Prolonged Antibiotic Treatment Research Articles

Antimicrobial susceptibility testing of bone and joint pathogens using isothermal microcalorimetry

The rise in osteomyelitis and periprosthetic joint infections, in combination with increasing life expectancy and the prevalence of diabetes, underscores the urgent need for rapid and accurate diagnostic tools. Conventional culture‐based methods are often time‐consuming and prone to false‐negatives, leading to prolonged and inappropriate antibiotic treatments. This study aims to improve osteomyelitis diagnostics by decreasing the time to detection and the time to an antibiotic susceptibility result to enable a targeted treatment using isothermal microcalorimetry (IMC). IMC measures heat flow in real‐time, providing insights into bacterial metabolism without the need for labeling. Using clinical isolates from bone infections, assessing their response to antibiotics through IMC, we demonstrated that IMC could detect bacteria within 4 h and determine antimicrobial susceptibility profiles within 2–22 h (median 4.85, range 1.28–21.78). This is significantly faster than traditional methods. A decision tree, based on antibiotic susceptibility, accurately categorized pathogens, achieving high accuracy (74–100%), sensitivity (100%), and specificity (65–100%). These findings suggest that IMC could redefine diagnostics of bone and joint infections and potentially infections in general, offering timely and precise treatment guidance, thereby improving patient outcomes and reducing health care burdens. Further optimization and clinical validation are needed to fully integrate IMC into routine diagnostics.

Spinal Cord Malakoplakia Mimicking a Spinal Cord Tumor : The First Case Report.

Malakoplakia is a rare chronic inflammatory disease that has been rarely reported in the genitourinary tract, gastrointestinal tract, adrenal glands, skin, lungs, bone, and endometrium. Central nervous system malakoplakia is extremely rare, and even then, it has only been reported in the cerebrum and cerebellum. A definite diagnosis of malakoplakia depends on microscopic detection of Michaelis-Gutmann bodies. We would like to present the case of a 61-year-old male who, after undergoing a liver transplant and receiving prolonged antibiotic treatment for Escherichia coli bacteremia, presented with quadriparesis and gait disturbance. The clinical and radiologic appearance of malakoplakia mimics that of malignant tumor. This is a condition with no established appropriate treatment and presents challenges due to its spinal cord location. However, this case presents a case of spinal cord malakoplakia and may provide newly differential diagnosis of an intramedullary mass in the spinal cord.

Prevalence and risk factors for haematogenous periprosthetic joint infection during Staphylococcus aureus bacteraemia

Background Staphylococcus aureus bacteraemia (SAB) may lead to periprosthetic joint infections (PJI) via haematogenous spread of bacteria to the joint. Due to the risk of PJI, patients with SAB and prosthetic joint are recommended prolonged antibiotic treatment. The aim of the study was to assess the risk of PJI during SAB, and to evaluate if short treatment duration affects outcomes in patients with uncomplicated SAB and prosthetic joints without clinical signs of PJI. Methods Patients with growth of S. aureus in blood cultures were cross-referenced against the Swedish Arthroplasty register to identify patients with prosthetic hip or knee joints at the time of SAB. Medical records were reviewed to identify PJI at the time of SAB and during a 6-month follow-up period. Results Out of 400 patients with SAB and a prosthetic joint, 281 met all eligibility criteria and were included in the study. Of the included participants, 35 (12%) had a haematogenous PJI. Younger age and presence of multiple prosthetic joints were associated with an increased risk of PJI. Of the 247 patients without signs of PJI at the initial SAB episode, 118 patients (48%) had an uncomplicated infection and received short total antibiotic treatment (median 15 days, IQR 13-17). The risk of PJI during the follow-up period was low (<1%) and similar in the uncomplicated group compared to patients with complicated SAB that received longer antibiotic treatment (median 29 days, IQR 15-70). Conclusion The prevalence of haematogenous PJI was lower than previously reported. Our data do not support prolonged antibiotic treatment in patients with SAB and prosthetic joints without clinical signs of PJI.

The efficacy of prolonged antibiotic prophylaxis in total breast reconstruction with Autologous Fat Transfer (AFT): A retrospective cohort study

BackgroundAutologous fat transfer (AFT) is increasingly adopted as another total breast reconstruction option. The aim of this study is to investigate the efficacy of prolonged antibiotic treatment on the onset of surgical site infections in patients treated with AFT for total breast reconstruction. MethodsThis retrospective cohort study was conducted on patients who received AFT for total breast reconstruction, with antibiotic prophylaxis during their (multiple) AFT procedure(s) from 9 December 2020 to 10 October 2023. Patients were divided into two groups according to their prophylactic antibiotic regimen. The primary outcome was analysed as the cumulative incidence, the relative risk (RR), the absolute risk reduction (ARR), and the number needed to treat (NNT). For the secondary outcome, a multilevel logistic regression analysis was performed. Results765 surgeries in 205 patients were analyzed. 624 surgeries on 168 patients had perioperative antibiotic prophylaxis in combination with post-operative antibiotic prophylaxis was administered (group 1). 141 surgeries on 37 patients had only perioperative antibiotic prophylaxis administered (group 2). The RR was 0.68 (95%CI 0.14 – 3.31) of a surgical site infection (SSI) when receiving peri- and postoperative antibiotic prophylaxis in comparison to treatment with only perioperative prophylaxis. The ARR was 0.46% (95%CI -1.40 – 2.32) with a NNT of 219 patients. ConclusionProlonged antibiotic prophylaxis is ineffective for patients who receive total breast reconstruction with AFT. This study showed no statistically significant difference in SSIs of the reconstructed breast after receiving prolonged antibiotic treatment in comparison to single shot peri-operative antibiotic prophylaxis.

Rifampin-resistant periprosthetic joint infections are associated with worse functional outcome in both acute and chronic infection types

Periprosthetic joint infections (PJI) pose a significant challenge in orthopaedic surgery, often requiring extensive surgical debridement and prolonged antibiotic treatment to eliminate the causative pathogens. Rifampin, known for its potent activity against biofilms, has been crucial in managing PJI by penetrating and disrupting these formations, thereby improving treatment efficacy. In this sense, antibiotic protocols lacking rifampin have shown increased failure rates. Consequently, the development of rifampin resistance could severely influence the prognosis of PJI. The aim of this clinical study was to assess how rifampin resistance affects the functional outcome in patients with PJI. In this single-centre comparative cohort study, we systematically documented all patients who presented with a PJI during the period spanning from 2018 to 2020. Two distinct groups were established for the study: Group 1 comprised 35 patients with a PJI caused by rifampin-susceptible pathogens and group 2 consisted of 28 patients with PJI caused by rifampin-resistant pathogens. A total of 63 patients (34 females) with a mean age of 68 years and a mean follow up of 37 months were included. The examination of patient-specific parameters did not reveal any identified risk factors as influential. Patients with a rifampin-resistant pathogen underwent a greater number of surgical revisions (6.9 ± 5.1 compared to 3.59 ± 3.39, p = 0.0011) and had extended durations of antibiotic treatment (p = 0.0052). The results of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score revealed significant differences in clinical outcome between both groups in every domain, even when stratified by acute and chronic entities. In total the WOMAC increased significantly from 21.57 ± 14.9 points in group 1 to 71.47 ± 62.7 points in group 2 (p < 0.001). The higher failure rates observed in group 2 were not statistically significant (p = 0.44). The current study demonstrates that PJI caused by rifampin-resistant bacteria are associated with a significantly worse functional outcome in both acute and chronic infection types without significantly affecting total failure rates.

A Multi-Center Retrospective Observational Analysis of Three-Year Experience of Our Protocol for Prevention and Monitoring of Surgical Site Infections in Implant-Based Breast Reconstruction.

With the rise in the mastectomy rate, the number of patients who choose to undergo postmastectomy reconstruction has been increasing, and implant-based procedures are the most performed methods for postmastectomy breast reconstruction. Among the possible complications, the most feared is the loss of reconstruction. It can be related to several reasons, but one of the most common is infection of the implant, which can lead to prolonged antibiotic treatment, undesired additional surgical procedures, increased incidence of capsular contracture, and unsatisfactory aesthetics results, with a huge psychological impact on patients. The primary intent of this study is to analyze the status of infection rates at our institution and evaluate the effectiveness of our prevention protocol since its introduction. Secondly, we compared data of the surgical site infections (SSIs) after implant-based breast reconstruction at Trieste Hospital, where the protocol has been employed since 2020, and in another center, where plastic surgeons of our team are involved, with different prevention procedures. We enrolled 396 female patients, who underwent implant-based breast reconstruction, using definitive mammary implants or breast tissue expanders, with or without ADM (acellular dermal matrix), both for breast cancer and risk-reducing surgery in BRCA1/2 patients. Patients treated at the Hospital of Trieste, with the use of the prevention protocol, were considered the experimental group (group 1), while patients treated in Gorizia by the same breast team with standardized best-practice rules, but without the use of the prevention protocol, were considered the control group (group 2). Infected patients were 5 in the first group (1.7%) and 8 in the second one (7.9%), with a global infection rate of 3.2%. After the introduction of our prevention protocol, we faced a lower incidence of infection after breast surgery with implants or tissue expanders.

Characteristics of Bacteria in Urine and Stones from Patients Treated with Percutaneous Nephrolithotomy and Association with Postoperative Infection.

The purpose of this study was to identify bacterial differences between urine cultures (UC) and stone cultures (SC) in patients with complex kidney stones and to determine any correlation with post-percutaneous nephrolithotomy Systemic Inflammatory Response Syndrome (SIRS). Perioperative data of 1055 patients with complex kidney stones treated with first-stage Percutaneous Nephrolithotomy (PCNL) from September 2016 until September 2021 were included. Preoperative mid-stream urine samples and surgically obtained stone material were subjected to bacterial culture and antibiotic sensitivity tests. Preoperatively, antibiotic usage was determined by the UC or local bacterial resistance patterns. After PCNL treatment, antibiotic selection was guided by stone bacterial culture result and clinical symptoms. The effect of different preoperative antibiotic regimens based on urine cultures and postoperative antibiotic treatment based on stone cultures were assessed. Positive stone cultures (SC+) were significantly more common than positive urine cultures (UC+) (31.9% vs 20.9%, p < 0.05). Escherichia coli (E. coli) was the most common uropathogen in both urine (54.3%) and stones (43.9%). The difference was statistically significant (p < 0.05). Moreover, UC+SC-, UC-SC+, UC+SC+, and preoperative serum creatinine were independent risk factors of postoperative SIRS. The incidence of SIRS in the UC+SC+ patients with different bacteria in stones and urine (51.6%) was higher than that in other culture groups. The antibiotic resistance of E. coli inside the stone was increased when prolonged preoperative antibiotics were administered to UC+ patients. The bacterial spectrum and positive outcome of culture in urine and stones were significantly different. The incidence of postoperative SIRS was highest in patients with UC+SC+ but with different bacteria strains. Prolonged pre-surgical antibiotic treatment apparently induced higher drug resistance for bacteria inside the stone.

Adaptive attenuation of virulence in hypervirulent carbapenem-resistant Klebsiella pneumoniae.

The emergence of nosocomial infections caused by hypervirulent and carbapenem-resistant K. pneumoniae (hv-CRKP) has become a significant public health challenge. The genetic traits of virulence and resistance plasmids in hv-CRKP have been extensively studied; however, research on the adaptive evolution strategies of clinical strains inside the host was scarce. This study aimed to understand the effects of antibiotic treatment on the phenotype and genotype characteristics of hv-CRKP. We investigated the evolution of hv-CRKP strains isolated from the same patient to elucidate the transition between hospital invasion and colonization. A comparative genomics analysis was performed to identify single nucleotide polymorphisms in the rmpA promoter. Subsequent validation through RNA-seq and gene deletion confirmed that distinct rmpA promoter sequences exert control over the mucoid phenotype. Additionally, biofilm experiments, cell adhesion assays, and animal infection models were conducted to illuminate the influence of rmpA promoter diversity on virulence changes. We demonstrated that the P12T and P11T promoters of rmpA possess strong activity, which leads to the evolution of CRKP into infectious and virulent strains. Meanwhile, the specific sequence of polyT motifs in the rmpA promoter led to a decrease in the lethality of hv-CRKP and enhanced cell adhesion and colonization. To summarize, the rmpA promoter of hv-CRKP is utilized to control capsule production, thereby modifying pathogenicity to better suit the host's ecological environment.IMPORTANCEThe prevalence of hospital-acquired illness caused by hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) is significant, leading to prolonged antibiotic treatment. However, there are few reports on the phenotypic changes of hv-CRKP in patients undergoing antibiotic treatment. We performed a comprehensive examination of the genetic evolutionary traits of hv-CRKP obtained from the same patient and observed variations in the promoter sequences of the virulence factor rmpA. The strong activity of the promoter sequences P11T and P12T enhances the consistent production of capsule polysaccharides, resulting in an invasive strain. Conversely, weak promoter activity of P9T and P10T is advantageous for exposing pili, hence improving bacterial cell attachment ability and facilitating bacterial colonization. This finding also explains the confusion of some clinical strains carrying wild-type rmpA but exhibiting a low mucoid phenotype. This adaptive alteration facilitates the dissemination of K. pneumoniae within the hospital setting.

Evaluating antibiotic prophylaxis adherence: Implications for surgical site infections and wound care management

AimThis study aimed to evaluate adherence to an antibiotic prophylaxis protocol and its impact on incidence of surgical site infection (SSI). Materials and methodA prospective observational cohort study was conducted at a teaching hospital in São Paulo, Brazil, from September to November 2015. The population were adults who underwent surgery with surgical antibiotic prophylaxis. The main outcomes measured were incidence of SSI at 30-days postoperatively, protocol adherence and surgical wound complications. STROBE guidelines were followed. ResultsAmong the 527 participants recruited, a 30-day follow-up was completed by 78.7 % (n = 415). Within this cohort, 57.6 % were females aged over 60 years (36.4 %). The incidence of SSI stood at 9.4 % (n = 39), with dehiscence being the most prevalent complication at 64.1 % (n = 25), followed by increased exudate at 51.3 % (n = 20). Notably, full adherence to the antibiotic prophylaxis protocol was low at 1.7 % (n = 7). The study observed a 60 % increased risk of SSI for every protocol mistake made. Alarmingly, 17.8 % (n = 74) of participants received antibiotic treatment exceeding the stipulated protocol duration. The overall mortality rate stood at 13.5 % (n = 56), with 1 % (n = 4) of these deaths attributed to SSI. ConclusionThere is a pressing global necessity to enhance antibiotic management, as underscored by this study's revelation of low adherence to the antibiotic prophylaxis protocol. This lack of adherence correlated with a notable incidence of SSI and subsequent wound complications. Nearly 20 % of participants received prolonged antibiotic treatment. Adhering strictly to the protocol could substantially impact SSI-related outcomes and enhance global antibiotic management.

Prolonged Antibiotic Use in Gulf War Chronic Multisymptom Illness Induces Renal Fibrosis-Like Pathology Associated with microRNA-21-Mediated PTEN Inhibition

Gulf War veterans afflicted with chronic multisymptom Illness (GWI) often experience unexplained, debilitating symptoms, including microbiome dysbiosis, gastrointestinal and neuroinflammation. Prolonged antibiotic treatments, especially of fluoroquinolone class are commonly employed in these veterans, raising concerns about their potential side effects. To date, no studies have investigated the effects of Gulf War (GW) chemicals- Pyridostigmine bromide (PB) and insecticide, permethrin exposures on renal dysfunction in the veterans. Therefore, this study aimed to investigate the impact of prolonged antibiotic exposure on renal pathology in GWI and to elucidate the underlying molecular mechanisms leading to renal dysfunction. In this study, we used a persistent Gulf War Illness (GWI) mouse model to study the combined effect of prolonged antibiotic regimen involving Neomycin and Enrofloxacin treatment for 5 months (20 weeks). Our results showed that prolonged antibiotic treatment exacerbated renal inflammation leading to elevated levels of pro- inflammatory cytokines and significant activation of NF-κB signaling over Gulf war chemicals treated (GWI) mice (GWI). Further, we hypothesized the involvement of HMGB1 mediated RAGE activation leading to the inflammatory phenotype in the kidneys of GWI+ AB mice. We observed that prolonged antibiotic exposure in GWI- induced mice led to significant increased HMGB1-mediated RAGE activation compared to GWI mice, which was associated with increased TGF-β production in GWI+ AB mice. Furthermore, miR-21, whose expression is reported to be regulated by TGF-β is widely linked to renal fibrosis, was also significantly upregulated in antibiotic-treated GWI-induced mice. This upregulation was associated with decreased PTEN expression, a direct target of miR-21 in GWI+ AB mice over GWI- mice, resulting in the activation of the AKT signaling pathway and increased extracellular matrix (ECM) deposition in GWI+ AB mice. Furthermore, we examined the involvement of AKT signaling activation in the induction of Epithelial-Mesenchymal Transition (EMT) by assessing the immunoreactivity of α-SMA. The renal tissue of GWI+AB mice exhibited an elevated immunoreactivity of α-SMA, suggesting that the cells were undergoing transition from an epithelial to a mesenchymal state. In contrast, GWI- mice displayed no significant expression of α-SMA or increased fibronectin deposition, indicating that exposure to Gulf War chemicals alone was insuffcient to induce renal fibrosis-like pathology. These findings highlight the complex interplay between GWI, antibiotics, and renal pathology, emphasizing that prolonged antibiotic treatment in Gulf War Chronic Multisymptom Illness leads to renal fibrosis like- pathology by activating TGF- β dependent miR-21/ PTEN/ AKT signaling. This study was supported by VA Merit Award I01CX001923-01 awarded to Dr. Saurabh Chatterjee. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Antimicrobial De-Escalation in Critically Ill Patients.

Antimicrobial de-escalation (ADE) is defined as the discontinuation of one or more antimicrobials in empirical therapy, or the replacement of a broad-spectrum antimicrobial with a narrower-spectrum antimicrobial. The aim of this review is to provide an overview of the available literature on the effectiveness and safety of ADE in critically ill patients, with a focus on special conditions such as anti-fungal therapy and high-risk categories. Although it is widely considered a safe strategy for antimicrobial stewardship (AMS), to date, there has been no assessment of the effect of de-escalation on the development of resistance. Conversely, some authors suggest that prolonged antibiotic treatment may be a side effect of de-escalation, especially in high-risk categories such as neutropenic critically ill patients and intra-abdominal infections (IAIs). Moreover, microbiological documentation is crucial for increasing ADE rates in critically ill patients with infections, and efforts should be focused on exploring new diagnostic tools to accelerate pathogen identification. For these reasons, ADE can be safely used in patients with infections, as confirmed by high-quality and reliable microbiological samplings, although further studies are warranted to clarify its applicability in selected populations.

Perioperative antibiotic prophylaxis in the setting of cochlear implantation: a retrospective analysis of 700 cases

PurposePostoperative wound infections after cochlear implantation are rare but sometimes serious and can lead to explantation. Therefore, perioperative antibiotic administration is often recommended. However, in clinical practice, the type and duration of antibiotic prophylaxis varies between different centers. The aim of this study was to investigate the role of perioperative antibiotic prophylaxis in preventing postoperative complications.Methods700 patients who underwent cochlear implantation between 2007 and 2019 were retrospectively evaluated with regard to wound infections within the first 28 postoperative days. These were classified into major and minor complications. Data were analyzed using the IBM statistical program SPSS.ResultsIn 670 out of 700 patients the type and duration of perioperative antibiotic administration could be reconstructed from the records. Of these 67 patients (10%) received antibiotics as a single shot, 158 patients (23.6%) were treated with antibiotics for a period of 48 h, and 445 patients (66.4%) received prolonged antibiotic therapy for more than 72 h. In total 64 patients (9.5%) showed abnormalities in wound assessment within the first 28 postoperative days after implantation. Major infections (1.6%) were detected in 11 patients. Overall, there was no statistically significant difference in wound infection rates between the group receiving single-shot antibiosis and the group receiving 48 h prophylaxis or antibiotic treatment > 72 h (p = 0.46).ConclusionPatients receiving an antibiotic single shot do not appear to be at significantly increased risk for postoperative wound infections compared with patients with prolonged antibiotic treatment. Continuation of data collection across centers seems reasonable.

Antibiotic therapy impact on intravesical BCG therapy efficacy for high-risk localized bladder cancer treatment.

Intravesical Bacillus Calmettes-Guerin (BCG) instillations is the gold standard adjuvant treatment for high and very high-risk non-muscle-invasive bladder cancer (NMIBC). Antibiotics may be required to treat asymptomatic bacteriuria before instillations or to prevent side effects. By modifying the bladder microbiota and through its bactericidal action, it could modify the efficacy of BCG. This study evaluates the impact of antibiotics received during BCG-induction treatment on the oncological outcomes for high and very high risk NMIBC. We retrospectively included all patients who received a full induction regimen of BCG therapy between January 2017 and June 2022. Clinical and tumor characteristics as well as tolerability were collected. Recurrence-free survival (RFS) and progression-free survival (PFS) were compared according to the prescription of antibiotics, its type and duration. A total of 126 patients were included, 86.5% of the tumors were high risk and 13.5% very high risk. The median follow-up was 31 months (7-60). 36% of the patients received antibiotics during BCG-induction treatment (among which 44% received fluoroquinolones). 21.4% of patients had tumor recurrence. There was no difference in RFS (p=0.902) or PFS (p=0.88) according to the duration or the type of antibiotics received. The use of a prolonged antibiotic treatment (> 7 days) significantly increased the duration of the BCG-induction treatment from 35 to 41,5 days (p=0,049) and the median number of delayed treatments by 1,5 [0-4]. Neither the use of antibiotics nor their duration modified the risk of recurrence or the intensity of side effects in multivariate analysis. Antibiotics received during BCG-induction immunotherapy did not influence oncological short-term outcomes or intensity of side effects.

Discrepancy between IDSA and ESGBOR in Lyme disease: Individual participant meta-analysis in Türkiye.

The evidence on the prevalence of Lyme borreliosis (LB) is limited, but there is a suspicion of overdiagnosis of LB in recent years. We reviewed the LB diagnosis and treatment-related data in Türkiye, based on the Infectious Diseases Society of America (IDSA) 2020 and European Society of Clinical Microbiology and Infectious Diseases Study Group for Lyme Borreliosis (ESGBOR) 2018 guidelines. By detecting the disagreements between these two, we outlined the areas to be improved for future guidelines. We performed a literature search according to the PRISMA guidelines in PubMed, Ovid-Medline, Web of Science, Turkish Medline, Scopus, CINAHL, ULAKBIM TR Index, Google Scholar and Cochrane Library databases. We included the published cases in a database and evaluated according to IDSA and ESGBOR guidelines. We outlined the reasons for misdiagnoses and inappropriate uses of antibiotics. We included 42 relevant studies with 84 LB cases reported from Türkiye between 1990 and December 2022. Among 84 cases, the most common clinical findings were nervous system findings (n = 37, 44.0%), erythema migrans (n = 29, 34.5%) and ophthalmologic findings (n = 15, 17.9%). The IDSA 2020 and ESGBOR 2018 guidelines agreed on the diagnosis of 71 (84.5%) cases; there was an agreement that 31 cases (36.9%) were misdiagnosed and 40 cases (47.6%) were correctly diagnosed, and there was disagreement for 13 cases (15.5%). Serum immunoglobulin M (IgM), IgG measurements by ELISA and western blot were widely performed, and they were effective in definitive diagnosis merely when used according to guidelines. Inappropriate use of antibiotics was detected in 42 (50.0%) of cases which were classified in the following categories: incorrect LB diagnosis, inappropriate choice of antibiotic, inappropriate route of drug administration and prolonged antibiotic treatment. Overdiagnosis and non-adherence to guidelines is a common problem. The discordance between seroprevalence and clinical studies necessitates a consensus over the best clinical approach.

A Mini Review on Current Challenges and Opportunities in the Management of Bovine Mastitis

Bovine subclinical mastitis stands out as a significant challenge in the dairy industry, leading to substantial milk losses. The issue becomes more alarming as lactating cows frequently face severe infections caused by Staphylococcus aureus bacteria, resulting in detrimental udder damage. The conventional approach of combating such infections involves prolonged antibiotic treatments, contributing to the emergence of Antimicrobial Resistance (AMR) in cows. Compounding the issue, S. aureus bacteria can undergo modifications, transforming into the formidable Methicillin-Resistant S. aureus (MRSA). Addressing this pressing concern requires exploring alternative solutions, and one promising avenue lies in the realm of medicinal plants. Leveraging the inherent antibacterial properties of phytochemicals found in various medicinal plants could offer a sustainable and effective approach to managing bovine mastitis. Not only do these botanical remedies provide a potential solution to the challenges posed by conventional antibiotic treatments, but they also offer a more environmentally friendly and holistic approach to safeguarding the health of dairy cows and preserving milk production in the industry.

In vitro activity of levonadifloxacin, the active drug of orally administered prodrug alalevonadifloxacin against bloodstream isolates of Burkholderia pseudomallei

Background and objectiveEradication of Burkholderia pseudomallei infections requires prolonged antibiotic treatment indicating microbiological and pharmacokinetic limitations of current options. Methods and resultsLevonadifloxacin, a novel benzoquinolizine-fluoroquinolone available intravenously and orally, showed greater activity than ciprofloxacin (MICs, 0.25 to 2 versus 0.25–8 mg/L) and comparable to doxycycline against 50 B.pseudomallei isolates. In time-kill assay, levonadifloxacin exerted rapid ∼3 log10 reduction while doxycycline was bacteriostatic. ConclusionLevonadifloxacin merits further investigations as a potential treatment option for B. pseudomallei infections.

Infectious keratitis following corneal transplantation: A long-term cohort study.

To assess the long-term incidence and risk factors for post-keratoplasty infectious keratitis (IK), associated ocular pathogens, and antibiotic resistance profiles. Cohort study including 2553 consecutive penetrating, endothelial, and anterior lamellar keratoplasties performed between 1992 and 2020. Medical and microbiological records of patients clinically diagnosed with IK were retrospectively reviewed. cumulative incidence of IK, infectious agent species, and antibiotics resistance profiles. The average follow-up time after transplantation was 112 ± 96 months. Eighty-nine IK episodes were recorded; microbiological tests were positive in 55/89 (62%). The cumulated incidence of postoperative IK was 5.50%/10.25% at 10/20 years. The occurrence of at least one episode of IK after transplantation was associated with lower graft survival in the long term (p < 0.0001). Rejection risk (adjusted Hazard Ratio, 2.29) and postoperative epithelial complications (HR, 3.44) were significantly and independently associated with a higher incidence of postoperative IK. Infectious agents included 41 bacteria, 10 HSV, 6 fungi, and 1 Acanthamoeba. The rate of antibiotic resistance was 0% for vancomycin, 13% for fluoroquinolones, 20% for rifamycin, 59% for aminoglycosides, and 73% for ticarcillin. In 41% of cases, patients were under prophylactic topical antibiotics before the infectious episode. Topical antibiotics were significantly associated with increased resistance to penicillin, carbapenems, and aminoglycosides. IK (mainly bacterial) is a frequent complication of corneal transplantation in the long term. Vancomycin and fluoroquinolones can be considered as first-line treatments. Prolonged postoperative antibiotic preventive treatment is not advisable as it may increase antibiotic resistance.

Prolonged Antibiotic Use in a Preclinical Model of Gulf War Chronic Multisymptom-Illness Causes Renal Fibrosis-like Pathology via Increased micro-RNA 21-Induced PTEN Inhibition That Is Correlated with Low Host Lachnospiraceae Abundance.

Gulf War (GW) veterans show gastrointestinal disturbances and gut dysbiosis. Prolonged antibiotic treatments commonly employed in veterans, especially the use of fluoroquinolones and aminoglycosides, have also been associated with dysbiosis. This study investigates the effect of prolonged antibiotic exposure on risks of adverse renal pathology and its association with gut bacterial species abundance in underlying GWI and aims to uncover the molecular mechanisms leading to possible renal dysfunction with aging. Using a GWI mouse model, administration of a prolonged antibiotic regimen involving neomycin and enrofloxacin treatment for 5 months showed an exacerbated renal inflammation with increased NF-κB activation and pro-inflammatory cytokines levels. Involvement of the high mobility group 1 (HMGB1)-mediated receptor for advanced glycation end products (RAGE) activation triggered an inflammatory phenotype and increased transforming growth factor-β (TGF-β) production. Mechanistically, TGF-β- induced microRNA-21 upregulation in the renal tissue leads to decreased phosphatase and tensin homolog (PTEN) expression. The above event led to the activation of protein kinase-B (AKT) signaling, resulting in increased fibronectin production and fibrosis-like pathology. Importantly, the increased miR-21 was associated with low levels of Lachnospiraceae in the host gut which is also a key to heightened HMGB1-mediated inflammation. Overall, though correlative, the study highlights the complex interplay between GWI, host gut dysbiosis, prolonged antibiotics usage, and renal pathology via miR-21/PTEN/AKT signaling.

Therapeutic Drug Monitoring of Dalbavancin in Real Life: A Two-Year Experience.

Dalbavancin is a long-acting lipoglycopeptide that is registered for the treatment of acute bacterial skin and skin structure infections, and it is also increasingly used for infections that require prolonged antibiotic treatment. Here, we present the results from the first 2 years of a service set up in December 2021 for the therapeutic drug monitoring (TDM) of dalbavancin in clinical settings. In particular, we compared the trough concentration (Cmin) to maximum concentration (Cmax) in patients with osteoarticular infections receiving prolonged treatment with dalbavancin. Log-linear regression models were used to estimate the timing of dalbavancin administration with the goal of maintaining Cmin concentrations of >8 mg/L in the two TDM-based strategies. From December 2021 to November 2023, 366 TDMs of dalbavancin from 81 patients were performed. The Cmin and Cmax concentrations of dalbavancin ranged from 4.1 to 70.5 mg/L and from 74.9 to 995.6 mg/L, respectively. With log-linear regression models, we estimated that each injection should be administered every 42-48 days to maintain the Cmin concentrations. Out of the 81 patients, 37 received at least three doses of dalbavancin for the treatment of osteoarticular infections. Despite there being no significant differences in the days of dalbavancin treatment (130 ± 97 versus 106 ± 102 days), the patients in the Cmax-based TDM group received a significantly lower number of dalbavancin injections (5.2 ± 1.8 versus 7.3 ± 2.6 injections, p = 0.005), and they were administered over a longer period of time (40 ± 10 versus 29 ± 14 days, p = 0.013) than in the Cmin-based TDM group. In conclusion, Cmax-based TDM was associated with a significant reduction in the inter-individual variability of dalbavancin concentrations and lower drug dosing frequency than those of Cmin-based TDM. This approach could, therefore, favor a more rational and targeted use of dalbavancin in patients requiring prolonged treatment.

Analysis of In-Patient Evolution of Escherichia coli Reveals Potential Links to Relapse of Bone and Joint Infections.

Bone and joint infections (BJIs) are difficult to treat and affect a growing number of patients, in which relapses are observed in 10-20% of case. These relapses, which call for prolonged antibiotic treatment and increase resistance emergence risk, may originate from ill-understood adaptation of the pathogen to the host. Here, we investigated 3 pairs of Escherichia coli strains from BJI cases and their relapses to unravel adaptations within patients. Whole-genome comparison presented evidence for positive selection and phenotypic characterization showed that biofilm formation remained unchanged, contrary to what is usually described in such cases. Although virulence was not modified, we identified the loss of 2 virulence factors contributing to immune system evasion in one of the studied strains. Other strategies, including global growth optimization and colicin production, likely allowed the strains to outcompete competitors. This work highlights the variety of strategies allowing in-patient adaptation in BJIs.