Concomitant Antibiotic Therapy Research Articles

Improving Clostridioides difficile Infectious Disease Treatment Response via Adherence to Clinical Practice Guidelines.

Clostridioides difficile (C. difficile) is a predominant nosocomial infection, and guidelines for improving diagnosis and treatment were published in 2017. We conducted a single-center, retrospective 10-year cohort study of patients with primary C. difficile infectious disease (CDID) at the largest referral Lithuanian university hospital, aiming to evaluate the clinical and laboratory characteristics of CDID and their association with the outcomes, as well as implication of concordance with current Clinical Practice Guidelines. The study enrolled a total of 370 patients. Cases with non-concordant CDID treatment resulted in more CDID-related Intensive Care Unit (ICU) admissions (7.5 vs. 1.8%) and higher CDID-related mortality (13.0 vs. 1.8%) as well as 30-day all-cause mortality (61.0 vs. 36.1%) and a lower 30-day survival compared with CDID cases with concordant treatment (p < 0.05). Among cases defined by two criteria for severe CDID, only patients with non-concordant metronidazole treatment had refractory CDID (68.8 vs. 0.0%) compared with concordant vancomycin treatment. In the presence of non-concordant metronidazole treatment for severe CDID, only cases defined by two severity criteria had more CDID-related ICU admissions (18.8 vs. 0.0%) and higher CDID-related mortality (25.0 vs. 2.0%, p < 0.05) compared with cases defined by one criterion. Severe comorbidities and the continuation of concomitant antibiotics administered at CDID onset reduced (p < 0.05) the 30-day survival and increased (p = 0.053) 30-day all-cause mortality, with 57.6 vs. 10.7% and 52.0 vs. 25.0%, respectively. Conclusions: CDID treatment non-concordant with the guidelines was associated with various adverse outcomes. In CDID with leukocytes ≥ 15 × 109/L and serum creatinine level > 133 µmol/L (>1.5 mg/dL), enteral vancomycin should be used to avoid refractory response, as metronidazole use was associated with CDID-related ICU admission and CDID-related mortality. Severe comorbidities worsened the outcomes as they were associated with reduced 30-day survival. The continuation of concomitant antibiotic therapy increased 30-day all-cause mortality; thus, it needs to be reasonably justified, deescalated or stopped.

Are corticosteroids safe in adolescent and adult patients with infectious mononucleosis? A retrospective cohort study

Background and aimThe use of systemic corticosteroids during Epstein-Barr virus (EBV)-induced infectious mononucleosis is a controversial but widespread practice. We aimed to investigate the frequency of complications in adolescents and adults with infectious mononucleosis in relation to the use of corticosteroids. MethodsWe reviewed the clinical records of 396 patients admitted to the hospital with infectious mononucleosis (52.0% male; median age, 19 years; range, 15–87 years), with a focus on both short-term (infectious and non-infectious) and long-term (hematological malignancies) complications in relation to corticosteroid use. ResultsA total of 155 (38.6%) patients received corticosteroids at some point during infectious mononucleosis. Corticosteroid use was significantly (P≤0.002) associated with sore throat, lymphadenopathy, leukocytosis, and with antibiotics use (mainly indicated after suspicion of tonsillar bacterial superinfection). Overall, 139/155 (89.7%) patients who were treated with corticosteroids also received antibiotics either before or during hospitalization, compared with 168/241 (69.7%) patients who did not. The frequency of short-term severe complications, either infectious (peritonsillar–parapharyngeal abscess or bacteremia) or non-infectious (splenic rupture, severe thrombocytopenia, myopericarditis, or lymphocytic meningitis) were similar in patients receiving and not receiving corticosteroids. After a median of 15 years of follow-up, only one Hodgkin's lymphoma was diagnosed, in a patient who was not treated with corticosteroids during infectious mononucleosis. ConclusionsThe use of systemic corticosteroids during EBV-induced infectious mononucleosis is generally safe, at least with concomitant antibiotic therapy. However, this should not encourage the use of corticosteroids in this context, given that their efficacy has yet to be demonstrated.

Warfarin and Antibiotics: Drug Interactions and Clinical Considerations.

Warfarin administration poses a notable challenge in clinical practice due to the increased susceptibility of patients to major bleeding, particularly when co-administered with other medications capable of modulating its metabolic pathways. Among these medications, antibiotics have been recognized as potential agents that can either induce or inhibit cytochrome P450-2C9, thereby impacting the effects of warfarin. A wealth of evidence from numerous studies consistently supports an elevated risk of serious bleeding in patients concurrently receiving antibiotics and warfarin therapy. This narrative review elucidates the intricate interactions between warfarin and various antibiotic classes. Notably, significant increases in the International Normalized Ratio (INR) were observed among warfarin-treated patients receiving penicillin derivatives, fluoroquinolones, TMP-SMX, and macrolides. Conversely, investigations have also demonstrated a reduction in INR levels in patients on warfarin when exposed to rifampin, a potent inducer of cytochrome P-450. Intriguingly, cephalosporin antibiotics and amoxicillin/clavulanate, despite not interfering with the cytochrome P450 system, exhibited a positive association with increased INR values. The findings of this narrative review underscore the importance of diligent monitoring in patients on warfarin requiring concomitant antibiotic therapy, as this surveillance strategy proves pivotal in mitigating the risk of major bleeding complications. Additionally, for patients necessitating cytochrome P450 inhibitors such as penicillin derivatives, fluoroquinolones, TMP-SMX, and macrolides, the consideration of dose reduction in warfarin therapy may confer substantial benefits in reducing the occurrence of major bleeding events. Similarly, patients who are co-administered rifampin alongside warfarin necessitate vigilant monitoring, with a potential need for escalating warfarin doses to counteract the risk of a hypercoagulable state.

Translated article] Analysis of results of open and percutaneous disc biopsy in the diagnosis of spondylodiscitis

IntroductionSpinal disc biopsy is a necessary tool in diagnosing and treating spondylodiscitis. Its profitability varies according to the technique, concomitant antibiotics therapy or causative germ. We studied the results of this procedure in our institution. Materials and methodsRetrospective analysis of all cases requiring disc biopsy due to possible spondylodiscitis over a 5 year period, both percutaneous (26 cases) and open (13 cases). We collected filiation and clinical data, comorbidity, concomitant antibiotic therapy, imaging tests, biopsy type, cultures results and clinical evolution. Results39 patients; 66.7% male, 66.9 years of average age. 74% has known risk factors. The main symptom was pain (89.7%). Fever occurred in 5%. MRI performed in 87%. Lumbar involvement in 76.9%. 9 patients (23%) received antibiotic treatment simultaneously with biopsy. In these cases biopsy always yielded a negative result, but positive in patients without antibiotics at the time of the biopsy (53.3%), with statistical significance. Most frequent isolated microorganisms were gram-negative bacilli (31.2%) and gram-positive cocci (31.2%). We found 2 deaths during admission for sepsis (within the first month after diagnosis). Of the rest of patients, 5 died late during the follow-up: 3 due to new infections and 2 due to subsequent complications of previous pathologies. The remaining patients with final diagnosis of spondylodiscitis evolved satisfactorily with antibiotic therapy. ConclusionsSpondylodiscitis is potentially serious and requires an adequate diagnosis, with disc biopsy being a necessary procedure on occasions. Patients poor clinical condition can make it impossible to withdraw antibiotics, which drastically reduces the performance of the biopsy.

Risk Factors for COVID-19 Associated Mucormycosis: The Ophthalmologist's Perspective.

The COVID-19 pandemic has led to a dramatic rise in the incidence of rhino-orbito-cerebral mucormycosis (ROCM) in India. The purpose of our report is to describe the prevalence of ROCM in the context of SARS-CoV-2 infection during the second Indian COVID-19 wave, as well as its diagnostics proceeding, and to discuss the challenges met in the time frame from the suspected diagnosis to the therapeutic decision in such patients. We conducted a retrospective multicentre case series study at six centres of Sudhalkar and Raghudeep group of hospitals in India. ROCM was confirmed in 38 (2.5%) of the 1546 patients admitted with SARS-CoV-2 infection. The average time to establish a diagnosis was 16 days. In total, 19 (50%) patients suffered from type 2 diabetes and were mostly treated with hypoglycaemic agents (in 90% of cases). The standard of care for SARS-CoV-2 management included systemic steroids therapy, intravenous remdesivir for 5 days, and concomitant prophylactic antibiotic therapy following admission. The median (IQR) blood glucose levels in all patients during the course of hospitalisation was 320 (250.5–375) mg/dl. A total of 16% of patients had an irreparable functional loss, and the mortality was 5%. We may hypothesise that excessive administration of antibiotics that profoundly affects human microbiota, coupled with poorly controlled glycaemia and unprotocolised haphazard steroid administration, contribute to a favourable setting for mucormycosis infections.

Re-evaluation of cefepime or piperacillin-tazobactam to decrease use of carbapenems in extended-spectrum beta-lactamase-producing Enterobacterales bloodstream infections (REDUCE-BSI).

To re-examine the use of noncarbapenems (NCBPs), specifically piperacillin-tazobactam (PTZ) and cefepime (FEP), for extended-spectrum beta-lactamase-producing Enterobacterales bloodstream infections (ESBL-E BSIs). Retrospective cohort study. Tertiary-care, academic medical center. The study included patients hospitalized between May 2016 and May 2019 with a positive blood culture for ESBL-E. Patients were excluded if they received treatment with antibiotics other than meropenem, ertapenem, PTZ, or FEP. Patients were also excluded if they were aged <18 years, received antibiotics for <24 hours, were treated for polymicrobial BSI, or received concomitant antibiotic therapy for a separate gram-negative infection. We compared CBPs with FEP or PTZ for the treatment of ESBL-E BSI. The primary outcome was in-hospital mortality. Secondary outcomes included clinical cure, microbiologic cure, infection recurrence, and resistance development. Data from 114 patients were collected and analyzed; 74 (65%) patients received carbapenem (CBP) therapy and 40 (35%) patients received a NCBP (30 received FEP and 10 received PTZ). The overall in-hospital mortality was 6% (N = 7), with a higher death rate in the CBP arm than in the N-CBP arm, (8% vs 3%; P = .42). No difference in mortality was detected between subgroups with Pitt bacteremia score ≥4, those requiring ICU admission, those whose infections were cause by a nongenitourinary source or causative organism (ie, 76 had Escherichia coli and 38 had Klebsiella spp). We detected no differences in secondary outcomes between the groups. Compared to CBPs, FEP and PTZ did not result in greater mortality or decreased clinical efficacy for the treatment of ESBL-E BSI caused by susceptible organisms.

Análisis de los resultados de la biopsia discal abierta y percutánea en el diagnóstico de la espondilodiscitis

IntroductionSpinal disc biopsy is a necessary tool in diagnosing and treating spondylodiscitis. Its profitability varies according to the technique, concomitant antibiotics therapy or causative germ. We studied the results of this procedure in our institution. Materials and methodsRetrospective analysis of all cases requiring disc biopsy due to possible spondylodiscitis over a 5year period, both percutaneous (26 cases) and open (13 cases). We collected filiation and clinical data, comorbidity, concomitant antibiotic therapy, imaging tests, biopsy type, cultures results and clinical evolution. Results39 patients; 66.7% male, 66.9years of average age. 74% has known risk factors. The main symptom was pain (89.7%). Fever occurred in 5%. MRI performed in 87%. Lumbar involvement in 76.9%. 9 patients (23%) received antibiotic treatment simultaneously with biopsy. In these cases biopsy always yielded a negative result, but positive in patients without antibiotics at the time of the biopsy (53.3%), with statistical significance. Most frequent isolated microorganisms were gram-negative bacilli (31.2%) and gram-positive cocci (31.2%). We found 2 deaths during admission for sepsis (within the first month after diagnosis). Of the rest of patients, 5 died late during the follow-up: 3 due to new infections and 2 due to subsequent complications of previous pathologies. The remaining patients with final diagnosis of spondylodiscitis evolved satisfactorily with antibiotic therapy. ConclusionsSpondylodiscitis is potentially serious and requires an adequate diagnosis, with disc biopsy being a necessary procedure on occasions. Patients poor clinical condition can make it impossible to withdraw antibiotics, which drastically reduces the performance of the biopsy.

Patient and Therapy-Related Factors Affecting the Toxicity of Pegylated-Asparaginase for the Treatment of Adult Acute Lymphoblastic Leukemia

The application of pediatric regimens in the treatment of adult acute lymphoblastic leukemia (ALL) has led to a significant improvement in patients outcome. However, concerns about the feasibility of more intensive therapies and of the use of pegylated L-Asparaginase (PEG-ASP) in adult patients have emerged. Some patient-related risk factors as high BMI or hepatic steatosis have been already identified as risk factors for the development of PEG-ASP related toxicity, but few data are available on the toxic effectof PEG-ASP when combined with other drugs.The aim of the present study was to evaluate the incidence of PEG-ASP related adverse events in a cohort of adult ALL patients in order to identify potential patient and therapy-related risk factors contributing to toxicity.Since 2013, 21 adult ALL patients received PEG-ASP therapy in our institution. Median age was 44 (range 19-76); 12 patients were treated in frontline setting (7 according to a full pediatric protocol) whereas 9 patients received therapy for relapsed/refractory leukemia. We retrospectively analyzed each single course which included PEG-ASP administration as an independent event, accounting 41episodes. Patients' features (age, BMI, disease status) and concomitant therapies were accurately analyzed as factors potentially affecting PEG-ASP toxicity. The incidence of major thrombotic/bleeding complications and grade III/IV hepatic or pancreatic toxicity was analyzed; toxicity grading and management of PEG-ASP related complications were performed according to guidelines recently published by Stock et al.No grade III/IV pancreatic, thrombotic or hemorrhagic adverse events were recorded. Five patients experienced grade III hepatic toxicity and in 3 cases grade IV toxicity was observed. All 3 patients experienced unexplained severe weight gain and painful epathomegaly, a clinical picture resembling sinusoidal occlusive disease, and ultrasonography showed the onset of acute liver steatosis. All of them had received concomitant therapy with idarubicin, vincristine and vancomycin.In univariate analysis, the incidence of grade III/IV hepatic toxicity was significantly higher when concomitant chemotherapy with at least 2 mg/sqm cumulative dose of vincristine (p 0.044, HR 4.75) or at least 16 mg/sqm cumulative dose of idarubicine (p 0.046, HR1.45) were administered. Steroids therapy determined a borderline increase in toxicity risk (p 0.068, HR 1.688). No increase in toxicity was observed with any dosing of daunorubicin, cyclophosphamide, cytarabine, methotrexate and 6-mercaptopurine. Among concomitant antibiotic therapies, vancomycin administration seemed to increase the incidence of grade III/IV hepato-toxicy (p 0.02, HR 1.863). No significant increase was observed with carbapenems and azoles (Tab I). Older age (>45), receiving PEG-ASP with active leukemia or a high BMI (>25) were not related with an increased incidence of grade III/IV hepato-toxicity (Tab I). Notably, none of the patients undergoing full pediatric induction (who received the highest doses of PEG-ASP), regardless of age (ranging from 21 to 55), experienced grade III/IV hepatotoxicity. Multivariate logistic regression analysis disclosed that concomitant administration of idarubicin, vincristine or vancomycin were independent predictors of grade III/IV hepatotoxicity (p 0.004, 0.027 and 0.042, respectively, Tab. I).Our data show that the toxicity profile of PEG-ASP in adult patients is manageable. However, serious warnings emerge from our experience. Concomitant drugs and their timing of administration may play a crucial role contributing to PEG-ASP hepatic toxicity. In order to attempt to reduce toxicity, anthracyclines with shorter half-life, i.e. daunorubicin instead of idarubicin, should be used. A particular attention should be paid when administration of concomitant antibiotic therapy is required. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Stool microbiota profiling of patients with muscle invasive bladder cancer receiving neoadjuvant pembrolizumab.

4533 Background: Immune checkpoint inhibitors (ICIs) showed efficacy in metastatic urothelial carcinoma (UC) and promising activity in muscle-invasive and non-muscle invasive UC of the bladder. Recent studies revealed the immunomodulatory effect of the gut microbiota on ICIs efficacy across several malignancies, identifying microbial “signatures” associated with response to therapy and effective antitumoral T-cell activity. In our study, we aimed to study the stool microbiota in patients undergoing neoadjuvant immunotherapy (IO) for muscle-invasive UC. Methods: Pre-IO stools were available for analysis from 42 patients enrolled in the PURE-01 trial (NCT02736266), testing 3x200mg flat-dose pembrolizumab every 21 days before radical cystectomy (RC). All samples were collected using Stool Nucleic Acid Collection and Preservation Tubes (Norgen) and extracted using the Stool DNA Isolation Kit (Norgen), according to the manufacturer’s protocol. 16s sequencing was performed using standardized protocols at the internal facility, using mock communities and DNA standards (ZymoBIOMICS) to control for extraction and sequencing contaminations. A QIIME-based bioinformatic pipeline was used for microbiome analyses. Complete response (CR) to neoadjuvant IO was defined as ypT0N0 at pathologic examination on radical cystectomy specimens, while partial response (PR) was defined as &lt; ypT2N0. Concomitant antibiotic therapy (ABT) was defined as any ATB between 30 days prior to the first pembrolizumab dose and the planned RC. Results: In our study sample, 23 patients responded to IO (21 CR + 2 PR). Overall median age was 68.5 years. Among responders, 20 (87%) patients had a smoking history (vs. 15 (79%) in non-responders) and 4 (17%) underwent concomitant ABT (vs. 6 (32%) in non-responders). Alpha-diversity assessed by richness (ACE index) was higher in responders vs. non-responders (p = 0.05), while no significant diversity was found. Beta-diversity did not show clear clustering of responders vs. non-responders. LEfSe identified 16 bacterial taxa with a linear discriminant analysis (LDA) score ≥2.5 that were differently enriched between responders and non-responders. Among them, we identified the genus Sutterella enriched in responders (p = 0.02), while the species Ruminococcus bromii was enriched in non-responders (p = 0.02). Conclusions: Our analyses showed an association between response to neoadjuvant-IO and microbiome composition in an intention-to-cure population with muscle invasive UC. We found bacterial taxa specifically enriched in responders or non-responders using pre-therapy stool specimens. The identified taxa may be tested in future studies as potential indicators of therapy outcomes, alone or in combination with other IO biomarkers. These results may also inspire new strategies of gut microbiota modulation to promote response in immunotherapy-refractory patients.

Does the alpha-defensin lateral flow test conserve its diagnostic properties in a larger population of chronic complex periprosthetic infections? Enlargement to 112 tests, from 42 tests in a preliminary study, in a reference center

BackgroundDiagnosis of periprosthetic infection (PPI) is crucial for management of bone and joint infection. The preoperative gold-standard is joint aspiration, providing results after 2-14 days’ culture, with non-negligible false negative rates due to the fragility of certain micro-organisms and/or prior antibiotic treatment. The Synovasure™ alpha-defensin lateral flow test (Zimmer, Warsaw, IN, USA) contributes within minutes to joint fluid diagnosis of almost all infectious agents, including in case of concomitant antibiotic therapy. Validity remains controversial, notably in complex microbiological situations: multi-operated patients, diagnostic doubt despite iterative sterile culture, long-course antibiotic therapy. We extended a prospective study reported in 2018, to determine whether the test maintained diagnostic value in a larger population, assessing 1) negative (NPV) and positive (PPV) predictive value, and 2) sensitivity and specificity. HypothesisSynovasure™ maintains NPV above 95% in a broader population of microbiologically complex suspected PPI. Material and methodsSynovasure™’s performance was assessed between October 2015 and October 2019 in 106 patients (112 tests) in complex diagnostic situations: 37 discordant cultures (discordant findings between 2 samples), 65 cases with clinically or biologically suspected infection but iterative sterile culture, 10 emergencies (requiring surgery, precluding antibiotic window, or mechanical failure in suspected infection), including 5 with ongoing antibiotic therapy for infection in another organ. Six tests were repeated in the same patient and same joint at >6 months’ interval for strong clinical suspicion of infection. The main endpoint was the MSIS score (MusculoSkeletal Infection Society, 2018). ResultsNPV was 98.8%, PPV 72.4%, sensitivity 95.5% and specificity 91%. Prevalence of infection was 19.6%. Only 1 of the 22 infected patients had negative Synovasure™ tests, compared to 81 of the 84 non-infected patients. ConclusionSynovasure™ is a reliable novel diagnostic test, contributing mainly to ruling out infection thanks to its strong NPV. The cost imposes sparing use, but medico-economic assessment would be worthwhile. Level of evidenceIII; prospective of diagnostic performance.

1576. Re-Evaluation of cefepime or piperacillin-tazobactam to Decrease Use of Carbapenems in ESBL-Producing Enterobacterales BloodStream Infections (REDUCE-BSI)

BackgroundThe ideal therapy for treatment of bloodstream infections (BSI) due to ESBL-producing organisms is widely debated. Although prior studies have demonstrated efficacy of non-carbapenems (CBPNs) for ESBL infections, results from the MERINO study group found increased mortality associated with piperacillin/tazobactam (PT) when compared with meropenem for treatment of ESBL BSI. The goal of this study was to investigate patient outcomes associated with the use of CBPN-sparing therapies (PT and cefepime (CEF)) for ESBL BSI. The primary outcome was in-hospital mortality between non-CBPN (PT and CEF) and CBPN groups. Secondary outcomes included clinical cure, microbiologic cure, infection recurrence, and development of resistance.MethodsThis was a retrospective observational study of patients admitted to the hospital from May 2016 - May 2019 with a positive blood culture for an ESBL-producing organism. Patients receiving meropenem, ertapenem, PT, or CEF were included. Patients were excluded if < 18 years old, receiving antibiotics for < 24 hours, treated for a polymicrobial BSI, or receiving concomitant antibiotic therapy for another gram-negative (non-ESBL) infection.ResultsOne hundred and fourteen patients were analyzed; 74 (65%) patients received CBPN therapy compared with 40 (35%) patients that received a non-CBPN (CEF N=30, PT N=10). There were no statistically significant differences in baseline characteristics between groups. The overall in-hospital mortality rate was 6% (N=7). Eight percent of patients (N=6) in the CBPN arm died compared to 3% (N=1) of patients in the non-CBPN arm, P = 0.42. No difference in mortality was detected between groups when evaluating subgroups with Pitt bacteremia score ≥4 (N=25), requiring ICU admission (N=50), non-genitourinary source (N=50), or by causative organism (N=76 E. coli; N=38 Klebsiella spp.). There was no difference between groups for secondary outcomes.ConclusionCEF and PT are reasonable options for the treatment of ESBL BSI and did not result in increased mortality or decreased clinical efficacy when compared to CBPNs in this cohort.Disclosures All Authors: No reported disclosures

Umbilical cord-derived CD362+ mesenchymal stromal cells for E. coli pneumonia: impact of dose regimen, passage, cryopreservation, and antibiotic therapy

BackgroundMesenchymal stromal cells (MSCs) demonstrate considerable promise for acute respiratory distress syndrome (ARDS) and sepsis. However, standard approaches to MSC isolation generate highly heterogeneous cell populations, while bone marrow (BM) constitutes a limited and difficult to access MSC source. Furthermore, a range of cell manufacturing considerations and clinical setting practicalities remain to be explored.MethodsAdult male rats were subject to E. coli-induced pneumonia and administered CD362+ umbilical cord (UC)-hMSCs using a variety of cell production and clinical relevance considerations. In series 1, animals were instilled with E. coli and randomized to receive heterogeneous BM or UC-hMSCs or CD362+ UC-hMSCs. Subsequent series examined the impact of concomitant antibiotic therapy, MSC therapeutic cryopreservation (cryopreserved vs fresh CD362+ UC-hMSCs), impact of cell passage on efficacy (passages 3 vs 5 vs 7 vs 10), and delay of administration of cell therapy (0 h vs 6 h post-injury vs 6 h + 12 h) following E. coli installation.ResultsCD362+ UC-hMSCs were as effective as heterogonous MSCs in reducing E. coli-induced acute lung injury, improving oxygenation, decreasing bacterial load, reducing histologic injury, and ameliorating inflammatory marker levels. Cryopreserved CD362+ UC-hMSCs recapitulated this efficacy, attenuating E. coli-induced injury, but therapeutic relevance did not extend beyond passage 3 for all indices. CD362+ UC-hMSCs maintained efficacy in the presence of antibiotic therapy and rescued the animal from E. coli injury when delivered at 6 h + 12 h, following E. coli instillation.ConclusionsThese translational studies demonstrated the efficacy of CD362+ UC-hMSCs, where they decreased the severity of E. coli-induced pneumonia, maintained efficacy following cryopreservation, were more effective at early passage, were effective in the presence of antibiotic therapy, and could continue to provide benefit at later time points following E. coli injury.

Risk factors for recurrent Clostridium difficile infection among patients in the Clinical Centre of Vojvodina, Serbia: A retrospective clinical trial

Background/Aim. In the last two decades the incidence of recurrent Clostridium difficile infection (CDI) has risen. The aim of this study was to determine the risk factors for the recurrent CDI among patients hospitalized with the initial CDI. Methods. We conducted a retrospective clinical trial at the Clinic for Infectious Diseases, Clinical Center of Vojvodina, Serbia, between January 2010 and January 2016. We enrolled 488 patients with the initial CDI who were treated with oral vancomycin (125 mg, 4 times per day) or oral metronidazole (400 mg, 3 times per day) for 10 days. After the completion of therapy, there was 60 days of the follow-up period for the assessment of the rates of relapse. To determine the risk factors for the CDI relapse, we compared the demographics, clinical and laboratory characteristics of the patients who had a relapse with the patients who had a stable clinical response. Results. Of the 488 cases, 29.09% recurred. The relapse occured in 22.72% patients who received vancomycin and in 36.60% patients treated with metronidazole (p = 0.038). A statistically significant effect on the CDI relapse had the comorbidities such as a malignancies (19.52% vs 8.82%, p = 0.023) and the postoperative CDI (25.67% vs 10.29%, p = 0.035), hipoalbuminemia (&lt; 25 g/L) (70.27% vs 41.94%; p = 0.034) and the concomitant antibiotic therapy (50.67% vs 20.29%; p = 0.031). The persistence of C. difficile toxin in the stool at the end of treatment was registered in 22.32% of patients treated with metronidazole vs 9.09% of patients given vancomycin (p = 0.03). Conclusion. Our data suggest that the important risk factors for the CDI relapse are comorbidities (surgery within a month before developing CDI and malignancy), hipoalbuminemia (&lt; 25g/L) and concomitant non-CDI antibiotics therapy. Vancomycin is more effective than metronidazole in the elimination of C. difficile toxins. The presence of C. difficile toxins in the stool after the successful completion of the initial CDI therapy does not affect significantly the occurrence of relapse.

Conjunctival microflora and its antibiotic sensitivity after serial intravitreal injections

The approach to post-procedure management of patients undergoing intravitreal injections should be unified and consistent. Frequent use of antibiotic drugs leads to generation of resistant conjunctival strains. To study the composition of conjunctival microflora and its antibiotic susceptibility in patients who received 20 or more intravitreal injections and concomitant antibiotic therapy, and in a group of patients of the same age without history of intravitreal injections or ophthalmological operations. A total of 40 inoculations were performed (20 patients in each group, 40 eyes). In case of culture growth, species identification and antibiotic sensitivity of the microorganisms were investigated using automated identification and susceptibility testing system BD Phoenix 100. Culture growth was observed in 70% of the control group patients. All isolated microorganisms were different types of staphylococci - Staphylococcus epidermidis (78.57%), S. caprae (7.14%), S. hominis (7.14%), and S. aureus (7.14%). In the second group, we observed culture growth in 55% of cases. Eleven cultures were Gram-positive bacteria: S. epidermidis (72.73%), S. haemolyticus (18.18%), S. aureus (9.09%). Gram-negative Pseudomonas aeruginosa was detected in 1 patient. In the control group, multi-resistant cultures accounted for 42.86%. In the group of patients with multiple intravitreal injections, 75% of cases showed multiresistance (9 out of 12 isolates). In the group of patients who have undergone 20 or more injections, greatest resistance was observed to penicillin G, doxycycline, gentamicin, erythromycin, clindamycin, moxifloxacin, fusidic acid, chloramphenicol, and trimethoprim/sulfamethoxazole compared to the control group. Overuse of antibiotics in the management of patients receiving intravitreal injections leads to selection of resistant strains.

Diagnostic accuracy of the alpha defensin lateral flow device (Synovasure) for periprosthetic infections in microbiologically complex situations: A study of 42 cases in a French referral centre.

Joint aspiration is currently the reference standard test for diagnosing periprosthetic joint infection (PJI) despite the high rate of false-negative results, of which a major cause is the fastidious nature of some microorganisms. A rapid diagnostic test that detects alpha defensin (Synovasure™, Zimmer, Warsaw, IN, USA) in joint fluid can provide the diagnosis of PJI within a few minutes across the full spectrum of causative organisms (including mycobacteria and yeasts). Its performance in detecting bacterial infections is unaltered by concomitant antibiotic therapy. Few studies of Synovasure™ have been conducted by groups that were involved in designing the test, which has not been validated in France. Assessments in referral centres where complex microbiological situations are common hold considerable interest. The objective of this prospective study was to determine the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and causes of error of Synovasure™ used to diagnose periprosthetic infection in complex microbiological situations. The rapid diagnostic test Synovasure™ has greater than 90% NPV for detecting periprosthetic infections in complex microbiological infections. Synovasure™ was used 42 times in 39 patients between October 2015 and October 2017 in challenging microbiological situations [discordant joint aspiration results (n=20), negative cultures with clinical or laboratory evidence of infection, (n=21), and concomitant antibiotic therapy (n=1)]. Of the 39 patients, 23 had total knee prostheses, 13 total hip prostheses, and 3 total femoral prostheses. The reference standard to which the Synovasure™ results were compared was the PJI criteria set developed by the Musculoskeletal Infection Society (MSIS). Synovasure™ was negative in 30 cases with negative joint fluid cultures (30/42, 71.4%). Of the 12 (28.6%) cases with positive Synovasure™ results, only 7 (7/12, 58.3%) had positive joint fluid cultures. According to the MSIS criteria 9 cases were infected, including 8 with positive and 1 with negative Synovasure™ results. Of the 33 cases that were not infected according to MSIS criteria, 29 had negative and 3 positive Synovasure™ results; the remaining case had a positive Synovasure™ result but was excluded when metallosis was found intra-operatively. NPV was 96.7%, PPV 72.7%, sensitivity 88.9%, and specificity 90.6%. The high NPV of Synovasure™ suggests a role for this test in microbiologically complex situations as a new tool for ruling in and, most importantly, ruling out infection in doubtful cases. III, prospective study of diagnostic accuracy.

Comparison of Outcomes in Outpatient Parenteral Antimicrobial Therapy (OPAT) Patients Receiving Vancomycin vs. Non-Vancomycin Anti-MRSA Therapy

BackgroundThis evaluation set out to determine whether vancomycin therapy was associated with higher rates of clinical failure compared with non-vancomycin anti-methicillin-resistant Staphylococcus aureus therapy (NVAMT) in outpatient parenteral antimicrobial therapy (OPAT).MethodsThis was a retrospective, single center cohort study including patients who received ≥7 days of OPAT with vancomycin, ceftaroline, or daptomycin from January 1, 2009 through March 31, 2016 at the VA Saint Louis Healthcare System. The primary outcome was clinical failure, defined as a composite of acute kidney injury (AKI), creatinine phosphokinase elevations ≥ 500 units/L, adverse drug events necessitating a change in therapy, readmission due to recurrence of infection, or reinitiation of antibiotics after discontinuation. Secondary outcomes were the individual components of the composite primary outcome. Multivariate logistic regression was used to evaluate independent risk factors for clinical failure. Factors evaluated for inclusion in the multivariate model were age >65 at initiation, creatinine clearance >50 mL/minute, length of therapy >28 days, concomitant antibiotic therapy, comorbid disease states, and vancomycin therapy.ResultsA total of 125 patients were included in the analysis – 72 receiving vancomycin and 53 receiving NVAMT. Baseline characteristics between groups were similar, except patients in the NVAMT group had a greater mean serum creatinine and a higher rate of CKD at baseline; 1.53 vs 1.23 (P = 0.032) and 35.9% vs. 19.4% (P = 0.04) respectively. Forty-three percent (31/72) of patients receiving vancomycin achieved clinical failure compared with 54.7% (29/53) of NVAMT patients (P = 0.197). Of the secondary outcomes analyzed, only readmission due to recurrence was significant between groups (vancomycin vs. NVAMT) – 13.8% vs. 30.2% (P = 0.026). In the univariate model only the choice of vancomycin met pre-defined criteria (P < 0.2) for inclusion in the multivariate model. In the multivariate analysis the choice of vancomycin was not found to be significant (0.71 (95% CI 0.33–1.52), P = 0.37).ConclusionVancomycin was not associated with an increased risk of clinical failure when compared with NVAMT in patients receiving OPAT.Disclosures All authors: No reported disclosures.

Effect of an antimicrobial stewardship intervention on outcomes for patients with Clostridium difficile infection.

Although antimicrobial stewardship programs (ASPs) are uniquely positioned to improve treatment of Clostridium difficile infection (CDI) through targeted interventions, studies to date have not rigorously evaluated the influence of ASP involvement on clinical outcomes attributed to CDI. We performed a quasiexperimental study of adult patients with CDI before (n = 307) and after (n = 285) a real-time ASP review was initiated. In the intervention group, an ASP pharmacist was notified of positive CDI results and consulted with the care team to initiate optimal therapy, minimize concomitant antibiotic and acid-suppressive therapy, and recommend surgical/infectious diseases consultation in complicated cases. The primary outcome was a composite of attributable 30-day mortality, intensive care unit admission, colectomy/ileostomy, and recurrence. A higher percentage of patients in the ASP intervention group had acid-suppressive therapy discontinued (30% vs 13%; P < .01). Among patients with severe CDI, more patients in the intervention group received an infectious diseases consultation (17% vs 10%; P = .04), received appropriate therapy with oral vancomycin (87% vs 59%; P <.01), and vancomycin was initiated earlier (mean, 1.1 vs 1.7 days; P <.01). Incidence of the composite outcome was not significantly different between the 2 groups (12.3% vs 14.7%; P = .40). ASP review and intervention improved CDI process measures. A decrease in composite outcomes was not found, which may be due to low baseline rates of attributable complications in our institution.

Pseudoaneurysm of the Right Coronary Artery Masquerading as a Right Atrial Mass

A 63-year-old man under concomitant antibiotic therapy for persistent bronchitis was referred from his general practitioner for progressive dyspnea and associated chest pain. Inflammatory parameters were elevated. Serial cardiac marker enzyme levels, including Troponin I, were within normal values. Thoracic CT-angiogram and echocardiogram showed a 3 cm hyperdense mass in the right atrioventricular groove with focal subepicardial expansion along the lateral atrial wall

Oral teicoplanin for successful treatment of severe refractory Clostridium difficile infection

Clostridium difficile is the leading cause of hospital-acquired diarrhoea. There is no defined protocol for treating severe Clostridium difficile infection (CDI) refractory to vancomycin or vancomycin and metronidazole combination therapy. The aim of this study was to evaluate the rate of clinical cure, time to resolution of diarrhoea and recurrence rate in patients with severe refractory CDI treated with oral teicoplanin. A one-year prospective study was carried out in the Clinic for Infectious and Tropical Diseases, Clinical Center Serbia. Patients with severe and complicated CDI who failed to respond to oral vancomycin and intravenous metronidazole combination therapy were enrolled. They were given oral teicoplanin 100 mg bi-daily. Patients were followed for recurrence for eight weeks. Nine patients with a mean age of 70.8±9.4 years were analyzed. All patients had pseudomembranous colitis, and five had complicated disease. In four patients intracolonic delivery of vancomycin was also performed in addition to oral vancomycin and intravenous metronidazole prior to initiating teicoplanin, but without improvement. After teicoplanin initiation all patients achieved clinical cure. The mean time to resolution of diarrhoea after teicoplanin introduction was 6.3±4.5 days. There was no statistically significant difference in time to resolution of diarrhoea according to initial leucocyte count, age over 65 years, the presence of ileus, complicated disease and the use of concomitant antibiotic therapy (p = 0.652, 0,652, 0.374, 0.374, and 0,548, respectively). None of the patients experienced recurrence. Oral teicoplanin might be a potential treatment for severe and complicated refractory CDI, but further studies are required.

Economic assessment of fidaxomicin for the treatment of Clostridium difficile infection (CDI) in special populations (patients with cancer, concomitant antibiotic treatment or renal impairment) in Spain

The objective of this paper was to assess the cost-utility of fidaxomicin versus vancomycin in the treatment of Clostridium difficile infection (CDI) in three specific CDI patient subgroups: those with cancer, treated with concomitant antibiotic therapy or with renal impairment. A Markov model with six health states was developed to assess the cost-utility of fidaxomicin versus vancomycin in the patient subgroups over a period of 1 year from initial infection. Cost and outcome data used to parameterise the model were taken from Spanish sources and published literature. The costs were from the Spanish hospital perspective, in Euros (€) and for 2013. For CDI patients with cancer, fidaxomicin was dominant versus vancomycin [gain of 0.016 quality-adjusted life-years (QALYs) and savings of €2,397 per patient]. At a cost-effectiveness threshold of €30,000 per QALY gained, the probability that fidaxomicin was cost-effective was 96%. For CDI patients treated with concomitant antibiotic therapy, fidaxomicin was the dominant treatment versus vancomycin (gain of 0.014 QALYs and savings of €1,452 per patient), with a probability that fidaxomicin was cost-effective of 94%. For CDI patients with renal impairment, fidaxomicin was also dominant versus vancomycin (gain of 0.013 QALYs and savings of €1,432 per patient), with a probability that fidaxomicin was cost-effective of 96%. Over a 1-year time horizon, when fidaxomicin is compared to vancomycin in CDI patients with cancer, treated with concomitant antibiotic therapy or with renal impairment, the use of fidaxomicin would be expected to result in increased QALYs for patients and reduced overall costs.