Systemic Broad-spectrum Antibiotics Research Articles

Formulation of three tailed bacteriophages by spray-drying and atomic layer deposition for thermal stability and controlled release

Deep infection is the second most common complication of arthroplasty following loosening of the implant. Antibiotic-loaded bone cements (ALBCs) and high concentrations of systemic broad-spectrum antibiotics are commonly used to prevent infections following injury and surgery. However, clinical data fails to show that ALBCs are effective against deep infection, and negative side effects can result following prolonged administration of antibiotics. Additionally, the rise of multidrug resistant (MDR) bacteria provides an urgent need for alternatives to broad-spectrum antibiotics. Phage therapy, or the use of bacteriophages (viruses that infect bacteria) to target pathogenic bacteria, might offer a safe alternative to combat MDR bacteria. Application of phage therapy in the setting of deep infections requires formulation strategies that would stabilize bacteriophage against chemical and thermal stress during bone-cement polymerization, that maintain bacteriophage activity for weeks or months at physiological temperatures, and that allow for sustained release of phage to combat slow-growing, persistent bacteria. Here, we demonstrate the formulation of three phages that target diverse bacterial pathogens, which includes spray-drying of the particles for enhanced thermal stability at 37 °C and above. Additionally, we use atomic layer deposition (ALD) to coat spray-dried powders with alumina to allow for delayed release of phage from the dry formulations, and potentially protect phage against chemical damage during bone cement polymerization. Together, these findings present a strategy to formulate phages that possess thermal stability and sustained release properties for use in deep infections.

Probiotics and Antibiotic-Induced Microbial Aberrations in Children

Probiotics are often considered in children to prevent antibiotic-associated diarrhea. However, the underlying mechanistic effects and impact of probiotics on antibiotic-induced microbiota changes are not well understood. To investigate the effects of a multispecies probiotic on the gut microbiota composition in children receiving antibiotics. This is a secondary analysis of a randomized, quadruple-blind, placebo-controlled clinical trial from February 1, 2018, to May 31, 2021, including 350 children receiving broad-spectrum antibiotics in the inpatient and outpatient settings. Patients were followed up until 1 month after the intervention period. Fecal samples and data were analyzed between September 1, 2022, and February 28, 2023. Eligibility criteria included 3 months to 18 years of age and recruitment within 24 hours following initiation of broad-spectrum systemic antibiotics. In total, 646 eligible patients were approached and 350 participated in the trial. Participants were randomly assigned to receive daily placebo or a multispecies probiotic formulation consisting of 8 strains from 5 different genera during antibiotic treatment and for 7 days afterward. Fecal stool samples were collected at 4 predefined times: (1) inclusion, (2) last day of antibiotic use, (3) last day of the study intervention, and (4) 1 month after intervention. Microbiota analysis was performed by 16S ribosomal RNA gene sequencing. A total of 350 children were randomized and collected stool samples from 88 were eligible for the microbiota analysis (54 boys and 34 girls; mean [SD] age, 47.09 [55.64] months). Alpha diversity did not significantly differ between groups at the first 3 times. Shannon diversity (mean [SD], 3.56 [0.75] vs 3.09 [1.00]; P = .02) and inverse Simpson diversity (mean [SD], 3.75 [95% CI, 1.66-5.82] vs -1.31 [95% CI, -3.17 to 0.53]; P = 1 × 10-4) indices were higher in the placebo group compared with the probiotic group 1 month after intervention. Beta diversity was not significantly different at any of the times. Three of 5 supplemented genera had higher relative abundance during probiotic supplementation, but this difference had disappeared after 1 month. The studied probiotic mixture had minor and transient effects on the microbiota composition during and after antibiotic treatment. Further research is needed to understand their working mechanisms in manipulating the microbiome and preventing antibiotic-associated dysbiosis and adverse effects such as antibiotic-associated diarrhea. ClinicalTrials.gov Identifier: NCT03334604.

Restrictive Versus Permissive Use of Broad-spectrum Antibiotics in Patients Receiving Allogeneic Stem Cell Transplantation and With Early Fever Due to Cytokine Release Syndrome: Evidence for Beneficial Microbiota Protection Without Increase in Infectious Complications.

Intestinal microbiome contributes to the pathophysiology of acute gastrointestinal (GI) graft-versus-host disease (GvHD) and loss of microbiome diversity influences the outcome of patients after allogeneic stem cell transplantation (SCT). Systemic broad-spectrum antibiotics have been identified as a major cause of early intestinal dysbiosis. In 2017, our transplant unit at the university hospital in Regensburg changed the antibiotic strategy from a permissive way with initiation of antibiotics in all patients with neutropenic fever independent of the underlying cause and risk to a restrictive use in cases with high likelihood of cytokine release syndrome (eg, after anti-thymocyte globulin [ATG] therapy). We analyzed clinical data and microbiome parameters obtained 7 days after allogeneic SCT from 188 patients with ATG therapy transplanted in 2015/2016 (permissive cohort, n = 101) and 2918/2019 (restrictive cohort, n = 87). Restrictive antibiotic treatment postponed the beginning of antibiotic administration from 1.4 ± 7.6 days prior to 1.7 ± 5.5 days after SCT (P = .01) and significantly reduced the duration of antibiotic administration by 5.8 days (P < .001) without increase in infectious complications. Furthermore, we observed beneficial effects of the restrictive strategy compared with the permissive way on microbiome diversity (urinary 3-indoxylsulfate, P = .01; Shannon and Simpson indices, P < .001) and species abundance 7 days post-transplant as well as a positive trend toward a reduced incidence of severe GI GvHD (P = .1). Our data indicate that microbiota protection can be achieved by a more careful selection of neutropenic patients qualifying for antibiotic treatment during allogeneic SCT without increased risk of infectious complications.

Commentary: Scleral penetration or perforation during strabismus surgery.

Commentary: Scleral penetration or perforation during strabismus surgery.

Fournier gangrene - would you KISS it?

Fournier gangrene is a disease characterized by necrotizing fasciitis of the perineal and genital region, resulting from synergistic polymicrobiotic infection. Most infections can be localized to a cutaneous, urethral, or rectal source and can culminate in a fulminant sepsis. Current state of the art is systemic broad-spectrum antibiotics and serial aggressive debridement which result in superficial perineal defect of wide dimensions. We compiled all the cases of Fournier gangrene that required reconstruction after debridement in Centro Hospitalar Universitário Lisboa Central from 2018 to 2022. Inclusion criteria were reconstruction for Fournier defects and patients' age 18 to 90 years old. Exclusion criteria were patients who didn't require reconstruction or didn't complete it due to death or transfer to another healthcare institution. Reconstructive procedures and complication rates are reported as whole numbers and percentages of total. The initial search yielded 32 patients. There were 2 (6.2%) patients with defects that healed by secondary intention, 6 (18.7%) with delayed primary closure, 4 (12.5%) with implantation of the testicle in a medial thigh pocket, 12 (37.5%) with skin grafts, 4 (12.5%) with scrotal advancement flaps, 2 (6.2%) with flaps, and 2 (6.2%) with flaps and skin grafts in combination. Four outcomes were evaluated: number of patients, defect size, method of reconstruction, and wound-healing complications. Most reconstructive techniques provide reliable coverage and protection of testicular function with an acceptable cosmetic result. The reconstructive options need to be patient tailored in order to achieve long lasting results with a minimum of postoperative morbidity.

Are Intravesical Aminoglycosides the New Gold Standard in the Management of Refractory Urinary Tract Infection: A Systematic Review of Literature.

Background: Antibiotic resistance in urinary pathogens is increasingly common, leading to rising cases of complicated urinary tract infections. Conventional antimicrobial treatment may be insufficient in these cases and broad-spectrum systemic antibiotics contribute to the problem. Intravesical aminoglycoside instillation is an alternative treatment option that delivers localized and high-dose treatment to the source of infection. This study summarizes the existing evidence for the efficacy and safety of this treatment. Methods: A systematic search was conducted of worldwide literature according to PRISMA methodology and Cochrane standards for systematic review. Studies were included if they reported outcome data for the prevention and reduction in urinary tract infections, eradication of antimicrobial-resistant organisms, or change in sensitivities allowing conventional oral antimicrobial treatment after the administration of intravesical aminoglycoside with or without polymyxin therapy. Results: The search identified 826 articles, of which, 19 were included in the final data analysis and narrative synthesis. A successful outcome was identified in 80.7% (n = 289) of patients treated with aminoglycoside alone and 79.5% (n = 163) treated with an aminoglycoside in combination with polymyxin. Discontinuation was noted in 6.2% of patients. An increase in antimicrobial sensitivity was seen in 15.3% (n = 55) and 16.3% (n = 36) in the aminoglycoside and aminoglycoside/polymyxin groups, respectively. Conclusions: Current evidence supports the use of intravesical aminoglycoside instillation as an efficacious and safe treatment for refractory UTIs. Nevertheless, data is limited, and larger volume studies with longer follow-up periods are required.

Clinical Characteristics and Outcome of Bleb-Related Infection in Glaucoma Patients

Objective: To study the clinical characteristics, causative organism, treatment, and clinical outcomes of bleb-related infection.Materials and Methods: The medical charts of patients who were diagnosed with bleb-related infection, including blebitis and bleb-related endophthalmitis (BRE), from September 2001 to December 2019 at Siriraj Hospital were reviewed. The patients’ demographic data, clinical characteristics, microorganisms found, treatment, and clinical outcomes were explored.Results: We found a total of 42 eyes from 41 patients had been diagnosed with blebitis (11 eyes) and BRE (31 eyes) over the 18-year study period. More than 80% of the patients had experienced pain and redness as the presenting symptoms. The most common bleb characteristic in BRE was purulent bleb (74.2%), while in blebitis it was bleb injection (45.5%). Bleb leakage was documented in 27.3% and 22.6% of patients with blebitis and BRE, respectively. Among the 41 patients, 10 had a history of minor trauma before the onset of infection, such as a rubbed eye, foreign body entering into the eye, water splashed into the eyes, or the eyes had been washed with soap. The yield of vitreous culture in bleb-related endophthalmitis was 48.3%. The most common microorganisms were Streptococcus spp., Enterococcus spp., and Haemophilus Influenzae. Generally, the treatment for blebitis at our institute is broad spectrum topical and systemic antibiotics, while intravitreal broad spectrum antibiotics are added to the treatment regimen for BRE patients. For BRE in our cohort, 11 eyes required vitrectomy and 7 eyes had undergone bleb excision. Treatment for blebitis tended to have a good visual outcome, with a stable visual prognosis for 9 out of the 11 eyes diagnosed with blebitis. However, most of the BRE eyes had a worsened visual outcome. Enterococcus spp. and Haemophilus Influenzae resulted in poor visual outcomes.Conclusion: The clinical characteristics of bleb-related infection in our patients were pain and redness. One fourth of patients had a history of minor trauma to the eye. To prevent bleb-related infection, the importance of patient education after trabeculectomy should be highlighted. Patients with presenting symptoms and unwanted behavior that could result in bleb infection should be identified and receive treatment alongside education.

Multispecies Probiotic for the Prevention of Antibiotic-Associated Diarrhea in Children

The efficacy of multispecies probiotic formulations in the prevention of antibiotic-associated diarrhea (AAD) remains unclear. To assess the effect of a multispecies probiotic on the risk of AAD in children. This randomized, quadruple-blind, placebo-controlled trial was conducted from February 2018 to May 2021 in a multicenter, mixed setting (inpatients and outpatients). Patients were followed up throughout the intervention period. Eligibility criteria included age 3 months to 18 years, recruitment within 24 hours following initiation of broad-spectrum systemic antibiotics, and signed informed consent. In total, 646 eligible patients were approached and 350 patients took part in the trial. A multispecies probiotic consisting of Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Lactobacillus acidophilus W37, L acidophilus W55, Lacticaseibacillus paracasei W20, Lactiplantibacillus plantarum W62, Lacticaseibacillus rhamnosus W71, and Ligilactobacillus salivarius W24, for a total dose of 10 billion colony-forming units daily, for the duration of antibiotic treatment and for 7 days after. The primary outcome was AAD, defined as 3 or more loose or watery stools per day in a 24-hour period, caused either by Clostridioides difficile or of otherwise unexplained etiology, after testing for common diarrheal pathogens. The secondary outcomes included diarrhea regardless of the etiology, diarrhea duration, and predefined diarrhea complications. A total of 350 children (192 boys and 158 girls; mean [range] age, 50 [3-212] months) were randomized and 313 were included in the intention-to-treat analysis. Compared with placebo (n = 155), the probiotic (n = 158) had no effect on risk of AAD (relative risk [RR], 0.81; 95% CI, 0.49-1.33). However, children in the probiotic group had a lower risk of diarrhea regardless of the etiology (RR, 0.65; 95% CI, 0.44-0.94). No differences were observed between the groups for most of the secondary outcomes, including adverse events. A multispecies probiotic did not reduce the risk of AAD in children when analyzed according to the most stringent definition. However, it reduced the overall risk of diarrhea during and for 7 days after antibiotic treatment. Our study also shows that the AAD definition has a significant effect on clinical trial results and their interpretation. ClinicalTrials.gov Identifier: NCT03334604.

Management of nasal myiasis and type 2 diabetes mellitus: A rare case and review article.

BackgroundNasal myiasis is a nasal infestation caused by house fly larvae (maggot). It's a rare condition with only a few reported cases and no treatment consensus.Case presentationA 54-year-old woman was admitted to the emergency unit with a complaint of larvae found in the left nasal cavity and bloody nasal discharge for 2 days. Anterior rhinoscopy found some living larvae in a narrowed left nasal cavity. Patient's management included larvae removal manually with forceps, nasal saline irrigation, a systemic broad-spectrum antibiotic, and insulin to controlled blood sugar.DiscussionRemoval of larvae in the nasal cavity using irrigation saline and systemic broad-spectrum antibiotics is effective in the absence of bone destruction.Conclusionmanual extraction combined with nasal saline irrigation and systemic broad-spectrum antibiotic was effective to manage nasal myiasis.

Necrotizing fasciitis of the upper extremity: a retrospective analysis of 19 cases

Necrotizing fasciitis (NF) is both a limb—and life—threatening disease that affects skin, hypodermis as well as superficial fascia and deep fascia by rapidly progressive necrosis. Although this serious infection frequently occurs in the extremities, upper limb NF is a rare clinical presentation. The present study attempted to evaluate the clinical profiles, paraclinical findings, treatment modalities, outcomes and predictors of morbidity and mortality in patients with NF of the upper extremity. The validity of the Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) scoring system was also assessed. Nineteen patients who were treated between January 2010 and December 2019 for NF of the upper extremity were eligible for this study. Data including demographics, clinical signs, paraclinical findings, treatment and outcomes were collected retrospectively from our medical records. Fisher's exact test was used to analyze predictive factors for mortality and morbidity. The mean age was 62 years, with a male predominance. The most common comorbidity was diabetes mellitus (42%). Main clinical manifestations were pain (79%), tense edema (79%) and a large infiltrated swollen erythematous plaque (58%). Severe sepsis and septic shock were identified in 32% and 21% of patients, respectively. Thirteen of our 19 patients (68%) were identified as having a high or intermediate likelihood of NF based of the LRINEC scoring system, while the other 6 (32%) were classified as having low likelihood. All patients received systemic broad spectrum antibiotic therapy in addition to surgical debridement. Two patients (10%) died and one (5%) required amputation. Mortality was associated with septic shock (p = 0.006), delay in surgery >24 h (p = 0.018), creatininemia >141 mmol/l (p = 0.018) and LRINEC score ≥ 8 (p = 0.035). Otherwise, anemia (p = 0.021), hypercreatininemia (p = 0.001) and delayed surgical debridement (p = 0.001) were risk factors for morbidity and mortality. The surviving patients underwent reconstructive surgery (skin grafting after wound preparation by using vacuum therapy) with positive outcome. Early diagnosis coupled with emergent surgical debridement and broad-spectrum empiric antibiotic therapy are the keystones of a successful outcome. The LRINEC score was not strongly correlated to the true diagnosis of NF and was a prognostic tool rather than a diagnostic one.

Sight-threatening intraocular infection in patients with COVID-19 in India.

Purpose:Intraocular infection in patients with COVID-19 could be different in the presence of treatment with systemic corticosteroid and immunosuppressive agents. We describe the epidemiology and microbiological profile of intraocular infection in COVID-19 patients after their release from the hospital.Methods:We analyzed the clinical and microbiological data of laboratory-confirmed COVID-19 patients from April 2020 to January 2021 presenting with features of endogenous endophthalmitis within 12 weeks of their discharge from the hospital in two neighboring states in South India. The data included demography, systemic comorbidities, COVID-19 treatment details, time interval to visual symptoms, the microbiology of systemic and ocular findings, ophthalmic management, and outcomes.Results:The mean age of 24 patients (33 eyes) was 53.6 ± 13.5 (range: 5–72) years; 17 (70.83%) patients were male. Twenty-two (91.6%) patients had systemic comorbidities, and the median period of hospitalization for COVID-19 treatment was 14.5 ± 0.7 (range: 7–63) days. Infection was bilateral in nine patients. COVID-19 treatment included broad-spectrum systemic antibiotics (all), antiviral drugs (22, 91.66% of patients), systemic corticosteroid (21, 87.5% of patients), supplemental oxygen (18, 75% of patients), low molecular weight heparin (17, 70.8% of patients), admission in intensive care units (16, 66.6% of patients), and interleukin-6 inhibitor (tocilizumab) (14, 58.3% of patients). Five (20.8%) patients died of COVID-19-related complications during treatment for endophthalmitis; one eye progressed to pan ophthalmitis and orbital cellulitis; eight eyes regained vision >20/400. Fourteen of 19 (73.7%) vitreous biopsies were microbiologically positive (culture, PCR, and microscopy), and the majority (11 patients, 78.5%) were fungi.Conclusion:Intraocular infection in COVID-19 patients is predominantly caused by fungi. We suggest a routine eye examination be included as a standard of care of COVID-19.

Our Experience on The Use of Dimexid (Dimethyl Sulfoxide) in The Effective management of Lung abscess

A lung abscess is a localized area of pulmonar parenchymal necrosis caused by an infectious anism Primar lung abscesses occur in immunocompromised patients. Secondary lung abscesses occur in patients with an underlying pulmonary disease. Systemic broad spectrum antibiotics, pulmonary physiotherapy, postural drainage and interventional or surgical drainage and surgical pulmonary resection in selected cases, are main modalities in the management of lung abscesses. A distressing fact is the long course of recovery and complications encountered in the management of lung abscesses. Severe complications like massive haemoptysis, endobronchial spread, rupture into the pleural space, pyopneumothorax, empyema, broncho pleural fistula, septic shock and respiratory failure have been reduced with advances in treatment, as mentioned above. Dimexid Dimethyl Sulfoxide possesses strong anti inflammatory, analgesic, antioxidant and antimicrobial actions it changes the sensitivity of microflora resistant to antibiotics.

Select health care–associated infections are declining

Central line–associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), and Clostridioides difficile infections all declined between 2017 and 2018 across four health care settings, according to CDC’s National and State Healthcare-Associated Infections Progress Report, released in November 2019. Health care–associated infections can result in increased morbidity and mortality, length of hospital stay, and health care–associated costs. The report compiles data from more than 22,000 active hospitals and other health care facilities: acute care hospitals, critical access hospitals, inpatient rehabilitation facilities, and long-term acute care hospitals. The results suggest that interventions targeted at reducing these types of infections appear to be working, with antibiotic stewardship efforts a main factor in the declining rates. Overall, CLABSIs decreased 9% between 2017 and 2018, with the largest decrease in the ICU (11%). One intervention that has led to reduced CLABSI rates is bundle implementation with use of chlorhexidine dressings, said Amy Hanson, PharmD, BCPS AQ-ID, an antimicrobial stewardship and infectious disease pharmacist at the Chicago Department of Public Health, in an interview with Pharmacy Today. “In a study conducted during my time at Rush [University Medical Center in Chicago], we published data showing that moving from peripheral draw to phlebotomist draw via central lines had a reduction in CLABSI rates over time, by reducing the contamination risk (false-positive CLABSIs),” said Hanson. “This was particularly true in certain patient populations, such as our hematology/oncology patients. We were also able to show a reduction in vancomycin use over time.” For CAUTIs, there was about an 8% decrease between 2017 and 2018, with the largest decrease also observed in the ICU for this infection (10%). Hanson noted that a number of basic interventions could have contributed to the reduction in CAUTI rates, such as the many interventions focused primarily on education and training. Others include local adoption of guidelines or protocols, use of an opinion leader, audit and feedback, multidisciplinary team involvement, and reminders and stop orders. Hospital-onset C. difficile infections saw about a 12% decrease between 2017 and 2018. Antibiotic stewardship intervention efforts aimed at lowering C. difficile rates, such as those recommended in the C. difficile guidelines of the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America, have surely contributed to this decline, noted Hanson. These include implementation of restrictions on the use of certain antibiotics (primarily fluoroquinolones) and the potentially broader use of prophylactic oral vancomycin in high-risk patients receiving broad-spectrum systemic antibiotics. Another CDC report, Antibiotic Resistance Threats in the U.S. 2019, revealed improvements in select areas, with 18% fewer deaths from antibiotic resistance and 28% fewer deaths from antibiotic resistance in hospitals. When individual pathogens were assessed, infections caused by vancomycin-resistant Enterococcus decreased by 41%, multidrug-resistant Pseudomonas aeruginosa by 29%, methicillin-resistant Staphylococcus aureus (MRSA) by 21%, carbapenem-resistant Acinetobacter baumannii by 33%, and drug-resistant Candida species by 25%. Rates of carbapenem-resistant Enterobacteriaceae and drug-resistant tuberculosis disease cases remained stable. CDC attributed some of these findings to interventions that focus on preventing device- and procedure-related infections, such as urinary catheters or central lines; stopping the spread of resistant germs within and between health care facilities; containing emerging threats through early detection and aggressive response; tracking and improving appropriate antibiotic use; and infection prevention and control in nonhospital settings, such as long-term-care facilities. Although rates of CLABIs, CAUTIs, and C. difficile appear to be declining, other infections saw no change in their rates between 2017 and 2018, including ventilator-associated pneumonia, skin and soft tissue infections, and hospital-onset MRSA bacteremia. In addition, in CDC’s report on antibiotic resistance, the agency reported that more than 2.8 million antibiotic-resistant infections—and more than 35,000 deaths from antibiotic resistance—occur each year. These data suggest that more work needs to be done to help reduce the rates of these infections. Pharmacists working in acute and long-term health care settings can play an active role in helping implement interventions aimed at improving the rates of these infections, with a focus on antibiotic stewardship efforts.

Association of Adverse Drug Events with Broad-spectrum Antibiotic Use in Hospitalized Patients: A Single-center Study.

Objective The importance of antimicrobial stewardship is increasingly highlighted in this age of antimicrobial resistance. A better comprehension of adverse drug events (ADEs) can promote the appropriate use of antibiotics. We aimed to quantify the incidence of ADEs associated with broad-spectrum systemic antibiotics in a hospital setting. Methods We conducted a six-month prospective, observational study at Osaka University Hospital to describe the incidence of ADEs in patients hospitalized in general wards undergoing treatment with broad-spectrum antibiotics [carbapenems, piperacillin/tazobactam (PIPC/TAZ), and anti-methicillin-resistant Staphylococcus aureus agents]. The occurrence of ADE was defined as any cardiac, gastrointestinal, hepatobiliary, renal, neurologic, hematologic, dermatologic, or musculoskeletal manifestation after 48 hours or more of systemic antibiotic therapy. Results The 3 most frequently prescribed antibiotics were PIPC/TAZ (242 cases), meropenem (181 cases), and vancomycin (92 cases). Of 689 patients, 118 (17.1%) experienced ADEs, including gastrointestinal (6.4%), hepatobiliary (4.2%), dermatologic (2.5%), and renal (2.3%) manifestations. Patients treated with PIPC/TAZ, meropenem, doripenem, vancomycin, daptomycin, and teicoplanin developed ADEs at rates of 20.7%, 16.0%, 15.4%, 19.6%, 11.8%, and 10.9%, respectively. Conclusion Our study provides a quantitative value for the incidence of ADEs associated with broad-spectrum antibiotics in clinical practice. To optimize patient safety, clinicians need to be aware of the risks associated with antibiotic administration.

Surgical Treatment of Paediatric Chronic Rhinosinusitis.

Rhinosinusitis (RS) is a common disease in children, significantly affecting their quality of life. Chronic rhinosinusitis (CRS) is frequently linked to other respiratory diseases, including asthma. Children affected by CRS may be candidates for surgery in the case of failure of maximal medical therapy comprising three to six weeks of broad-spectrum systemic antibiotics with adjunctive therapies. Although endoscopic sinus surgery (ESS) is the surgical treatment of choice in adult patients with CRS, different surgical procedures are scheduled for refractory paediatric CRS and include adenoidectomy, paediatric ESS (PESS), and balloon catheter sinuplasty (BCS). The present paper discusses the indications and limitations of each treatment option in children with CRS. Given the amount of current evidence, it is reasonable to suggest that, in young and otherwise healthy children with refractory CRS, an adenoidectomy (eventually combined with BCS) should be offered as the first-line surgical treatment. Nevertheless, this approach may be considered ineffective in some patients who should be candidates for traditional ESS. In older children, those with asthma, or in the case of peculiar conditions, traditional ESS should be considered as the primary treatment.

Peptic ulcer disease: a critical analysis of the current state of the problem

History of study of peptic ulcer, evolution of ideas about its etiology and pathogenesis are set out in this review. The precedingtheories of the formation of peptic ulcer and the current provisions explaining the development of this disease are described. Special attention is paid to the role of the bacterium Helicobacter pylori put forwardin the occurrence of peptic ulcer and the formation of its recurrence; the microbiological and genetic features of helicobacteria are described in detail, giving them unique pathogenic properties. The genetic, immune, psychogenic mechanisms of the pathogenesis of peptic ulcer are described, the significance of oxidative stress and local factors in the formation of the ulcerative defect of the mucous membrane is revealed. A thorough critical analysis of some of the provisions of the dominant theory of ulcerogenesisis carried out. The inconsistency of helicobacteria, which are considered the main etiological factor of peptic ulcer, to the requirements of the Koch Triad, is emphasized: this pathogen does not always provoke the development of erosive-ulcerative mucosal lesions and is frequently not detected in many patients with peptic ulcer. Own data illustrating the dysbiotic nature of the violation of the microbial landscape of the stomach, and not the prevalence of helicobacteria in patients with peptic ulcer, are presented. Clinical features of peptic ulcer disease are properly described. Statements of the Maastricht consensus are strongly criticized for contradicting the basic principles of evidence-based medicine and not allowing the use of clinical thinking, analysis and synthesis of evidence. There is a doubt about the feasibility of the eradication of helicobacteria using the systemic broad-spectrum antibiotics. The rationale for further comprehensive study of peptic ulcer and the development of new, more effective therapeutic agents is put forward.

Use of regional limb perfusion with amikacin sulphate in the treatment of a severe soft tissue infection in the extremity of a dog

Intravenous regional limb perfusion (RLP) has been used extensively in equine and human practice to deliver high doses of antimicrobials to bones, joints and the soft tissues in the distal...

Pyoderma gangrenosum: a presenting sign of myelodysplastic syndrome in undiagnosed Fanconi anemia

A 26-year-old man with a history of congenital bilateral microtia, unilateral renal agenesis, left aural atresia, and right external auditory canal occlusion admitted for right rib cartilage graft harvest and left ear re-construction. Following surgery, an ulceration with violaceous borders and a yellow fibrinous base unresponsive to broad-spectrum antibiotics developed at the harvest site. The wound was expanding and not responsive to systemic broad-spectrum antibiotics. Biopsy revealed a dense dermal infiltrate of neutrophils with negative tissue cultures consistent with pyoderma gangrenosum (PG). He was treated with systemic, intralesional, and topical steroids, as well as doxycycline. Three weeks after the diagnosis of PG, he was found to have persistent anemia and leukopenia. Bone marrow aspiration analysis was consistent with hypocellular myelodysplastic syndrome and genetic testing was consistent with Fanconi anemia. There is a well-known association of PG with hematological disorders. Fanconi anemia is a rare genetic hematologic disorder with congenital defects leading to bone marrow failure and malignancy in long-standing disease. In our patient, we consider his development of PG a paraneoplastic sign associated with the onset of his hypocellular myelodysplastic syndrome.

Detrimental Effect of Broad-spectrum Antibiotics on Intestinal Microbiome Diversity in Patients After Allogeneic Stem Cell Transplantation: Lack of Commensal Sparing Antibiotics.

Maintaining gastrointestinal (GI) microbiome diversity plays a key role during allogeneic stem cell transplantation (ASCT), and loss of diversity correlates with acute GI graft versus host disease (GvHD) and poor outcomes. In this retrospective analysis of 161 ASCT patients, we used serial analyses of urinary 3-indoxyl sulfate (3-IS) levels and GI microbiome parameters within the first 10 days after ASCT to identify potential commensal microbiota-sparing antibiotics. Based on antibiotic activity, we formed 3 subgroups (Rifaximin without systemic antibiotics, Rifaximin with systemic antibiotics, and Ciprofloxacin/Metronidazole with/without systemic antibiotics). Mono-antibiosis with Rifaximin revealed higher 3-IS levels (P < .001), higher Clostridium cluster XIVa (CCXIVa) abundance (P = .004), and higher Shannon indices (P = .01) compared to Ciprofloxacin/Metronidazole with/without systemic antibiotics. Rifaximin followed by systemic antibiotics maintained microbiome diversity compared to Ciprofloxacin/Metronidazole with/without systemic antibiotics, as these patients showed still higher 3-IS levels (P = .04), higher CCXIVa copy numbers (P = .01), and higher Shannon indexes (P = .01). Even for this larger cohort of patients, the outcome was superior with regard to GI GvHD (P = .05) and lower transplant-related mortality (P < .001) for patients receiving Rifaximin plus systemic antibiotics compared to other types of systemic antibiotic treatment. Antibiosis with Ciprofloxacin/Metronidazole (n = 12, P = .01), Piperacillin/Tazobactam (n = 52, P = .01), Meropenem/Vancomycin (n = 16, P = .003), Ceftazidime (n = 10, P = .03), or multiple systemic antibiotics (n = 53, P = .001) showed significantly lower 3-IS levels compared to mono-antibiosis with Rifaximin (n = 14) or intravenous Vancomycin (n = 4, not statistically significant). Different types of antibiotic treatments show different impacts on markers of microbiome diversity. The identification of antibiotics sparing commensal bacteria remains an ongoing challenge. However, Rifaximin allowed a higher intestinal microbiome diversity, even in the presence of systemic broad-spectrum antibiotics.

Savremeni pristup u terapiji infekcija izazvanih sa Clostridium difficile

Infection caused by Clostridium difficile (CDI) occurs as a result of imbalance of bacteria in intestinal tract mainly due to previous exposure to wide-spectrum systemic antibiotics. Nowadays, it is recognized as one of the most frequent infections acquired in hospitals. Contemporary clinicians often face an increased incidence of fulminant and recurrent CDIs that are accompanied with a number of colectomies, prolonged stay in hospitals, fatal outcome, and rising healthcare costs. Traditional antibiotics for CDI, such as metronidazole, vancomycin or fidaxomicin, have been linked to certain treatment limitations in previous studies. Thus, the aim of this narrative mini literature review was to critically evaluate efficiency of each of the recommended modern therapy modalities for CDI, as well as the frequency and severity of adverse events associated with their use. Based on current knowledge, the range of standard antibiotics approved for treatment of initial or recurrent CDI remains quite limited. Regardless of severity of CDI, oral or rectal vancomycin should be considered as the first-line therapeutic option in adults and children, while fidaxomicin or metronidazole could be an appropriate alternative. The other potentially effective antimicrobials against CDI, such as rifaximin, nitazoxanide, fusidic acid, tigecyclin, bacitracin and use of probiotics cannot be advised as the therapy of choice, as they did not provide any advantage over vancomycin or fidaxomicin in prior investigations. In an attempt to solve the problem of recurrent CDI events, which is one of the most important challenges facing health professionals today, adjunct use of human monoclonal antibody against toxin B (bezlotoxumab) or instillation of normal colonic bacteria obtained from healthy donor into patient's intestine (Fecal Microbiota Transplantation), could be effective and safe approach where available. Besides clinical development of innovative therapy for CDI, such as new antibiotics and vaccines, primary focus should be on effective prevention of this infection, in terms of improving rational use of broad-spectrum systemic antibiotics and proton pump inhibitors.