Antimicrobial resistance has emerged as one of the most critical public health challenges of the 21st century, threatening to undermine the foundations of modern medicine. In 2019, bacterial infections accounted for 13.6% of all global deaths, with more than 7.7 million fatalities directly attributable to 33 bacterial pathogens, most prominently Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Resistance mechanisms are multifactorial, encompassing enzymatic degradation, target modification, efflux pump overexpression, reduced membrane permeability, and biofilm formation, often in combination, leading to multidrug-resistant, extensively drug-resistant, and pandrug-resistant phenotypes. Alarmingly, projections estimate that by 2050 AMR could result in over 10 million deaths annually. This comprehensive review synthesizes global epidemiological data, insights into bacterial resistance mechanisms, and emerging therapeutic solutions, including novel antibiotics such as lasso peptides and macrocyclic peptides (e.g., zosurabalpin), naturally derived compounds (e.g., corallopyronin, clovibactin, chlorotonil A), and targeted inhibitors (e.g., Debio 1453 for Neisseria gonorrhoeae). Addressing the AMR crisis requires coordinated international efforts, accelerated drug discovery, and the integration of innovative non-antibiotic approaches to preserve the efficacy of existing therapies and ensure preparedness against future bacterial threats.

Endocarditis with Abiotrophia defectiva represents 4.3% to 6% of all streptococcal endocarditis. The article presents diagnosis issues and the complexity of the treatment. We present the case of a female white patient, aged 26 years, who developed infectious endocarditis caused by A defectiva, in the last trimester of pregnancy, a biofilm-related infection associated with the presence of fixed braces. The diagnosis of infectious endocarditis was confirmed by the cardiac ultrasound examination that revealed a voluminous vegetation on the mitral valve, and acute mitral regurgitation caused by chordae tendinae rupture, and also by isolating Abiotrophia defectiva from two positive blood cultures. The decision to undergo surgical intervention was taken, and a mitral valve replacement was performed. Surgical intervention that was associated with board-spectrum antibiotic therapy. A defectiva, remains a rare cause of infective endocarditis, with a reserved prognosis that is motivated by the extensive valvular lesions and the risk of embolism. The use of antibiotics administered in association, in the management of infective endocarditis, is mandatory.

Streptococcus viridans, a heterogeneous group of alpha-hemolytic streptococci, is part of the normal flora of the mouth, usually responsible for dental caries (Streptococcus mutans, Streptococcus sanguinis), and pericoronitis, as well as for subacute infective endocarditis. They are responsible for 40-60% of the endocarditis cases occurring on the normal valves, especially in male patients and over 45 years of age. A change in the bacterial flora of the oral cavity is taking part after orthodontic fixed appliances are introduced into the oral cavity, change that is associated with an increased concentration of the acidogenic bacteria. Bacteraemia is the consequence of oral cavity infections, the association of infective endocarditis with fixed orthodontic appliance, as it has been described by us for the first time, caused by Abiotrophia defectiva. We present the case of a female Caucasian patient, aged 22 years, who developed infective endocarditis with Streptococcus viridans associated with fixed orthodontic appliance, located on the mitral valve, without previous cardiac pathology, and the therapeutic difficulties associated with allergic reactions (to vancomycin, and spironolactone). Repetitive haemocultures were positive with Streptococcus viridans, while transthoracic echography revealed a severe mitral failure through anteromedial segment of the anterior mitral valve leaf prolapse with eccentric jet to the posterior wall. During hospitalization, the decision to undergo surgical intervention was taken after obtaining negative haemocultures. The patient underwent surgically intervention, and a mitral valve plasty with insertion of neochords was performed. Intraoperative and subsequently post-discharge transesophageal echography, highlighted normofunctional mitral plasty with a remaining regurgitation grade I-II of IV, with good openness, minor tricuspid regurgitation, and mild pulmonary hypertension. Endocarditis with oral streptococci associated with fixed orthodontic appliance seems to be not so unlikely even in young or without previous cardiac pathology patients, requiring attention in identifying possible pre-existing cardiac conditions like mitral valve prolapse with clinical and echographic monitoring of such cases. Educating and motivating the patient to observe the oral hygiene represent key steps for an optimal oral health during orthodontic treatment. Mechanical tooth cleaning helps maintaining a good oral hygiene during fixed orthodontics and decreasing the oral health risks.

In the context of an increase number of primary and revision total hip and total knee arthroplasty performed yearly, an increased risk of complication is expected. Prosthetic joint infection (PJI) remains the most common and feared arthroplasty complication. Ralstonia pickettii is a Gram-negative bacterium, that has also been identified in biofilms. It remains an extremely rare cause of PJI. There is no report of an identification of R. pickettii on an extracted spacer loaded with antibiotic. We present the case of an 83-years-old Caucasian male patient, that underwent a right cemented total hip replacement surgery. The patient is diagnosed with an early PJI with no isolated microorganism. A debridement and change of mobile parts is performed. At the beginning of 2016, the patient in readmitted into the Orthopedic Department for sever, right abdominal and groin pain and elevated serum erythrocyte sedimentation rate and C-reactive protein. A joint aspiration is performed with a negative microbiological examination. A two-stage exchange with long interval management is adopted, and a preformed spacer loaded with gentamicin was implanted. In July 2016, based on the proinflammatory markers evolution, a shift a three-stage exchange strategy is decided. In September 2016, a debridement, and changing of the preformed spacer loaded with gentamicin with another was carried out. Bacteriological examination of the tissues sampled intraoperatively was positive for Pseudomonas aeruginosa. From the sonication fluid, no bacteria were isolated on culture or identified using the bbFISH assay. During the hospitalization period, the patient received i.v. ceftazidime 3x2g/day and p.o. ciprofloxacin 2x750mg/day, antibiotic therapy that was continued after discharge with p.o. ciprofloxacin 2x750mg/day for 6 weeks. In February 2017, a reimplantation of a revision prosthesis is performed. The retrieved spacer is sonicated, and after 4 days of incubation of the sonication fluid, R. pickettii is isolated. A long term antibiotic therapy with cotrimoxazole being prescribed. Bacteria culture of sonication fluid remains the gold standard in diagnosing prosthetic joint infections. R. pickettii remains an extremely rare cause of prosthetic joint infection. Optimal management of R. pickettii prosthetic joint infections of has not been established.

Background: PJIs following total hip and knee arthroplasty represent severe complications with broad implications, and with significant disability, morbidity, and mortality. To be able to provide correct and effective management of these cases, an accurate diagnosis is needed. Classically, acute PJIs are characterized by a preponderance of virulent microorganisms, and chronic PJIs are characterized by a preponderance of less-virulent pathogens like coagulase-negative staphylococci or Cutibacterium species. This paper aims to analyze if there are any changes in the causative microorganisms isolated in the last years, as well as to provide a subanalysis of the types of PJIs. Methods: In this single-center study, we prospectively included all retrospectively consecutive collected data from patients aged over 18 years that were hospitalized from 2016 through 2022, and patients that underwent a joint arthroplasty revision surgery. A standardized diagnostic protocol was used in all cases, and the 2021 EBJIS definition criteria for PJIs was used. Results: 114 patients were included in our analysis; of them, 67 were diagnosed with PJIs, 12 were acute/acute hematogenous, and 55 were chronic PJIs. 49 strains of gram-positive aerobic or microaerophilic cocci and 35 gram-negative aerobic bacilli were isolated. Overall, Staphylococcus aureus was the most common isolated pathogen, followed by coagulase-negative staphylococci (CoNS). All cases of acute/acute hematogenous PJIs were caused by gram-positive aerobic or microaerophilic cocci pathogens. Both Staphylococcus epidermidis and methicillin-resistant S. aureus were involved in 91.66% of the acute/acute hematogenous PJIs cases. 21.8% of the chronic PJIs cases were caused by pathogens belonging to the Enterobacterales group of bacteria, followed by the gram-negative nonfermenting bacilli group of bacteria, which were involved in 18.4% of the cases. 12 chronic cases were polymicrobial. Conclusion: Based on our findings, empiric broad-spectrum antibiotic therapy in acute PJIs could be focused on the bacteria belonging to the gram-positive aerobic or microaerophilic cocci, but the results should be analyzed carefully, and the local resistance of the pathogens should be taken into consideration.

Background: There is no clear distinction in the literature regarding the positivity trends of bacterial cultures in acute and chronic prosthetic joint infections. Methods: We prospectively included in this study all consecutive patients, aged over 18 years, that were hospitalized from September 2016 through December 2019, that underwent a joint arthroplasty revision surgery. Results: Forty patients were included in our analysis, 11 acute/acute hematogenous and 29 chronic PJIs. We were able to identify all strains of acute/acute hematogenous PJIs within 3 days, whereas this took 8 days for chronic PJIs. Sonication fluid cultures increased the positivity rate and helped in identifying rare pathogens such as Ralstonia pickettii from chronic PJIs, but also increased the number of identified strains from acute PJIs. Culturing synovial fluid in our study did not seem to have a clear benefit compared to sonication fluid and periprosthetic tissue cultures. Conclusion: There was a different positivity trend in bacterial cultures. Empiric broad-spectrum antibiotic therapy can be re-evaluated after 3 days for acute PJIs. A prolonged incubation time, especially in the case of chronic PJIs, is mandatory; however, extending the incubation period beyond 14 days would not further improve the ability to identify microorganisms.