Azithromycin Treatment for Acne Vulgaris: A Case Report on the Risk of Clostridioides difficile Infection.

BACKGROUND Clostridium difficile (C. difficile) is a gram-positive, anaerobic, spore-forming bacillus. It can lead to pseudomembranous colitis characterized by electrolyte disturbances, toxic megacolon, and septic shock. The risk of C. difficile infection is higher with use of certain classes of antibiotics, or when an antibiotic used for a long time. Azithromycin is a macrolide antibiotic known to be safe, with few adverse effects such as diarrhea, stomach pain, and constipation. Azithromycin is currently used for the treatment of acne, with different dosing regimens for patients who cannot receive traditional treatment based on practice guidelines. CASE REPORT A 41-year-old woman was treated with a course of azithromycin 500 mg by mouth 3 times weekly for 6 weeks for acne vulgaris. This was her second antibiotic course of acne treatment within 10 months. A few days after completion of the second azithromycin course, she presented to the clinic with worsening abdominal pain and frequent soft bloody stool. A complete blood count test, C. difficile toxin test, stool culture, and colonoscopy were ordered. She was diagnosed with C. difficile infection confirmed by C. difficile toxin and symptoms. CONCLUSIONS Despite the safety profile of azithromycin, our patient was predisposed to a non-severe case of C. difficile-associated diarrhea, most likely due to the repeated course of the azithromycin regimen that was used to treat her acne vulgaris. This report highlights the importance of managing patients with acne vulgaris according to current practice guidelines, and to report a link between the use of azithromycin as an acne treatment and the occurrence of C. difficile colitis.

Real-world comparison of fidaxomicin versus vancomycin or metronidazole in the treatment of Clostridium difficile infection: a systematic review and meta-analysis.

PURPOSE: There is a lack of real-world evidence of the comparative effectiveness of fidaxomicin versus vancomycin or metronidazole for treating patients with Clostridium difficile (CDI) infection. No systematic evidence comparing these treatment regimens using real-world observational studies was published up to date. The goal of this study is to compare the fidaxomicin and vancomycin/metronidazole regimens in terms of treatment outcomes in CDI patients. METHODS: Systematic and comprehensive search was carried out in the following databases and search engines: EMBASE, Cochrane, MEDLINE, ScienceDirect, and Google Scholar from 1954 until January 2022. Newcastle-Ottawa (NO) scale was used to assess the risk of bias. Meta-analysis was carried out using random effects model, and pooled odds ratios (OR) with 95% confidence interval (CI) were reported. RESULTS: A total of 10 studies satisfied the inclusion criteria, most of them were with poorer quality. The pooled OR was 0.40 (95% CI: 0.09-1.68; I2 = 82.4%) for clinical cure and 2.02 (95% CI: 0.36-11.39; I2 = 88.4%) for sustained cure. We reported pooled OR of 0.69 (95% CI: 0.40-1.20; I2 = 65.7%) for the recurrence rate, 2.81 (95% CI: 1.08-7.29; I2 = 70.6%) for the treatment failure, and 0.73 (95% CI: 0.50-1.07; I2 = 0%) for all-cause mortality between patients that received fidaxomicin and vancomycin. The pooled OR was 0.71 (95% CI: 0.05-9.47; I2 = 69.6%) in terms of recurrence between patients receiving fidaxomicin and metronidazole. CONCLUSION: Fidaxomicin and vancomycin/metronidazole regimens did not have significant difference in terms of treatment outcomes, such as clinical cure, sustained cure, recurrence, and all-cause mortality. However, there was significantly higher risk of treatment failure in CDI patients taking fidaxomicin.

Clostridium difficile infection risk in patients with hidradenitis suppurativa.

Widespread use of antibiotics for hidradenitis suppurativa (HS) opens up the possibility of Clostridium difficile infection (CDI) and an increased risk of mortality. The purpose of this study was to identify risk factors for acquiring CDI in patients with HS. We suggest that providers should take risk factors including increased antibiotic class, hospitalizations, and advanced patient age into consideration when prescribing antibiotics for HS.

Diarrea clostridial. Un patógeno nosocomial a tener en cuenta / Clostridial diarrhea. A nosocomial pathogen to take into account

La diarrea clostridial es una enfermedad aguda con compromiso colónico que puede poner en riesgo la vida de un paciente. Su agente etiológico es el Clostridium difficile y se ha asociado al uso indiscriminado y por largo plazo de antibióticos de amplio espectro. Su cuadro clínico es variable, puede ir desde un cuadro de diarrea hasta la perforación colónica, que puede determinar la realización de una colectomía de urgencia o incluso provocar la muerte del enfermo. El diagnóstico de certeza se realiza mediante la detección de la toxina clostridial en materia fecal, por técnicas de inmunoensayo enzimático. La terapéutica se realiza con metronidazol o vancomicina por vía oral. El tratamiento quirúrgico está indicado ante la presencia de megacolon tóxico o perforación intestinal, y en aquellos pacientes con toxicidad sistémica con fracaso de la terapéutica médica. (AU)

Clostridial diarrhea is an acute disease with colonic involvement that can be life-threatening for a patient. Its etiologic agent is the Clostridium difficile and it has been associated with the indiscriminate and long-term use of broad-spectrum antibiotics. Its clinical picture varies from a picture of diarrhea to colonic perforation that can determine the performance of an emergency colectomy or even the death of the patient. The certainty diagnosis is carried out by detecting clostridial toxin in fecal matter by enzyme immunoassay techniques. The therapy is carried out with metronidazole or vancomycin orally. Surgical treatment is indicated in the presence of toxic mega colon, intestinal perforation or in those patients with systemic toxicity with failure of medical therapy. (AU)

Evaluation of anti-infective-related Clostridium difficile-associated colitis using the Japanese Adverse Drug Event Report database.

Clostridium difficile-associated colitis (CDAC) may cause gastrointestinal illness, ranging in severity from mild diarrhea to fulminant colitis and even mortality. The purpose of this study was to evaluate anti-infective-related CDAC profiles using the Japanese Adverse Drug Event Report (JADER) database. Methods: We selected case reports of adverse events of CDAC as specified in the Medical Dictionary for Regulatory Activities. The association between the number of administered anti-infectives and aging was evaluated using reporting odds ratio (ROR) and adjusted for covariates using multiple-logistic regression. We also evaluated anti-infective-related CDAC-onset profiles using Weibull shape parameter. Results: The JADER database contained 534 688 reports from April 2004 to June 2018. There were 1222 anti-infective related CDAC events. The top five anti-infectives were as follows: third-generation cephalosporins (Anatomical Therapeutic Chemical (ATC) code: J01DD, 313 cases), fluoroquinolones (ATC code: J01MA, 201 cases), macrolides (ATC code: J01FA, 146 cases), carbapenems (ATC code: J01DH, 143 cases), and penicillins with extended spectrum (ATC code: J01CA, 103 cases). The adjusted RORs (95% confidence interval) in individuals using 1, 2, and ≥ 3 anti-infectives were 8.88 (7.05-11.18), 9.77 (6.89-13.86), and 18.39 (11.85-28.54), respectively. Moreover, 47.2% of CDACs occurred within 7 days of anti-infective therapy initiation. The adjusted ROR of interaction terms of ≥ 70 years × 1 drug was 21.81 (14.56-32.68). Conclusion: Our results suggest that the number of administered anti-infectives and patient age are associated with CDAC. These data may be particularly beneficial to prescribers and would contribute to improving the management of CDAC.

Obesity Is Associated with Decreased Risk of Clostridium difficile Infection in Hospitalized Patients with Pouchitis.

BACKGROUND: Clostridium difficile infection (CDI) is one of the leading causes of health-care-associated infections in the USA. There are limited data available regarding CDI in hospitalized patients with inflammatory bowel disease-related ileal pouch. AIMS: This study aimed to evaluate the demographics, clinical features, risk factors, and admission outcomes among hospitalized patients with CDI-related pouchitis (CDP). METHODS: Retrospective chart review was performed for patients who were admitted to our institute for pouchitis between 2013 and 2016 to identify patients with CDP. Logistic regression analysis was performed to assess the risk factors associated with CDP. RESULTS: A total of 160 subjects with pouchitis had a total of 218 admissions during the study period. Primary admission diagnosis was pouchitis or inflammatory bowel disease flare-up for 202 (93%) admissions. Clostridium difficile was tested at least once for 72 patients, and the diagnosis of CDP was established for 16 (10%) patients. All patients with CDP were symptomatic, 13 (81%) had diarrhea, 8 (50%) had abdominal pain, 7 (44%) had nausea/vomiting, and 2 (13%) had gastrointestinal bleeding. On multivariable analysis, only body mass index > 25 (OR 0.25, 95% CI 0.06-0.94, p = 0.048) was significantly associated with decreased risk of CDP. No patients in CDP cohort were admitted to ICU, died at the hospital, or readmitted in 30 days after the discharge. CONCLUSIONS: In our cohort, obesity was associated with low risk of CDP among hospitalized patients with pouchitis. This finding warrants further validation in prospective studies.

Fatal fulminant Clostridioides difficile colitis caused by Helicobacter pylori eradication therapy; a case report.

A 74-year-old male was referred to our critical care department for refractory severe watery diarrhea with advanced leukocytosis (over 70,000/µl) after multiple administrations of eradication therapy against Helicobacter pylori (HP). He was diagnosed as having fulminant colitis due to Clostridioides difficile after antimicrobial eradication therapy. He was given intravenous metronidazole and oral vancomycin. He also received supportive therapy including continuous hemodiafiltration for severe metabolic acidosis. However, despite emergency open sigmoidectomy, he died. The C. difficile isolate recovered was PCR-ribotype 002, which was positive for toxins A and B but negative for binary toxin. HP eradication therapy for prevention of chronic gastritis and stomach cancer is now in widespread use. Although such secondary severe complications are rare, we consider it to be necessary to pay sufficient attention when administering HP eradication therapy.

Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin.

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up. RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant. CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.

Clostridium difficile-associated diarrhea following the therapy with antibiotic and proton pump inhibitors in a 77-year-old man with several comorbidities: A case report.

RATIONALE: Clostridium difficile-associated diarrhea (CDAD) remains a persistent challenge, with substantially increased incidence and severity. The rising burden of CDAD requires urgent identification of preventable risk factors. PATIENTS CONCERNS: A 77-year-old man with the symptoms of abdominal pain and watery diarrhea was readmitted to the hospital, who received cephalosporins and proton pump inhibitors (PPIs) during the initial hospitalization for 12 days until discharge. Antibiotic-associated diarrhea was seriously suspected. And the stool sample was immediately sent for inspection for C difficile. He had a history of chronic bronchitis, coronary heart disease, and osteonecrosis. DIAGNOSIS: CDAD, renal insufficiency INTERVENTIONS:: Oral vancomycin was administered for 14 days. OUTCOMES: On the third day after readmission, the stool sample turned out to be positive for both C difficile toxin and its antigen. After 10-day treatment with vancomycin, diarrhea symptoms disappeared and his stools became normal. LESSONS: In elderly patients with multiple comorbidities, PPIs must be administered cautiously to minimize the risk for adverse effects including CDAD. It is important to identify the preventable risk factors of CDAD for clinicians and pharmacists. Oral vancomycin therapy seems to be effective in CDAD.

Long-term clinical safety of clindamycin and rifampicin combination for the treatment of hidradenitis suppurativa. A Critically Appraised Topic.

CLINICAL QUESTION/SCENARIO: Can therapy with clindamycin and rifampicin be safely continued long term beyond the recommended 10-week course? BACKGROUND: Clindamycin and rifampicin are used in combination to treat hidradenitis suppurativa (HS). There is no data on the efficacy and safety of clindamycin/rifampicin combination therapy for HS beyond 10 weeks. METHODS: We identified the following major concerns that still lack a proper evidenced-based analysis: for rifampicin, drug-induced liver injury, interstitial nephritis, drug interaction and hepatic p450 3A4 enzyme induction; for clindamycin, the concern was community-acquired Clostridium difficile infection (CA-CDI); and experience with long-term treatment. Data sources were used as appropriate to answer the question. Systematic searches were used to assess the risk of CA-CDI and experience with long-term treatment with clindamycin. RESULTS/IDENTIFIED EVIDENCE: The risk for rifampicin-induced liver injury is highest in the first 6 weeks of treatment, whereas interstitial nephritis is primarily observed during intermittent treatment. Enzyme induction due to rifampicin is usually complete after about 2 weeks of treatment and reduces clindamycin blood levels by about 90%. Three meta-analyses identified antibiotic use as a risk factor for CA-CDI. Two of them assigned the highest risk to clindamycin. None of them stratified by length of treatment. There is extensive experience with rifampicin, primarily for the treatment of tuberculosis. Long-term experience with clindamycin is limited. DISCUSSION AND RECOMMENDATION FOR CLINICAL CARE: The analysed risks associated with a combination of clindamycin and rifampicin for hidradenitis suppurative cluster within the first 10 weeks. Treatment can be continued beyond 10 weeks, if clinically necessary.

Clostridium difficile infection and antibiotic-associated diarrhoea.

Antibiotic-associated diarrhoea is among the most common adverse events related to antibiotic use. Most cases are mild, but Clostridium difficile infection causes a spectrum of disease, ranging from occasional diarrhoea to colitis, toxic megacolon, and potentially death. Recent developments in our understanding of the biology of the gut microbiota have provided new insights into the pathogenesis of these conditions, and have revealed a role for manipulation of the gut microbiota as a novel therapeutic approach. This review will give an overview of the assessment of these conditions, before focusing on the rapidly developing area of their treatment.

Feasibility of a Lactobacillus casei Drink in the Intensive Care Unit for Prevention of Antibiotic Associated Diarrhea and Clostridium difficile.

Background: Over 70% of patients are prescribed antibiotics during their intensive care (ICU) admission. The gut microbiome is dramatically altered early in an ICU stay, increasing the risk for antibiotic associated diarrhea (AAD) and Clostridium difficile infections (CDI). Evidence suggests that some probiotics are effective in the primary prevention of AAD and CDI. Aim: To demonstrate safety and feasibility of a probiotic drink in ICU patients. Methods: ICU patients initiated on antibiotics were recruited, and matched with contemporary controls. Study patients received two bottles daily of a drink containing 10 billion Lactobacillus casei which was bolused via feeding tube. Tolerance to probiotics and enteral nutrition, development of adverse events, and incidence of AAD was recorded. CDI rates were followed for 30 days post antibiotic treatment. Results: Thirty-two patients participated in the trial. There were no serious adverse events in the probiotic group, compared to three in the control group. AAD was documented in 12.5% of the probiotic group and 31.3% in the control group. One patient in the probiotic group developed CDI compared to three in the control group. Discussion: A probiotic containing drink can safely be delivered via feeding tube and should be considered as a preventative measure for AAD and CDI in ICU.

Proton pump inhibitors and risk of Clostridium difficile infection: association or causation?

PURPOSE OF REVIEW: The rising burden of Clostridium difficile infection (CDI) requires urgent identification of preventable risk factors. Observational studies suggest an association between proton-pump inhibitor (PPI) use and CDI risk. RECENT FINDINGS: Key historical literature on PPI and CDI associations is reviewed as a prelude to evaluating the plausibility of a causative association. Impactful literature from the past 18 months is examined in detail and critically appraised through the lens of the Bradford Hill Criteria for determination of causality. The PPI and CDI association has been studied extensively and is valid. Nonetheless, causality is not proven due to extensive and difficult to control confounding in observational studies of CDI patient populations with complex comorbidities. SUMMARY: In the authors' opinion, systematic discontinuation of PPIs in patients at risk for CDI is not warranted based on current evidence. Well controlled prospective human studies are needed. Careful and repeated consideration should be given to all PPI prescriptions to avoid potential adverse effects.

A tricyclic pyrrolobenzodiazepine produced by Klebsiella oxytoca is associated with cytotoxicity in antibiotic-associated hemorrhagic colitis.

Cytotoxin-producing Klebsiella oxytoca is the causative agent of antibiotic-associated hemorrhagic colitis (AAHC). Recently, the cytotoxin associated with AAHC was identified as tilivalline, a known pentacyclic pyrrolobenzodiazepine (PBD) metabolite produced by K. oxytoca Although this assertion of tilivalline's role in AAHC is supported by evidence from animal experiments, some key aspects of this finding appear to be incompatible with toxicity mechanisms of known PBD toxins. We therefore hypothesized that K. oxytoca may produce some other uncharacterized cytotoxins. To address this question, we investigated whether tilivalline alone is indeed necessary and sufficient to induce cytotoxicity or whether K. oxytoca also produces other cytotoxins. LC-MS- and NMR-based metabolomic analyses revealed the presence of an abundant tricyclic PBD, provisionally designated kleboxymycin, in the supernatant of toxigenic K. oxytoca strains. Moreover, by generating multiple mutants with gene deletions affecting tilivalline biosynthesis, we show that a tryptophanase-deficient, tilivalline-negative K. oxytoca mutant induced cytotoxicity in vitro similar to tilivalline-positive K. oxytoca strains. Furthermore, synthetic kleboxymycin exhibited greater than 9-fold higher cytotoxicity than tilivalline in TC50 cell culture assays. We also found that the biosynthetic pathways for kleboxymycin and tilivalline appear to overlap, as tilivalline is an indole derivative of kleboxymycin. In summary, our results indicate that tilivalline is not essential for inducing cytotoxicity observed in K. oxytoca-associated AAHC and that kleboxymycin is a tilivalline-related bacterial metabolite with even higher cytotoxicity.

An unexpected complication following uterine artery embolisation.

A 35-year-old nulliparous woman underwent uterine artery embolisation (UAE) for heavy menstrual bleeding and anaemia due to fibroids, refractive to medical and surgical treatment.Bilateral UAE was performed after cephazolin prophylaxis and analgesia. Postoperatively, pain and abdominal bloating were prominent. Symptoms were initially treated as postembolisation syndrome, and analgesia was escalated. By the third day, pain was worsening and the woman developed marked tachypnoea and tachycardia, with raised inflammatory markers and lactate. An abdominal X-ray and CT showed dilated colon. A colonoscopy demonstrated severe mucosal ulceration down to the muscular layer.A subtotal colectomy and end ileostomy formation was performed with intraoperative findings of toxic megacolon with near perforation. The cause of the toxic megacolon, in the absence of previous bowel pathology, was attributed to pseudomembranous colitis as a consequence of single dose prophylactic antibiotic.

Protection of Hamsters from Mortality by Reducing Fecal Moxifloxacin Concentration with DAV131A in a Model of Moxifloxacin-Induced Clostridium difficile Colitis.

Lowering the gut exposure to antibiotics during treatments can prevent microbiota disruption. We evaluated the effects of an activated charcoal-based adsorbent, DAV131A, on the fecal free moxifloxacin concentration and mortality in a hamster model of moxifloxacin-induced Clostridium difficile infection. A total of 215 hamsters receiving moxifloxacin subcutaneously (day 1 [D1] to D5) were orally infected at D3 with C. difficile spores. They received various doses (0 to 1,800 mg/kg of body weight/day) and schedules (twice a day [BID] or three times a day [TID]) of DAV131A (D1 to D8). Moxifloxacin concentrations and C. difficile counts were determined at D3, and mortality was determined at D12 We compared mortality rates, moxifloxacin concentrations, and C. difficile counts according to DAV131A regimen and modeled the links between DAV131A regimen, moxifloxacin concentration, and mortality. All hamsters that received no DAV131A died, but none of those that received 1,800 mg/kg/day died. Significant dose-dependent relationships between DAV131A dose and (i) mortality, (ii) moxifloxacin concentration, and (iii) C. difficile count were evidenced. Mathematical modeling suggested that (i) lowering the moxifloxacin concentration at D3, which was 58 µg/g (95% confidence interval [CI] = 50 to 66 µg/g) without DAV131A, to 17 µg/g (14 to 21 µg/g) would reduce mortality by 90%; and (ii) this would be achieved with a daily DAV131A dose of 703 mg/kg (596 to 809 mg/kg). In this model of C. difficile infection, DAV131A reduced mortality in a dose-dependent manner by decreasing the fecal free moxifloxacin concentration.

Cephalosporins Associated Pseudomembraneous Colitis in an Elderly Male Patient - A Case Report.

INTRODUCTION: Incidence of antibiotic- associated diarrhoea is a common (10-30%) but pseudomembranous colitis (PMC) is less frequent (1-5%). Fluoroquinolones, clindamycin, penicillins, cephalosporins (mostly third generation) are commonly associated with PMC. The association between cephalosporins and PMC is now well established. CASE PRESENTATION: A 78 year old male patient developed pseudomembraneous colitis after administration of Ceftriaxone and Cefazoline for the treatment of pleural effusion. The reaction was confirmed by ultrasonography and CT scan. Causative agents were stopped and patient was managed by systemic therapy. Patient was expired due to respiratory complications as there was complexity in management of disease due to development of pseudomembraneous colitis. CONCLUSION: Increase awareness of prescribers for high-risk drugs, close monitoring, with immediate withdrawal of the culprit drug can reduce the complexity of management that occur due to development of such adverse drug reaction.