus (SC-Ad) vaccines that express the SARS-CoV-2 spike protein. SC-Ad produced 100 times more spike protein than RD-Ad and generated significantly higher antibodies against the spike protein than RD-Ad after single immunization of Ad-permissive hamsters. SC-Ad-generated antibodies climbed over 14 weeks after single immunization and persisted for more than 10 months. When the hamsters were challenged 10.5 months after single immunization, a single intranasal or intramuscular immunization with SC-Ad-Spike reduced SARS-CoV-2 viral loads and damage in the lungs and preserved body weight better than vaccination with RD-Ad-Spike. This demonstrates the utility of harnessing replication in vaccines to amplify protection against infectious diseases.

Prosthetic joint infections caused by Mycobacterium avium complex: a series of five cases.

Prosthetic joint infection (PJI) due to Mycobacterium avium complex (MAC) is a rare entity. There is limited guidance on management strategies and outcomes. In this paper, we describe the demographics, comorbidities, and clinical course of five patients at two academic institutions, constituting the largest series described to date.

Filamentous bacteriophage delays healing of Pseudomonas-infected wounds.

Chronic wounds infected by Pseudomonas aeruginosa (Pa) are characterized by disease progression and increased mortality. We reveal Pf, a bacteriophage produced by Pa that delays healing of chronically infected wounds in human subjects and animal models of disease. Interestingly, impairment of wound closure by Pf is independent of its effects on Pa pathogenesis. Rather, Pf impedes keratinocyte migration, which is essential for wound healing, through direct inhibition of CXCL1 signaling. In support of these findings, a prospective cohort study of 36 human patients with chronic Pa wound infections reveals that wounds infected with Pf-positive strains of Pa are more likely to progress in size compared with wounds infected with Pf-negative strains. Together, these data implicate Pf phage in the delayed wound healing associated with Pa infection through direct manipulation of mammalian cells. These findings suggest Pf may have potential as a biomarker and therapeutic target in chronic wounds.

Combination of phage therapy and cefiderocol to successfully treat Pseudomonas aeruginosa cranial osteomyelitis.

Background: Pseudomonas aeruginosa has the ability to exhibit resistance to a broad range of antibiotics, highlighting the importance of identifying alternative or adjunctive treatment options, such as phages. Patients and methods: We report the case of a 25-year-old male who experienced an accidental electrocution resulting in exposed calvarium in the left parieto-temporal region, complicated by a difficult-to-treat P. aeruginosa (DTR-P. aeruginosa) infection. Cefiderocol was the sole antibiotic with consistent activity against six bacterial isolates obtained from the infected region over a 38 day period. Results: WGS analysis identified a bla GES-1 gene as well as the MDR efflux pumps MexD and MexX in all six of the patient's ST235 DTR-P. aeruginosa isolates, when compared with the reference genome P. aeruginosa PA01 and a P. aeruginosa ST235 isolate from an unrelated patient. After debridement of infected scalp and bone, the patient received approximately 6 weeks of cefiderocol in conjunction with IV phage Pa14NPøPASA16. Some improvement was observed after the initiation of cefiderocol; however, sustained local site improvement and haemodynamic stability were not achieved until phage was administered. No medication-related toxicities were observed. The patient remains infection free more than 12 months after completion of therapy. Conclusions: This report adds to the growing literature that phage therapy may be a safe and effective approach to augment antibiotic therapy for patients infected with drug-resistant pathogens. Furthermore, it highlights the importance of the GES ß-lactamase family in contributing to inactivation of a broad range of ß-lactam antibiotics in P. aeruginosa, including ceftolozane/tazobactam, ceftazidime/avibactam and imipenem/relebactam.