Adjunctive Antibiotics Research Articles

Does adjunctive phototherapy have better outcomes than adjunctive antibiotic therapy for the management of peri-implantitis?

Does adjunctive phototherapy have better outcomes than adjunctive antibiotic therapy for the management of peri-implantitis?

The role of the oral microbiota in the causal effect of adjunctive antibiotics on clinical outcomes in stage III–IV periodontitis patients

BackgroundPeriodontitis, a prevalent chronic inflammatory disease, offers insights into the broader landscape of chronic inflammatory conditions. The progression and treatment outcomes of periodontitis are closely related to the oral microbiota’s composition. Adjunctive systemic Amoxicillin 500 mg and Metronidazole 400 mg, often prescribed thrice daily for 7 days to enhance periodontal therapy’s efficacy, have lasting effects on the oral microbiome. However, the precise mechanism through which the oral microbiome influences clinical outcomes in periodontitis patients remains debated. This investigation explores the pivotal role of the oral microbiome's composition in mediating the outcomes of adjunctive systemic antibiotic treatment.MethodsSubgingival plaque samples from 10 periodontally healthy and 163 periodontitis patients from a randomized clinical trial on periodontal therapy were analyzed. Patients received either adjunctive amoxicillin/metronidazole or a placebo after mechanical periodontal treatment. Microbial samples were collected at various intervals up to 26 months post-therapy. Using topic models, we identified microbial communities associated with normobiotic and dysbiotic states, validated with 86 external and 40 internal samples. Logistic regression models evaluated the association between these microbial communities and clinical periodontitis parameters. A Directed Acyclic Graph (DAG) determined the mediating role of oral microbiota in the causal path of antibiotic treatment effects on clinical outcomes.ResultsWe identified clear distinctions between dysbiotic and normobiotic microbial communities, differentiating healthy from periodontitis subjects. Dysbiotic states consistently associated with below median %Pocket Probing Depth ≥ 5 mm (OR = 1.26, 95% CI [1.14–1.42]) and %Bleeding on Probing (OR = 1.09, 95% CI [1.00–1.18]). Factors like microbial response to treatment, smoking, and age were predictors of clinical attachment loss progression, whereas sex and antibiotic treatment were not. Further, we showed that the oral microbial treatment response plays a crucial role in the causal effect of antibiotic treatment on clinical treatment outcomes.ConclusionsThe shift towards a normobiotic subgingival microbiome, primarily induced by adjunctive antibiotics, underscores the potential for microbiome-targeted interventions to enhance therapeutic efficacy in chronic inflammatory conditions. This study reaffirms the importance of understanding the oral microbiome's role in periodontal health and paves the way for future research exploring personalized treatment strategies based on individual microbiome profiles.D_npUcg1WaKKucWMF28BqgVideo

The association between periodontal microbial biomarkers and primary therapy outcome

ObjectiveThis study aims to analyse the association between the baseline microbial load of selected periodontopathogenic bacteria collected from gingival crevicular fluid (GCF) and the primary outcome of steps I and II therapy.Materials and methods222 patients with stage III periodontitis were included into this retrospective analysis that received steps 1 and 2 periodontal therapy without adjunctive systemic antibiotics. Baseline GCF samples were quantitatively analysed using ELISA-based kits for levels of periodontopathogens (Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans (Aa), Prevotella intermedia (Pi), Fusobacterium nucleatum (Fn), Treponema denticola (Td), and Tannerella forsythia (Tf)) and associated with the primary therapy outcome using a “treat-to-target” therapy endpoint (TE) defined as ≤ 4 sites with PD ≥ 5 mm six months after therapy.Results38.2% of the patients achieved TE. Patients failing to achieve TE revealed significantly increased levels of Pg, Fn, and Tf at baseline (Pg: p = 0.010, Fn: p = 0.008 Tf: p = 0.004). Multivariate binary logistic regression adjusted for sex, mean probing depth, diabetes, and current smoking status showed an independent relationship between Tf and the TE (aOR 2.570, p = 0.023).ConclusionIncreased microbial load is associated with decreased responsiveness to therapy. The findings suggest that specifically baseline Tf levels are associated with poorer treatment outcomes and might improve the accuracy of periodontal diagnosis.Clinical relevanceThe findings of this study support the concept of a critical biomass that is sufficient to induce and maintain an immune response within the periodontal pocket, which ultimately leads to irreversible tissue destruction. However, calculating this level in advance may serve as an early indicator for intervention.Key findingBaseline Tannerella forsythia levels are associated with poorer treatment outcome.

HOCl-producing electrochemical bandage is active in murine polymicrobial wound infection.

New approaches are needed to combat the rise of antimicrobial-resistant infections. The HOCl-producing electrochemical bandage (e-bandage) leverages in situ generation of HOCl, a natural biocide, for broad-spectrum killing of wound pathogens. Unlike traditional therapies that may exhibit limited activity against biofilms and antimicrobial-resistant organisms, the e-bandage offers a potent, standalone solution that does not contribute to further resistance or require adjunctive antibiotic therapy. Here, we show the ability of the e-bandage to address polymicrobial infection by antimicrobial resistant clinical isolates of Staphylococcus aureus and Pseudomonas aeruginosa, two commonly isolated, co-infecting wound pathogens. Effectiveness of the HOCl-producing e-bandage in reducing pathogen load while minimizing tissue toxicity and avoiding the need for systemic antibiotics underscores its potential as a tool in managing complex wound infections.

Do systemic amoxicillin and metronidazole during the non-surgical peri-implantitis treatment phase prevent the need for future surgical treatment? A retrospective long-term cohort study.

The aim of this retrospective long-term follow-up of a 3-month RCT was to assess whether non-surgical peri-implantitis treatment with adjunctive systemic antibiotics influenced the need for additional surgical treatment. Patients enrolled in an aftercare programme following non-surgical peri-implantitis treatment, with or without systemic amoxicillin and metronidazole, were analysed. Data had previously been collected pre-treatment (T0) and 3 months after treatment (T1) and were additionally collected during subsequent aftercare visits, until the final assessment (T2). Primary outcome was the need for additional surgical peri-implantitis therapy during the aftercare programme, analysed via Kaplan-Meier analysis and Cox regression. Secondary outcomes involved clinical parameters, assessed using parametric and non-parametric tests. Forty-five patients (22 AB- group, 23 AB+ group) were included. The mean follow-up time between T1 and T2 was 35.9 months (SD = 21.0). 73.9% of the AB+ group and 50.0% of the AB- group did not receive additional surgical therapy (log-rank test, p = .110). The adjusted Cox regression model did not provide a significant result for antibiotics (β = .441, 95% CI = 0.159-1.220, p = .115). Univariable regression analysis highlighted the influence of baseline peri-implant pocket depth on the need for surgical treatment (β = 1.446, 95% CI = 1.035-2.020, p = .031). Systemic amoxicillin and metronidazole administered during non-surgical peri-implantitis treatment do not seem to prevent the need for additional surgical therapy in the long term, during a structured aftercare programme.

Does Adjunctive Clindamycin Have a Role in Staphylococcus aureus Bacteremia? A Protocol for the Adjunctive Treatment Domain of the Staphylococcus aureus Network Adaptive Platform (SNAP) Randomized Controlled Trial.

The use of adjunctive antibiotics directed against exotoxin production in Staphylococcus aureus bacteremia (SAB) is widespread, and it is recommended in many guidelines, but this is based on limited evidence. Existing guidelines are based on the theoretical premise of toxin suppression, as many strains of S. aureus produce toxins such as leukocidins (eg, Panton-Valentine leukocidin, toxic shock syndrome toxin 1, exfoliative toxins, and various enterotoxins). Many clinicians therefore believe that limiting exotoxin production release by S. aureus could reduce its virulence and improve clinical outcomes. Clindamycin, a protein synthesis inhibitor antibiotic, is commonly used for this purpose. We report the domain-specific protocol, embedded in a large adaptive, platform trial, seeking to definitively answer this question. The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is a pragmatic, randomized, multicenter adaptive platform trial that aims to compare different SAB therapies, simultaneously, for 90-day mortality rates. The adjunctive treatment domain aims to test the effectiveness of adjunctive antibiotics, initially comparing clindamycin to no adjunctive antibiotic, but future adaptations may include other agents. Individuals will be randomized to receive either 5 days of adjunctive clindamycin (or lincomycin) or no adjunctive antibiotic therapy alongside standard-of-care antibiotics. Most participants with SAB (within 72 hours of index blood culture and with no contraindications) will be eligible to participate in this domain. Prespecified analyses are defined in the statistical appendix to the core protocol, and domain-specific secondary analyses will be adjusted for resistance to clindamycin, disease phenotype (complicated or uncomplicated SAB) and Panton-Valentine leukocidin-positive isolate.

Comparative Study of Systemic vs. Local Antibiotics with Subgingival Instrumentation in Stage III-IV Periodontitis: A Retrospective Analysis.

To improve the clinical and microbiological outcomes of non-surgical mechanical periodontal therapy, the adjunctive use of antimicrobials has been utilized in treating moderate-to-severe periodontitis. In our study, the retrospective design included previously collected health-related patient data, obtained from the printed and digital charts of patients who received systemic or local antibiotic adjuncts to SI (subgingival instrumentation). A total of 34 patients (diagnosed with generalized Stage III/IV periodontitis) met the inclusion and exclusion criteria and were evaluated. The samples were tested for the following bacterial strains: Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Porphyromonas gingivalis (P. gingivalis), Prevotella intermedia (P. intermedia), Tanererella forsythia (T. forsythia), and Treponema denticola (T. denticola). The inter-group comparisons of the bacterial species did not show statistically significant differences between groups. The present study aimed to evaluate the clinical effects after SI and the adjunctive use of systemically administered (SA) AMX (amoxicillin) + MET (metronidazole) (administered for 7 days), with locally delivered (LDD) piperacillin + tazobactam in step 2 of periodontal therapy. Results: Overall, all parameters were improved in the groups, with a significant difference in inter-group comparison regarding the full-mouth bleeding score (FMBS) (p < 0.05) in favor of the SA group, and the p-value < 0.05 was considered to be statistically significant. Statistically significant PPD (probing pocket depth) reductions and CAL (clinical attachment level) gains were observed in both groups at the 3-month follow-up. In conclusion, within the limitations, the outcomes of this study suggest that SI, with adjunctive local or systemic antibiotic therapy, provided comparable clinical improvements. Systemic AMX + MET protocols were more efficacious with regard to the reduction in FMBS. Follow-up studies with larger patient numbers are needed to further investigate this effect.

Systemic antibiotics in the surgical treatment of peri-implantitis: A randomized placebo-controlled trial.

To study the clinical, radiographic and microbiological outcomes after surgical treatment of peri-implantitis, with or without adjunctive systemic antibiotics. Eighty-four patients (113 implants) with peri-implantitis were randomized into three groups (A, amoxicillin and metronidazole; B, phenoxymethylpenicillin and metronidazole; or C, placebo). Treatment included resective surgery and implant surface decontamination with adjunctive antibiotics or placebo. Primary outcomes were probing pocket depth (PPD) reduction and marginal bone level (MBL) stability. Secondary outcomes were treatment success (defined as PPD ≤ 5 mm, bleeding on probing [BOP] ≤ 1site, absence of suppuration on probing [SOP] and absence of progressive bone loss of >0.5 mm), changes in BOP/SOP, mucosal recession (REC), clinical attachment level (CAL), bacterial levels and adverse events. Outcomes were evaluated for up to 12 months. The impact of potential prognostic indicators on treatment success was evaluated using multilevel logistic regression analysis. A total of 76 patients (104 implants) completed the study. All groups showed clinical and radiological improvements over time. Statistically significant differences were observed between groups for MBL stability (A = 97%, B = 89%, C = 76%), treatment success (A = 68%, B = 66%, C = 28%) and bacterial levels of Aggregatibacter actinomycetemcomitans and Tannerella forsythia, favouring antibiotics compared to placebo. Multiple regression identified antibiotic use as potential prognostic indicator for treatment success. Gastrointestinal disorders were the most reported adverse events in the antibiotic groups. Adjunctive systemic antibiotics resulted in additional improvements in MBL stability. However, the potential clinical benefits of antibiotics need to be carefully balanced against the risk of adverse events and possible antibiotic resistance.

Treatment of peri-implantitis with a flapless surgical access combined with implant surface decontamination and adjunctive systemic antibiotics: A retrospective case series study.

To evaluate the effectiveness of a flapless surgical approach in the treatment of peri-implantitis and to explore the factors influencing its outcome. The present retrospective study evaluated patients with at least one implant diagnosed with peri-implantitis and treated with a flapless surgical access, with or without systemic antimicrobials, curettage and, when needed, prostheses modification. Clinical and radiographic parameters were assessed at baseline and at 3 months and at least 12 months. The primary outcome was disease resolution (≤1 bleeding sites, probing depth [PD] ≤5 mm, no bone loss >0.5 mm). Multilevel regression analyses were used to identify predictors influencing the probability of attaining disease resolution. One hundred and seventeen patients with 338 implants were included. Disease resolution was attained in 54.4% of the 338 implants receiving flapless surgical access. At the end of the follow-up period, 111 patients (94.9%) with 295 implants (87.3%) did not require any further treatment, with 81.4% of these implants presenting PD ≤ 5 mm. History of periodontitis and PD at baseline were identified as negative predictors, while compliance with supportive peri-implant care, a machined surface and the adjunctive use of systemic azithromycin or metronidazole were identified as positive predictive factors for disease resolution. A flapless surgical approach led to disease resolution in 54.4% of the implants with peri-implantitis. Several risk/protective predictors for disease resolution were identified.

Clinical and Radiographic Outcomes of Adjunctive Phototherapy Versus Antibiotic Therapy Against Peri-Implant Diseases: A Systematic Review and Meta-Analysis.

Background: Peri-implantitis, an inflammatory condition in implant tissues, requires bacterial eradication and implant surface decontamination, with aPDT as a helpful surgical adjunct. Objective:This project was designed to investigate the effect of antibiotic therapy versus aPDT, as adjuncts to conventional mechanical debridement (MD), on the peri-implant clinical and/or radiographic parameters among patients with peri-implant diseases. Methods: A comprehensive search was conducted across electronic databases, including PubMed, Scopus, and Web of Science, up to and including April 2023, without any restriction on the language and year of publication, focusing the following research question: "Does adjunctive aPDT improve the peri-implant clinical and/or radiographic parameters in treating peri-implant diseases compared to antibiotic therapy?" Statistical analysis was performed on peri-implant clinical [plaque index (PI), probing depth (PD), and bleeding on probing (BOP)] and radiographic parameters [marginal bone loss (MBL)]. The study included six randomized controlled trials and one clinical (nonrandomized) study. Results: The systematic review findings indicate that the application of aPDT as an adjunct to MD is equally effective as adjunctive antibiotic therapy in improving peri-implant clinical parameters and radiographic parameters in patients with peri-implant diseases. Only two studies were classified as having a low risk of bias (RoB), two were assessed as having an unclear RoB, and the remaining three studies were determined to have a high RoB. However, the meta-analysis results revealed no statistically significant difference in peri-implant PI, PD, and MBL scores between patients treated with adjunct aPDT or adjunct antibiotic therapy. Notably, there was a statistically significant difference favoring adjunct aPDT in peri-implant BOP values compared to the control group. Conclusions: Despite the limited number of included studies and the significant heterogeneity among them, the findings suggest that aPDT yields comparable peri-implant clinical and radiographic outcomes to adjunctive antibiotic therapy, as adjuncts to MD, for the potential treatment of peri-implant diseases.

ADJUNCTIVE ANTIBIOTICS MAY REDUCE PROBING DEPTH, INCREASE BONE LEVEL GAIN, AND CONTRIBUTE TO OVERALL SUCCESS IN PERI-IMPLANTITIS TREATMENT FOR UP TO 12 MONTHS POSTOPERATIVELY

Wang Y, Chen CY, Stathopoulou PG, Graham LK, Korostoff J, Chen YW. Efficacy of Antibiotics Used as an Adjunct in the Treatment of Peri-implant Mucositis and Peri-implantitis: A Systematic Review and Meta-analysis. Int J Oral Maxillofac Implants. 2022 Mar-Apr;37(2):235-249. doi:10.11607/jomi.9220. PMID: 35476853. None. Systematic review with meta-analysis of data.

Evaluating the Long-Term Outcomes of Periodontal Surgery vs. Non-Surgical Treatment in Aggressive Periodontitis.

Aggressive periodontitis is a severe form of periodontal disease characterized by rapid tissue destruction and tooth loss. The optimal treatment approach for managing this condition remains a topic of debate. A retrospective cohort study was conducted, involving patients diagnosed with aggressive periodontitis who received either surgical or non-surgical treatment between 2010 and 2020. Clinical and radiographic data were collected at baseline and regular intervals over a 5-year follow-up period. Surgical interventions included flap surgery, guided tissue regeneration, and bone grafting, while non-surgical treatments comprised scaling and root planning with or without adjunctive antibiotics. The primary outcomes assessed included changes in probing depth, clinical attachment level, tooth loss, and patient-reported quality of life measures. A total of 120 patients were included in the study, with 60 patients in each treatment group. The surgical group demonstrated significantly greater reductions in probing depth and gains in clinical attachment level compared to the non-surgical group (P < 0.05). Tooth loss was significantly lower in the surgical group over the 5 years (P < 0.01). Patient-reported outcomes also favored the surgical group, with improved oral health-related quality of life. However, the surgical group had a higher incidence of postoperative complications. This study suggests that periodontal surgery yields superior long-term outcomes in the management of aggressive periodontitis compared to non-surgical treatment.

Potentiation and Mechanism of Berberine as an Antibiotic Adjuvant Against Multidrug-Resistant Bacteria.

The growing global apprehension towards multi-drug resistant (MDR) bacteria necessitates the development of innovative strategies to combat these infections. Berberine (BER), an isoquinoline quaternary alkaloid derived from various medicinal plants, has surfaced as a promising antibiotic adjuvant due to its ability to enhance the effectiveness of conventional antibiotics against drug-resistant bacterial strains. Here, we overview the augmenting properties and mechanisms of BER as an adjunctive antibiotic against MDR bacteria. BER has been observed to exhibit synergistic effects when co-administered with a range of antibiotics, including β-lactams, quinolones, aminoglycosides, tetracyclines, macrolides, lincosamides and fusidic acid. The adjunctive properties of BER led to an increase in antimicrobial effectiveness for these antibiotics against the corresponding bacteria, a decrease in minimal inhibitory concentrations, and even the reversal from resistance to susceptibility sometimes. The potential mechanisms responsible for these effects included the inhibition of antibiotic efflux, the disruption of biofilm formation, the modulation of host immune responses, and the restoration of gut microbiota homeostasis. In brief, BER demonstrated significant potential as an antibiotic adjuvant against MDR bacteria and is a promising candidate for combination therapy. Further research is necessary to fully elucidate its mechanism of action and address the challenges associated with its clinical application.

Recent developments in the diagnosis, treatment, and management of Papillon-Lefèvre Syndrome.

A systematic search of PubMed, LIVIVO, and Ovid was conducted up to March 2021. These databases were searched for relevant clinical studies on periodontal treatment success in individuals with Papillon-Lefèvre syndrome (PLS). Clinical studies reporting successful treatment outcomes defined as the loss of four or fewer permanent teeth due to periodontitis and the arrest of periodontitis or probing depths of 5 mm or less in individuals with PLS followed up for ≥24 months were included, and data extracted. Twelve studies reporting on nine PLS patients met the inclusion criteria. The extracted main outcomes in the studies reporting successful periodontal treatment in PLS were as follows: (1) clinical and genetic diagnosis of PLS; (2) age at baseline; (3) initial dental, periodontal parameters, and microbiological assessment, if available; (4) description of disease progression and applied therapies; and (5) outcome and follow-up. Twelve studies reporting nine individuals were included. The timely extraction of affected or all primary teeth, compliance with oral hygiene instructions, supra- and subgingival debridement within frequent supportive periodontal care intervals, and adjunctive systemic antibiotic therapy in most patients affected a halt in disease progression. Suppression of Aggregatibacter actinomycetemcomitans below detection limits was associated with periodontal stabilization. An intensive, multidisciplinary approach with strict compliance may enable the decelerated progression of PLS-associated periodontitis. The early diagnosis of PLS and the suppression of A. actinomycetemcomitans below the detection level might be critical factors for treatment success. It required significant effort and patient compliance. The study emphasized the importance of timely interventions, oral hygiene maintenance, regular professional dental care, and, in some cases, systemic antibiotics.

P25 Ceftazidime/avibactam and cefiderocol use in adults in a South London Trust

Abstract Background NHS England now subsidizes pharmaceutical firms to invest in new antibiotic development. Currently, this applies to cefiderocol and ceftazidime/avibactam for treatment of patients with severe bacterial infections non-responsive to other antibiotics. The aims are to reduce the risk of resistance and protect the longevity of antimicrobials by restricting use to certain patients with sepsis, hospital/ventilator-associated pneumonia and bloodstream infections. Acute hospital trusts bear most of the drug cost but receive a 19%–33% discount. Methods Pharmacy records for ceftazidime/avibactam or cefiderocol from July to December 2022 were accessed. Medical notes and laboratory systems were interrogated for clinical information as part of required Blueteq reporting. Results 15 prescriptions of cefiderocol and ceftazidime/avibactam were reviewed in 14 patients. The total number of days of therapy was 268 (112 + 156 for cefiderocol and ceftazidime/avibactam respectively). Median treatment duration was 11.5 (IQR 7–16.5) and 10 (IQR 5–22) days for cefiderocol and ceftazidime/avibactam, respectively. All infections were considered healthcare associated. Target organisms were Enterobacterales (39%), Pseudomonas spp. (28%), Acinetobacter spp. (11%) and Stenotrophomonas spp. (22%) (Figure 2). Twenty-one percent had polymicrobial infections and 50% of patients received adjunctive antibiotics (25% cefiderocol and 71% ceftazidime/avibactam). In-hospital mortality was 64%. All Enterobacterales, Acinetobacter and Pseudomonas isolates underwent phenotypic carbapenem susceptibility testing, and 100% of these were found to be resistant to at least one carbapenem. Where phenotypic carbapenem resistance was detected in Enterobacterales, reflex carbapenemase testing in accordance with laboratory protocol was performed for 71%, with a gene detected in 71% of these. For carbapenem-resistant Acinetobacter isolates, reflex ceftazidime/avibactam testing in accordance with laboratory protocol was performed in 100%. There is no local protocol in place for reflex cefiderocol/ceftazidime/avibactam susceptibility testing in multidrug-resistant Pseudomonas isolates. The median turnaround time from sample collection to result authorization was 2 (IQR 1.75–10) and 7 (IQR 2–9) days for cefiderocol and ceftazidime/avibactam, respectively. Use was empirical at the time of prescription in 40% of cases and appropriate (based on final AST results) in 80%. An infection specialist was involved in the initial prescription in all cases, and bedside review occurred in all cases. Conclusions Use of high-cost antimicrobials is currently led by infection specialists in our Trust, often empirical initially but usually appropriate based on final results. Practices around reflex expanded susceptibility of clinically significant MDR Gram negatives, and carbapenemase testing of Enterobacterales should be improved. Optimizing these processes should be prioritized as the infection sciences laboratory moves to a central hub.

Biocompatibility and Safety Assessment of Combined Topical Ozone and Antibiotics for Treatment of Infected Wounds.

Wound infections with antibiotic-resistant bacteria, particularly the Gram-negative strains, pose a substantial health risk for patients with limited treatment options. Recently topical administration of gaseous ozone and its combination with antibiotics through portable systems has been demonstrated to be a promising approach to eradicate commonly found Gram-negative strains of bacteria in wound infections. However, despite the significant impact of ozone in treating the growing number of antibiotic-resistant infections, uncontrolled and high concentrations of ozone can cause damage to the surrounding tissue. Hence, before such treatments could advance into clinical usage, it is paramount to identify appropriate levels of topical ozone that are effective in treating bacterial infections and safe for use in topical administration. To address this concern, we have conducted a series of in vivo studies to evaluate the efficacy and safety of a portable and wearable adjunct ozone and antibiotic wound therapy system. The concurrent ozone and antibiotics are applied through a wound interfaced gas permeable dressing coated with water-soluble nanofibers containing vancomycin and linezolid (traditionally used to treat Gram-positive infections) and connected to a portable ozone delivery system. The bactericidal properties of the combination therapy were evaluated on an ex vivo wound model infected with Pseudomonas aeruginosa, a common Gram-negative strain of bacteria found in many skin infections with high resistance to a wide range of currently available antibiotics. The results indicated that the optimized combination delivery of ozone (4 mg h-1) and topical antibiotic (200 μg cm-2) provided complete bacteria eradication after 6 h of treatment while having minimum cytotoxicity to human fibroblast cells. Furthermore, in vivo local and systemic toxicity studies (e.g., skin monitoring, skin histopathology, and blood analysis) on pig models showed no signs of adverse effects of ozone and antibiotic combination therapy even after 5 days of continuous administration. The confirmed efficacy and biosafety profile of the adjunct ozone and antibiotic therapy places it as a strong candidate for treating wound infection with antimicrobial-resistant bacteria and further pursuing human clinical trials.

Antibiotics in the non-surgical treatment of peri-implantitis.

Four electronic databases (MEDLINE via Pubmed; EMBASE via Ovid; EBSCO Dentistry and Oral Science Source), in addition to six related journals (Clinical Implant Dentistry and Related Research; Clinical Oral Implants Research; International Journal of Oral and Maxillofacial Implants; International Journal of Oral Implantology; Journal of Clinical Periodontology; Journal of Periodontology), were searched for publications until 2022. Randomised controlled trials (RCTs), evaluating the effectiveness of local or systemic antibiotics as an adjunct in the non-surgical treatment (NST) for peri-implantitis (PI), were assessed. The eligibility criteria included RCTs with a parallel group, split-mouth design and appropriate NST interventions over a three to twelve month period. Data were extracted from RCTs to capture a multitude of primary outcomes, including: implant success rate, radiographic marginal bone loss rate, periodontal health changes and PI resolution. Risk of bias assessments were made using the Cochrane Collaboration's tool, by two authors independently and in duplicate. RCTs with similar observation periods and interventions were included in the meta-analyses. Random-effects meta-analyses of mean differences or relative risks with 95% confidence intervals were calculated, in additional to data heterogeneity calibration through I2 statistics. Following the screening of 270 papers, six RCTs were included, which resulted in the evaluation of 391 patients (375 implants). Adjunctive local antibiotic therapy at disease sites showed statistically significant periodontal outcomes; improvements in success rate (risk ratio = 9.89; 95% CI 2.39-40.84), probing pocket depth (mean difference (MD) = 0.6 mm; 95% CI 0.42-0.78) and bleeding on probing (MD = 0.15%; 95% CI 0.10-0.19). Conversely, adjunctive systemic antibiotics improved probing pocket depths (MD = 1.15 mm; 95% CI 0.31-1.99) and probing attachment levels only (MD = 1.10 mm; 95% CI 0.13-2.08). Across the six included RCTs, the bone loss rate and PI resolution rate determined no significant differences between the groups; mirrored in the single studies and in the meta-analysis. Disease resolution ranged from 2 to 65%. Two of the studies were found to be at low risk of bias and four presented with some concerns. Adjunctive antibiotics aid NST. However, the heterogeneity of study methods and low quality of current RCTs evidenced, deem their role in NSTs of PI as inconclusive.

A Local Desiccant Antimicrobial Agent as an Alternative to Adjunctive Antibiotics in the Treatment of Periodontitis: A Narrative Review.

Periodontitis is one of the most common oral polymicrobial infectious diseases induced by the complex interplay between the altered subgingival microbiota and the host's dysregulated immune-inflammatory response, leading to the initiation of progressive and irreversible destruction of the periodontal tissues and eventually to tooth loss. The main goal of cause-related periodontal therapy is to eliminate the dysbiotic subgingival biofilm in order to arrest local inflammation and further periodontal tissue breakdown. Because, in some cases, subgingival mechanical instrumentation has limited efficiency in achieving those goals, various adjunctive therapies, mainly systemic and locally delivered antimicrobials, have been proposed to augment its effectiveness. However, most adjunctive antimicrobials carry side effects; therefore, their administration should be precociously considered. HybenX® (HY) is a commercial therapeutical agent with decontamination properties, which has been studied for its effects in treating various oral pathological conditions, including periodontitis. This review covers the current evidence regarding the treatment outcomes and limitations of conventional periodontal therapies and provides information based on the available experimental and clinical studies related to the HY mechanism of action and effects following its use associated with subgingival instrumentation and other types of dental treatments.

980. Enterobacter: An Early-Onset Pathogen of Prosthetic Hip and Knee Infections with Poor Prognoses

Abstract Background Enterobacter sp. is a gram-negative, often drug-resistant bacillus that is classically identified from mucosal surfaces, such as pulmonary or urinary tracts. Despite its virulence, Enterobacter represents a less common pathogen in prosthetic joint infections (PJI). This study aims to resolve the current paucity of described clinical characteristics and treatment success of Enterobacter PJI. Methods Thirty-three patients with Enterobacter aerogenes-, cloaecae/asburiae-, or hormachei-positive PJIs were identified at a single institution. Infection clearance was defined as absence of infection or repeat surgery at one year and off all adjunct antibiotic therapy. Patient demographics, PJI characteristics, treatments, and clinical outcomes were compared between patients with and without clearance. Results In this cohort, mean age was 66.8 years (SD: 11.6), mean BMI was 31.0 (SD: 7.1), and mean Elixhauser Comorbidity Score was 9.1 (SD: 4.5). 54.5% had a prior PJI in the same joint, and 87.9% had more than one prior surgery in that joint. Median time of PJI diagnosis after surgery was 22 days [IQR: 18-60]. Patients initially treated with debridement antibiotics and implant retention (n=11) had a 45.5% clearance rate, compared to 23.1% for 2-stage exchange (n=13) and 44.4% for those requiring resection arthroplasty or amputation (n=9). With a median follow-up of 2.9 years, final joint outcomes included resection arthroplasty in 9 (27.3%), above-knee amputation in 7 (21.2%), definitive treatment with an articulating spacer in 6 (18.2%), and arthrodesis in 2 (6.1%) patients. Conclusion Enterobacter PJI often presents acutely and is a difficult pathogen to treat. The outcomes of our cohort reflect the virulence of Enterobacter, with high rates of failure and ultimate joint- or limb-sacrificing procedure. Despite being a less common cause of PJI, prognosis is exceptionally poor with traditional treatment algorithms when compared to historical cohorts of more common pathogens. Disclosures William A. Jiranek, MD, Biomech Holdings LLC: Stocks/Bonds|DePuy, A Johnson &amp; Johnson Company: IP royalties Thorsten M. Seyler, MD, PhD, Heraeus: Paid consultant|Pattern Health: IP royalties|Restor3d: IP royalties|Smith &amp; Nephew: Paid consultant|Total Joint Orthopedics: Paid consultant|Zimmer: research.

Antibiotics as Adjunctive Therapy in the Non-Surgical Treatment of Peri-Implantitis: A Systematic Review and Meta-Analysis.

The role of antibiotics as adjunctive therapy in the non-surgical treatment of peri-implantitis is uncertain. The aim of this systematic review of randomized controlled trials was to assess the efficacy of antibiotic therapy, local or systemic, as an adjunctive to the non-surgical therapy of peri-implantitis. Primary outcomes were: implant success rate and complications, changes in radiographic bone level, probing pocket depth (PPD), probing attachment level (PAL), bleeding on probing (BOP) and peri-implantitis resolution. Six studies were included: two using topical and four systemic antibiotics. Adjunctive local antibiotics improved PPD (mean difference (MD) = 0.6 mm; 95% CI 0.42-0.78), BOP (MD = 0.15% (95% CI 0.10, 0.19)) and the success rate (risk ratio = 9.89; 95% CI 2.39-40.84). No significant difference in bone level and success rate were found with the use of systemic antibiotics, although they appeared to improve PPD (MD = 1.15 mm; 95% CI 0.31-1.99) and PAL (MD = 1.10 mm; 95% CI 0.13-2.08). Within the limitations of this review, the adjunctive local antibiotics showed improved outcomes in terms of success rate, PPD and BOP, while adjunctive systemic antibiotics improved PPD and PAL only. Peri-implantitis resolution was about 20-30% using adjunctive local antibiotics, whilst it ranged from 2% to 65% with adjunctive systemic antibiotics. Findings are still controversial, since they are based on few studies with high heterogeneity, at the uncertain or high risk of bias and involve few patients. Non-surgical debridement and maintenance periodontal support therapy remain pivotal and the adjunctive use of antibiotics for peri-implantitis cannot be routinely recommended, even considering the increasing concern on antibiotic resistance.