Systemic Prophylaxis Research Articles

ANTIBACTERIAL THERAPY IN SEPSIS PATIENTS

Today, sepsis, the cause of which is purulent-inflammatory processes of soft tissues, accounts for more than 45% of cases. In most multidisciplinary hospitals, the frequency of gram-positive and gram-negative sepsis is approximately the same. Antibacterial therapy (ABT) is the most important component of the complex therapy of sepsis, and early adequate empiric ABT leads to a decrease in mortality and the frequency of complications. ABT of sepsis at the beginning of treatment, in most cases, is empirical in nature, but it should be remembered that taking the material for microbiological research must be done before the start of antibacterial therapy! According to the principles adopted in the guideline "Sepsis - 3", the use of antibiotics for the treatment of sepsis is a necessary component, the effectiveness of which cannot be doubted. It should be remembered that a delay in the appointment of an antibacterial drug to patients with sepsis and septic shock for 1 hour leads to an increase in the risk of death of the patient by 7,6%. Empiric ABT should be initiated with a broad-spectrum regimen of one or more antibiotics in patients with sepsis or septic shock to cover all possible pathogens (including bacterial, possibly fungal, or viral). Empiric ABT should be narrowed after identification of the pathogen and determination of its sensitivity and/or when adequate clinical improvement is registered. There are no indications for long-term systemic antibacterial prophylaxis in patients with severe forms of inflammatory conditions of non-infectious origin (for example, severe pancreatitis, burns). Measurement of procalcitonin levels can be used to shorten the duration of antibacterial therapy in patients with sepsis. Rapid interpretation of the severity of the infectious process can be performed using ACCP/SCCM sepsis diagnostic criteria, organ dysfunction criteria (gSOFA, SOFA, MODS) or rapid procalcitonin test. Microbiological diagnosis of sepsis is the main factor in prescribing adequate ABT regimens. In the case when the same microorganism is released from the probable source of infection and from the peripheral blood, its etiological role in the development of sepsis should be considered as evidential. The standard for testing blood for sterility is the collection of material from two peripheral veins with an interval of up to 30 minutes, while blood from each vein must be collected in two vials. It is not permissible to take blood from the catheter! Building an ABT algorithm taking into account the etiology and characteristics of resistance of microorganisms to antibacterial drugs is the most optimal approach. Тoday, the optimal regimen of empiric ABT of sepsis with PON is carbapenems - as drugs that have the widest spectrum of action and to which the lowest level of resistance is observed among intra-hospital strains of gram(-) bacteria. In some cases, an alternative to carbapenems is cefepime, ceftaroline, protected by antipseudomonas β-lactams (cefaperazone/sulbactam, piperacillin/tazobactam) and "respiratory" fluoroquinolones. In cases of ineffectiveness of the indicated regimens of ABT, the feasibility of additional appointment of glycopeptides (vancomycin, teicoplanin or linezolid), as well as systemic antimycotics (fluconazole) should be evaluated. The latter should also be prescribed after 7-10 days after the start of ABT in a prophylactic dose of 150 mg per week.

Invasive Fungal Disease in Pediatric Heart Transplant Recipients

Abstract Background The epidemiology of IFD following pediatric heart transplantation (pHT) is poorly characterized. We sought to evaluate use of antifungal prophylaxis and describe the epidemiology of IFD in pHT at two large children’s hospitals. Methods We performed a retrospective cohort study of pediatric and young adult (≤21 years) patients undergoing heart transplantation at Cincinnati Children’s Hospital Medical Center (CCHMC) and Children’s Hospital of Philadelphia (CHOP) between 2012 and 2021. We recorded demographic, clinical, medication, and laboratory data for pHT patients through 12 months post-transplant. We identified use of topical (oral nystatin) and systemic antifungal prophylaxes in the peri-transplant period (7 days prior through 14 days following transplant) and analyzed if certain transplant variables were associated with the administration of systemic antifungals during this period using rank sum and chi squared tests. Applying published definitions, we quantified the incidence of proven and probable IFD and explored the characteristics of these cases. Results A total of 201 patients underwent heart transplant at CCHMC and CHOP. The majority were male (60.2%), White (66.7%), and not Hispanic or Latino (88.1%). Median age at time of transplant was 7.4 years (IQR 0.9-14.2). During the peri-transplant period, 143 (71.1%) patients received oral nystatin and 37 (18.4%) received systemic antifungal prophylaxis, not including PJP prophylaxis. 41 individuals (20.4%) were not on any antifungal prophylaxis throughout this period. Delayed chest closure was significantly associated with the administration of systemic antifungals (p<0.001) while several other variables (age, hospital, immunosuppression medication, ECMO/LVAD pre-transplant) were not. In total, 8 patients (4%) developed proven (n=5) or probable (n=3) IFD. In our cohort, the incidence rate of proven/probable IFD in the first year post-transplant was 44.8 per 1000 patient-years. The characteristics of these cases are shown in Table 1. Time from pHT to IFD ranged from 11 days to 196 days (median time = 25.5 days). All cases of proven IFD occurred within 28 days of transplant. In three cases of proven/probable IFD, patients were receiving a systemic antifungal or PJP prophylaxis in the seven days prior to IFD onset. Two cases met the definition of probable IFD but the infections resolved without directed therapies. Four patients with proven IFD died within 1 year following transplant, although in only 3 cases was IFD a contributing factor. The one-year all-cause mortality rate among pHT patients with proven/probable IFD (50%) was higher than that in pHT patients without IFD (10.3%; Fisher’s exact p=0.008). Conclusion Over a 10-year period at CCHMC and CHOP, 4% of pHT patients developed proven or probable IFD within one-year post-transplant. All proven IFD cases occurred within a month of transplant while probable cases occurred more than 100 days post-transplant. Delayed chest closure was significantly associated with the administration of systemic antifungal prophylaxis. Patients with proven IFD had poor outcomes despite receipt of appropriate antifungal treatment. Given the low incidence of IFD at these two centers, we were unable to evaluate risk factors for IFD in this population and so larger studies would be needed.

Intraosseous regional antibiotic prophylaxis in total joint arthroplasty (TJA): Systematic review and meta-analysis

BackgroundA major catastrophic adverse event after total joint arthroplasty surgery (TJA) is the periprosthetic joint infection (PJI). In the recent years, regional antibiotic prophylaxis has gained momentum as a novel infection control strategy in total knee arthroplasty (TKA), with different purported benefits over systemic administration. The current article was planned to comprehensively review the available evidence in literature; as well as compare the safety and effectiveness of intraosseous (IO) antibiotic prophylaxis with systemic prophylaxis in patients undergoing TJA. MethodsAn independent database (5 databases: Pubmed, Scopus, Embase, Web of science and Cochrane library) search was performed (on January 1, 2024) using suitable key words [PROSPERO (registration number: CRD42023458219)]. All randomised controlled trials (RCT), prospective or retrospective studies reporting data on intraosseous vancomycin or other antibiotics during arthroplasty for prophylaxis of PJI were considered. Studies not pertaining to the topic of interest or non-clinical trials were excluded. The evaluated outcome parameters included PJI incidence, systemic antibiotic levels, minimal inhibitory concentrations, local antibiotic concentrations achieved in soft tissues (or fat) and bone; and associated complications. While the “risk of bias” was evaluated using ROB-2 tool and MINORS criteria; LibreOffice version (v)7.5.6 was utilized for data management. OpenMeta-analyst v5.26.14 and RevMan v5.4 software were employed for meta-analysis. ResultsFollowing our literature search, 11 studies (1 prospective series, 6 RCT and 4 retrospective studies) were finally identified. Based on our meta-analysis, there was statistically higher antibiotic concentration in the bone [meandifference(MD):25.12 μg/g;95%CI:10.32,39.91;z=3.33,p = 0.0009] and local fat tissues [MD:22.01 μg/g;95%CI:1.71,32.30;z=4.19,p < 0.0001) following IO prophylaxis, as compared with the systemic drug administration. IO prophylaxis was also associated with a significant reduction in prosthetic joint infections (PJI; April 1633 and 25/2213 patients developed PJI in IO and systemic prophylaxis groups, respectively; p = 0.006). There was significant difference in gram-positive infections between IO and systemic prophylaxis groups (2/1123 and 13/1753 g + ve infections in IO and systemic prophylaxis groups, respectively; p = 0.05). Our review and meta-analysis revealed no substantial difference in complications amongst the groups (p = 0.66). ConclusionIO antibiotic prophylaxis appears to be an effective and safe strategy in patients undergoing TJA. IO access provides substantially enhanced antibiotic elution into the local tissues (bone and soft tissues); and consequently, results in reduced of PJI rates after TJA (in comparison with conventional systemic antibiotic prophylaxis).

Clinical Trial Protocol for Porcine Islet Xenotransplantation in South Korea.

Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.

Advanced Antimicrobial and Anti-Infective Strategies to Manage Peri-Implant Infection: A Narrative Review.

Despite reductions in bacterial infection and enhanced success rate, the widespread use of systemic antibiotic prophylaxis in implant dentistry is controversial. This use has contributed to the growing problem of antimicrobial resistance, along with creating significant health and economic burdens. The basic mechanisms that cause implant infection can be targeted by new prevention and treatment methods which can also lead to the reduction of systemic antibiotic exposure and its associated adverse effects. This review aims to summarize advanced biomaterial strategies applied to implant components based on anti-pathogenic mechanisms and immune balance mechanisms. It emphasizes that modifying the dental implant surface and regulating the early immune response are promising strategies, which may further prevent or slow the development of peri-implant infection, and subsequent failure.

Efficacy of antibiotic prophylaxis for reducing capsular contracture in prosthesis-based breast surgery: a systemic review and meta-analysis.

Antibiotics Prophylaxis to prevent capsular contracture in prosthesis-based breast surgery is common in clinical practice. However, there is currently a dearth of high-quality evidence concerning the effectiveness of antibiotic usage in this field. To identify all pertinent studies prior to January 2023, a comprehensive literature search was conducted in the PubMed, Embase, Web of Science, Cochrane Library, and Medline databases. The extracted data was then subjected to meta-analysis. Fourteen studies were retained in the analysis. According to the results, perioperative antibiotic prophylaxis did not reduce the risk of capsular contracture (RR 1.15, 95% CI 0.82-1.59, p = 0.55) or surgical-site infection (RD 0.01, 95% CI - 0.01 to 0.03, p = 0.59) compared to nonantibiotic prophylaxis. There was no statistically significant difference between extended antibiotic prophylaxis and perioperative antibiotic prophylaxis in terms of preventing capsular contracture, whether calculated by patient numbers (RD 0.01, 95% CI - 0.01 to 0.02, p = 0.87) or by total procedures (RD 0.00, 95% CI - 0.00 to 0.01, p = 0.88), or controlling surgical-site infection (RR 1.05, 95% CI 0.77-1.44, p = 0.27). Additionally, topical antibiotic irrigation did not decrease the risk of infection (RR 0.61, 95% CI 0.34-1.08, p = 0.29) and capsular contracture, regardless of patient number (RR 0.41, 95% CI 0.27-0.63, p = 0.18) or total number of procedures (RR 1.29, 95% CI 0.73-2.28, p < 0.01). Current evidence revealed that both systemic and topical antibiotic prophylaxis may not provide benefits in preventing capsular contracture in prosthesis-based breast surgery. When the occurrence of surgical-site infections is minimized to the greatest extent, the administration of additional antibiotics for reducing capsular contracture should be carefully and judiciously considered.

Limitations of antifungal prophylaxis in preventing invasive Candida surgical site infections after liver transplant surgery.

Invasive primary Candida surgical site infections (IP-SSIs) are a common complication of liver transplantation, and targeted antifungal prophylaxis is an efficient strategy to limit their occurrence. We performed a retrospective single-center cohort study among adult single liver transplant recipients at Duke University Hospital in the period between 1 January 2015 and 31 December 2020. The study aimed to determine the rate of Candida IP-SSI according to the peri-transplant antifungal prophylaxis received. Of 470 adult single liver transplant recipients, 53 (11.3%) received micafungin prophylaxis, 100 (21.3%) received fluconazole prophylaxis, and 317 (67.4%) did not receive systemic antifungal prophylaxis in the peri-transplant period. Ten Candida IP-SSIs occurred among 5 of 53 (9.4%) micafungin recipients, 1 of 100 (1.0%) fluconazole recipients, and 4 of 317 (1.3%) recipients who did not receive antifungal prophylaxis. Our study highlights the limitations of antifungal prophylaxis in preventing invasive Candida IP-SSI after liver transplant surgery. We hypothesize that pathogen, host, and pharmacokinetic-related factors contributed to the occurrence of Candida IP-SSI despite antifungal prophylaxis. Our study reinforces the need for a risk-based, multi-pronged approach to fungal prevention, including targeted antifungal administration in patients with risks for invasive candidiasis and close monitoring, especially among patients with surgically complex procedures, with timely control of surgical leaks.

Antibiotic usage within cesarean section procedures in resourced-limited Kenya: A study of 23 facilities

Introduction: In Kenyan cesarean sections (CS), antibiotics play a crucial role in preventing surgical site infections. In Kenya, where maternal health care is a pivotal public health concern, understanding the efficacy and appropriateness of antibiotic prophylaxis in CS is crucial. This study seeks to address this gap by understanding antibiotic prophylaxis practices and the classes of antibiotics utilized for prophylaxis during CS in Kenya. Methods: We conducted a cross-sectional survey on infection prevention and control (IPC) practices by adapting the World Health Organization (WHO) IPC assessment framework. One component of this survey included questions on antibiotic prophylaxis for CS. Purposive sampling was used to identify 23 hospitals across seven districts in Kenya that provided CS. Results: All 23 facilities used a form of systemic antibiotic prophylaxis. Preoperative systemic antibiotic prophylaxis was used by 78.2%, and postoperative prophylaxis was universal. The mean duration of postoperative antibiotic prophylaxis was 3.87 days. Ceftriaxone (91.3%), metronidazole (82.6%), and gentamicin (26.1%) were the most common systemic antibiotics. In addition, 91.3% administered oral antibiotics postoperatively, with a mean duration of 5.6 days. Predominant oral antibiotics included metronidazole (82.6%), amoxicillin–clavulanate (60.9%), and ceftriaxone (13.0%). Conclusion: The antibiotic practices utilized within the Kenya setting do not follow either the American College of Obstetricians and Gynecologists (ACOG) or WHO recommendations. Both organizations recommend pre-CS administration of a first-generation cephalosporin 60 min before incision. This class of antibiotics is not used at any of the study sites. In addition, all of the study sites provide postantibiotic prophylaxis, which is not recommended by either ACOG or WHO for prophylaxis.

Comparing the Efficacy of Systemic Fluconazole and Oral Nystatin Prophylaxis for Prevention of Systemic Fungal Infections in Very Low Birth Weight (VLBW) Infants: A Randomized Clinical Trial

Comparing the Efficacy of Systemic Fluconazole and Oral Nystatin Prophylaxis for Prevention of Systemic Fungal Infections in Very Low Birth Weight (VLBW) Infants: A Randomized Clinical Trial

Effect of prolonged antibiotic prophylaxis on the occurrence of surgical site wound infection after instant breast reconstruction: A meta-analysis.

The purpose of the meta-analysis was to evaluate and compare the effects of prolonged antibiotic prophylaxis on the occurrence of surgical site wound infection after instant breast reconstruction. The results of this meta-analysis were analysed, and the odds ratio (OR) and mean difference with 95% confidence intervals (CIs) were calculated using dichotomous or contentious random- or fixed-effect models. For the current meta-analysis, 18 examinations spanning from 2009 to 2023 were included, encompassing 19 301 females with instant breast reconstruction. Systemic antibiotic prophylaxis had a significantly lower surgical site wound infection rate (OR, 0.85; 95% CI, 0.75-0.98, p = 0.02) compared with the standard of care after instant breast reconstruction in females. Topical antibiotic prophylaxis had a significantly lower surgical site wound infection rate (OR, 0.26; 95% CI, 0.13-0.52, p < 0.001) compared with the standard of care after instant breast reconstruction in females. The examined data revealed that systemic and topical antibiotic prophylaxis had a significantly lower surgical site wound infection rate compared with the standard of care after instant breast reconstruction in females. However, given that several examinations had a small sample size, consideration should be given to their values.

Does topical vancomycin prevent fracture-related infections in closed fractures undergoing open reduction and internal fixation? A randomised controlled trial

PurposeThe role of topical vancomycin in fracture-related infection (FRI) is debatable. Very few studies have reported their efficacy in open and high-risk extremity fractures. This study aimed to assess topical vancomycin's role in reducing FRI in closed fractures undergoing open surgical intervention with an implant. MethodsThis prospective randomized cohort study was carried out between February 2021 to January 2022. Patients with isolated closed fractures, who were planned for open reduction and internal fixation within 2 weeks from the time of injury were included for this study. The data collected included age, gender, socioeconomic status, mechanism of injury, diagnosis, Tscherne classification, and time interval to take up for surgery. Patients were randomized into the intervention and control groups using the block randomization technique. The control group received only systemic antibiotic prophylaxis, whereas the intervention group received topical application of vancomycin powder in the surgical wound alongside systemic antibiotic prophylaxis. The primary outcome measure was the incidence of FRI among these individuals. Clinical and radiological findings and culture reports (in cases with infection) were recorded during the post-operative period and at 6 weeks of follow-up. All relevant statistical calculations were done using STATA statistical/data analysis-parallel edition version 16.0 (StataCorp LLC). The quantitative variables like age and duration of the surgery were assessed for normalcy by Shapiro-Wilk W test. An independent samples t-test with equal variances was applied to the age data. Fisher's exact test was used for the analysis of the primary outcome measure (presence of FRI following surgery), and “Risk of FRI” and “Risk difference” between the 2 groups was calculated. The strength of the association between qualitative variables was assessed using the Fisher's exact and Chi-square tests, respectively. ResultsThere were 88 patients included in this study. No statistical significance was found about FRI between both groups (p = 0.494). At 6 weeks following surgery, no incidence of infection was observed in the intervention group. Two infections (4.5%) were found in the control group, with positive cultures reported in one of them but none in the treatment group. Radiologically, 15.9% of patients in the control group showed lysis around the implant compared to 2.3% in the intervention group. Impaired fracture healing was observed in 22.7% of patients in the intervention group compared to 15.9% in the control group. ConclusionApplying topical vancomycin in closed fractures undergoing open reduction and internal fixation does not significantly reduce the incidence of FRI until the end of 6 weeks following surgery.

Timing of Thrombosis with Myeloproliferative Neoplasm Diagnosis Among Veterans and Civilians

Rates of Arterial (AT) and Venous Thrombosis (VT) are increased in Veterans with Myeloproliferative Neoplasms (Vet-MPN), including Essential Thrombocythemia (ET), Polycythemia Vera (PV), and Primary Myelofibrosis (PMF), compared to matched controls (J Clin Oncology 2023 41:16_suppl, 7011). The timing of first AT or VT episode in Vet-MPNs remains undefined when compared to Civilians with MPN (Civ-MPN). These findings could elucidate optimal timing for risk mitigation strategies to prevent thrombotic complications and should help to determine duration of thrombotic risk and need for systemic anticoagulation prophylaxis. The Veterans Affairs Informatics and Computing Infrastructure (VINCI) database was queried from January 1, 2006 to January 26, 2023 to identify Vet-MPNs, AT, and VT through ICD-9 and -10 codes. This process yielded 2,752 Vet-MPN and 583,803 Veterans without MPN from Illinois, the state most representative of the US population. These cohorts were compared to data derived from a retrospective chart review of Civ-MPN cared for between January 1, 2019 to December 31, 2022, at MedStar Georgetown University Hospital and MedStar Washington Hospital Center. Service-Connected Exposures (SCE) to potential carcinogens among Veterans were verified through their duration and location of service. We subdivided time to first AT and VT from MPN diagnosis as follows: more than 3 months prior to MPN diagnosis, within 3 months of diagnosis, 3 months to 1 year post diagnosis, 1 to 5 years, and more than 5 years after MPN diagnosis. Mean data from various cohorts were analyzed utilizing Fisher's exact test. Vet-MPN experienced a statistically higher incidence of AT compared to Civ-MPN (p=.0019) and Civ-MPN experienced a statistically higher incidence of AT compared to Veterans without MPN (p=0.02) which served as a control. In contrast, there was a higher incidence of VT among both Vet- and Civ-MPN cohorts compared to Veterans without MPN (p&amp;lt;.0001) (Table 1). The mean ages at MPN diagnosis and onset of first AT were similar (≥63 years) in both Civ- and Vet-MPN. In contrast, the mean age of MPN diagnosis and age of first VT were considerably earlier for Civ-MPN (51 years) versus both Vet-MPN with VT and Veterans without MPN with VT (≥67 years). There was a higher prevalence of hypertension, hyperlipidemia, diabetes, heart failure, and smoking among Veterans with or without MPN compared to Civ-MPN with either AT or VT (Table 1). A trend toward statistical significance was observed for the presence of hypertension and hyperlipidemia (p=0.049 and p=0.02, respectively) in Vet-MPN compared to Civ-MPN, while Veterans without MPN had a statistically higher prevalence of hyperlipidemia (p=0.02) and heart failure (p=0.001) in AT. Notably, a trend toward statistical significance in VT was observed for the presence of diabetes among all Veterans with or without MPN compared to Civ-MPN (p=0.01 and p=0.007, respectively). There was a biphasic distribution in time to onset of first AT and VT in all Vet- and Civ-MPN cohorts (Figure 1). There was a higher cumulative incidence of first AT and VT in Vet-MPN at more than 3 months prior to MPN diagnosis compared to Civ-MPN with AT and VT (Figure 1). On the other hand, the Civ-MPN cohort had a late surge of first VT more than 5 years after MPN diagnosis compared to the other MPN cohorts. A biphasic distribution in time to onset of first AT and VT was also observed among the Vet-MPN cohort when stratified by SCEs from World War II, the Korean War, the Vietnam War, and the Gulf War. The vast majority of both AT and VT in Vet-MPN from all SCE examined experienced onset of thrombotic events more than 3 months prior to MPN diagnosis. Most VT in Gulf War Vet-MPN occurred within 3 months of MPN diagnosis. In conclusion, the predominant risk for developing thrombotic complications in MPN, particularly in Vet-MPN, occurs in a biphasic pattern, beginning more than 3 months prior to MPN diagnosis and becoming apparent again at more than 5 years after MPN diagnosis. These findings suggest that the MPNs convey an enduring hypercoagulability potential throughout the natural history of the disease. There appears to be an accelerated onset of thrombotic complications earlier in the course of disease in Vet-MPN, perhaps reflecting their SCE with toxic carcinogens. More work is necessary to determine epigenetic influences on MPN natural history.

Enhancing Surgical Outcomes: A Critical Review of Antibiotic Prophylaxis in Orthopedic Surgery.

The postoperative burden remains significant due to the possibility of prolonged hospitalization, escalated healthcare costs, and patient distress caused by postorthopedic surgicalsite infections (SSIs). Orthopedic surgery is likewise faced with a significant challenge posed by these conditions. A positive association has been observed between the presence of postorthopedic SSIs and heightened susceptibility to adverse health outcomes, along with elevated rates of morbidity and mortality. Systemic antibiotic prophylaxis (SAP) reduces the risk of acquiring an SSI. Closed fractures, open fractures, arthroplasty, and percutaneous fixation each possess distinct attributes that impact the data and antimicrobial therapy. When implementing SAP, it is crucial to strike a delicate equilibrium between maintaining effective antibiotic stewardship protocols and preventing the occurrence of SSIs. This practice effectively prevents both the incidence of negative consequences and the emergence of antibiotic resistance. The objective of this study was to examine the existing literature on the use of surgical antibiotic prophylaxis in orthopedic surgery and explore the potential consequences associated with the inappropriate administration of antibiotics.

Invasive fungal infections in pediatric patients with central nervous system tumors: novel insights for prophylactic treatments?

Invasive fungal disease (IFD) poses significant morbidity and mortality risks, especially in pediatric patients with neoplastic diseases. However, there is a notable lack of data concerning patients with central nervous system (CNS) tumors. Considering vulnerability factors to infections such as neutropenia, corticosteroids, chemotherapy, surgical interventions, and others, this study aims to evaluate the incidence of IFD in pediatric patients with CNS tumors and determine appropriate indications for prophylactic measures. This is a single-center, retrospective study conducted between 2011 and 2022 at the Pediatric Institute of Oncology (IOP-GRAACC-UNIFESP). A total of 38 cases of IFD were diagnosed in 818 children with CNS malignancies (4,6%). The mean age was 3.5 years (0.4-28y), with 22 (57.9%) male patients. Embryonal tumors (18/38, 47.3%) were the most prevalent CNS tumors, followed by low-grade gliomas (13/38, 34.2%). All episodes met the EORTC IFD criteria, and 36/38 (94.7%) were proven. Invasive yeast infections (33/36, 91.6%), predominantly Candida (30/33, 90.9%), were the most common diagnosis. In total, 25 patients (25/38, 65.8%) were receiving chemotherapy, with 13 of them having embryonal tumors. A total of 11 infants were in the Head Start scheme, resulting in a high prevalence of IFD in these group of patients (11/58, 18.9%). In total, 13 (13/38, 34.2%) patients underwent neurosurgery, mostly ventricular-peritoneal shunts revisions (10/13, 76.9%). Nine (9/38, 23.7%) were with prolonged use of corticosteroids, eight of them associated with neurosurgery. Routine systemic antifungal prophylaxis based solely on diagnosis is not recommended for low-risk cases. Evaluating patient- and treatment-specific risk factors is crucial in infants undergoing high-dose chemotherapy with expected neutropenia and in patients requiring prolonged corticosteroid therapy alongside neurosurgical procedures.

Structural and morphologic characteristics of nodular goiter in chronic iodine deficiency status

OBJECTIVES. Diffuse and nodular goiter are the most common thyroid gland (thyroid) diseases in children and adults living in iodine-deficient regions. Thyroid hormone potentiates progressive hypertrophy and hyperplasia of thyrocytes, with uneven proliferation of thyroid cells leading to nodule formation. Iodine deficiency, which promotes replication of thyroid follicular cells, also increases the incidence of TSH Receptor mutations, leading to receptor activation and autonomous functioning of follicles.AIM. To evaluate and describe ultrasound and cytologic thyroid nodes in the regions in Russia with proven iodine deficiency.MATERIALS AND METHODS. The study was conducted in regions with proven iodine deficiency in the Central and North Caucasian Federal Districts. Population of conditionally healthy adult volunteers (mean age — 47.5 years) was recruited as part of visiting events to screen for the occurrence of thyroid nodes.RESULTS. The results obtained indicate a high prevalence of multinodular colloid goiter in adult patients living in conditions of chronic iodine deficiency. In the Chechen Republic, the prevalence of nodular thyroid pathology was found in 64.5% (205/318) of cases, and in the Tula region — in 40.6% (116/286). In the studied sample the results of cytologic examination confirmed the presence of colloid thyroid masses in 97% (60/62) — Bethesda category II; in 3% (2/62) of patients nodular masses had Bethesda IV. Diffuse goiter prevalence in the examined population was 20.8%.CONCLUSIONS. A study indicates a high prevalence of iodine-deficient thyroid disease — multinodular colloid goiter in regions with proven chronic iodine deficiency. The wide prevalence of goiter with colloid and cystic components is confirmed by the cytologic examination with different ultrasound characteristics according to the EU-TIRADS classification. The obtained data correspond to the official statistics demonstrating high prevalence of nontoxic goiter in adults in the examined regions, which is an important argument confirming the need for systemic iodine prophylaxis.

Antibiotic Use in Adult Spine Deformity Surgery: Results From the AO Spine Surveillance of the Management of Patients With Adult Spine Deformity.

Cross-sectional international survey with literature review. To evaluate the evidence for these strategies and to understand the current trends in prophylactic antibiotic use during ASD surgery through an international survey. An online survey was conducted among international AO Spine members regarding the peri-operative management of patients with ASD. The details of perioperative systemic and topical antibiotic use were solicited. Descriptive data were summarized for the responding surgeons who perform at least 10 long-segment fusions of >5 levels extending to the pelvis annually. The literature supports the use of prophylactic antibiotic effective against gram positive organisms. The use of topical vancomycin remains debated, and there is limited evidence for topical tobramycin use. A total of 116 responses were received. 74 (64%) surgeons use topical vancomycin, most usually deep to the fascia only 45 (61%). The most usual dose used is 1-2g. 4 (3%) surgeons use topical tobramycin deep to fascia. Following surgery, 90 (78%) surgeons use prophylactic cephalosporin with 3 (3%) using cloxacillin, 5 (4%) using ciprofloxacin and 9 (8%) using vancomycin and 6 (5%) using clindamycin either in addition or alone. The present survey identifies a trend towards systemic and topical antibiotic prophylaxis primarily targeted at gram positive pathogens. The use of topical tobramycin, proposedly effective against gram negative infections, remains uncommon. There is a lack of consensus in the selection of perioperative antibiotic prophylaxis, thus a prospective study of the rates of infection with each strategy would be useful to inform guidelines.

Effect of a New Antibiotic Protocol Adopted by ASU Hospitals on Patients with Intra-Medullary Nailing of Femoral and Tibial Diaphyseal Fractures as Regard Post-Operative Infection

Background This study postulated that systemic antibiotic prophylaxis delivered preoperatively in intramedullary nailing of femur and tibia procedures significantly reduces the incidence of infection. Prophylactic antibiotics should be taken IV before skin incision by 30-60 minutes and no need for antibiotics more than 24 hours after operation. This protocol of antibiotics has multiple benefits such as saving a lot of money, decrease the risk of surgical site infection and decrease antibiotic resistance. Aim of the Work To assess the effect of antibiotic choice, duration on prevalence of surgical site infection among patients with intramedullary nailing of femoral and tibial fractures, and identify risk factors. Patients and Methods This study conducted on 50 cases of femoral and tibial fractures admitted from Al-Demerdash University Hospital in the period from June 2019 to December 2020 with age ranged from 18 to 56 years and with mean ± SD of 28.14 ± 10.14. This study was based on the antibiotic protocol adopted by Ain Shams University Hospitals that we give first generation cephalosporin (zinol) for all patient undergoing intramedullary nailing of femur and tibia, 30 – 60 minutes before skin incision and for 24 hours post-operative. Results The results of this study showed 1 case infected postoperative from 50 cases with a percentage of 2%, by this result we found that by studying the risk factors for infection there was no specific risk factor for infection except for obesity and diabetes. By studying of the results of application of our new antibiotic prophylaxis protocol in our hospital (Ain Shams University Hospitals) from the period from 6-2019 to 12-2020 the new protocol have the benefits of the following: Decrease of the total percentage of infection in all orthopedic surgeries in our department to less than 2%, Presence of fixed, known and effective prophylactic antibiotic protocol in our hospital unlike before every surgeon has his opinion about type and dose of antibiotics causing less controversy and confusion among surgeons in the practice of postoperative antibiotic use. Conclusion This study postulated that systemic antibiotic prophylaxis delivered preoperatively in intramedullary nailing of femur and tibia procedures significantly reduces the incidence of infection.

No difference in risk of revision due to infection between clindamycin and cephalosporins as antibiotic prophylaxis in cemented primary total knee replacements: a report from the Norwegian Arthroplasty Register 2005-2020.

Systemic antibiotic prophylaxis with clindamycin, which is often used in penicillin- or cephalosporin-allergic patients', has been associated with a higher risk of surgical revision for deep prosthetic joint infection (PJI) than cloxacillin in primary total knee replacement (TKR). We aimed to investigate whether clindamycin increases the risk of surgical revisions due to PJI compared with cephalosporins in primary cemented TKR. Data from 59,081 TKRs in the Norwegian Arthroplasty Register (NAR) 2005-2020 was included. 2,655 (5%) received clindamycin and 56,426 (95%) received cephalosporins. Cox regression analyses were performed with adjustment for sex, age groups, diagnosis, and ASA score. Survival times were calculated using Kaplan-Meier estimates and compared using Cox regression with revision for PJI as endpoint. The cephalosporins cefalotin and cefazolin were also compared. Of the TKRs included, 1.3% (n = 743) were revised for PJI. 96% (n = 713) had received cephalosporins and 4% (n = 30) clindamycin for perioperative prophylaxis. Comparing cephalosporins (reference) and clindamycin, at 3-month follow-up the adjusted hazard ratio rate (HRR) for PJI was 0.7 (95% confidence interval [CI] 0.4-1.4), at 1 year 0.9 (CI 0.6-1.5), and at 5 years 0.9 (CI 0.6-1.4). Analysis using propensity score matching showed similar results. Furthermore, comparing cefalotin (reference) and cefazolin, HRR was 1.0 (CI 0.8-1.4) at 3 months and 1.0 (CI 0.7-1.3) at 1-year follow-up. We found no difference in risk of revision for PJI when using clindamycin compared with cephalosporins in primary cemented TKRs. It appears safe to continue the use of clindamycin in penicillin- or cephalosporin-allergic patients.

What is the current evidence for antibiotic prophylaxis in orthopaedic surgery?

Surgical site infections (SSI) continue to represent a significant postoperative burden. SSI is associated with an increased risk of morbidity and mortality. Systemic antibiotic prophylaxis (SAP) is used to reduce the risk of SSI. Several factors must be considered for appropriate antibiotic use: antibiotic selection, timing, and duration. The evidence and use of antibiotics differs between closed fractures, open fractures, arthroplasty and percutaneous fixation. The use of SAP is a balance between reducing the incidence of SSI whilst maintaining proper antibiotic stewardship to limit adverse effects and the emergence of antibiotic resistance. This paper will discuss the evidence for the use of SAP in orthopaedic surgery and the potential adverse effects of the injudicious use of antibiotics.

EFdA efficiently suppresses HIV replication in the male genital tract and prevents penile HIV acquisition.

Sexually transmitted HIV infections in heterosexual men are acquired through the penis. Low adherence to condom usage and the fact that 40% of circumcised men are not protected indicate the need for additional prevention strategies. Here, we describe a new approach to evaluate the prevention of penile HIV transmission. We demonstrated that the entire male genital tract (MGT) of bone marrow/liver/thymus (BLT) humanized mice is repopulated with human T and myeloid cells. The majority of the human T cells in the MGT express CD4 and CCR5. Direct penile exposure to HIV leads to systemic infection including all tissues of the MGT. HIV replication throughout the MGT was reduced 100-1,000-fold by treatment with 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA), resulting in the restoration of CD4+ T cell levels. Importantly, systemic preexposure prophylaxis with EFdA effectively protects from penile HIV acquisition. IMPORTANCE Over 84.2 million people have been infected by the human immunodeficiency virus type 1 (HIV-1) during the past 40 years, most through sexual transmission. Men comprise approximately half of the HIV-infected population worldwide. Sexually transmitted HIV infections in exclusively heterosexual men are acquired through the penis. However, direct evaluation of HIV infection throughout the human male genital tract (MGT) is not possible. Here, we developed a new in vivo model that permits, for the first time, the detail analysis of HIV infection. Using BLT humanized mice, we showed that productive HIV infection occurs throughout the entire MGT and induces a dramatic reduction in human CD4 T cells compromising immune responses in this organ. Antiretroviral treatment with novel drug EFdA suppresses HIV replication in all tissues of the MGT, restores normal levels of CD4 T cells and is highly efficient at preventing penile transmission.