Concurrent Use Of Antibiotics Research Articles

Antibiotic Exposure Concurrently with Anti-PD1 Blockade Therapy Reduces Overall Survival in Patients with Child-Pugh Class A Advanced Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide with a poor prognosis. Treatment with immune checkpoint inhibitors (ICIs) has improved overall survival in patients with HCC. However, not all patients benefit from the treatment. In this study, 59 patients with HCC were enrolled from two medical centers in Saudi Arabia, with 34% using antibiotics concurrently with their Nivolumab (anti-PD1 blockade). The impact of antibiotic use on the clinical outcomes of patients with HCC undergoing treatment with anti-PD1 blockade was examined. The patients' overall survival (OS) was 5 months (95% CI: 3.2, 6.7) compared to 10 months (95% CI: 0, 22.2) (p = 0.08). Notably, patients with Child-Pugh A cirrhosis receiving anti-PD1 blockade treatment without concurrent antibiotic use showed a significantly longer median OS reaching 22 months (95% CI: 6.5, 37.4) compared to those who were given antibiotics with a median OS of 6 months (95% CI: 2.7, 9.2) (p = 0.02). This difference in overall survival was particularly found in Child-Pugh class A patients receiving anti-PD1 blockade. These findings suggest that antibiotic use may negatively affect survival outcomes in HCC patients undergoing anti-PD1 blockade, potentially due to antibiotic-induced alterations to the gut microbiome impacting the anti-PD1 blockade response. This study suggests the need for careful consideration when prescribing antibiotics to patients with HCC receiving anti-PD1 blockade.

Utilization of Prophylactic Antibiotics for Cardiac Patients Undergoing Dental Procedures in Saudi Arabia: A Retrospective Study.

This study aimed to determine the characteristics of antibiotic prophylaxis (AP) utilization and the level of adherence of King Saud University Medical City (KSUMC) staff to the latest American Heart Association (AHA) guidelines for AP for infective endocarditis (IE) in cardiac patients undergoing dental procedures. The study was conducted as a retrospective cohort study to investigate the relationship between AP in dental procedures and cardiac patients admitted in the surgical wards of KSUMC between 2015 and 2021. All cardiac patients who underwent dental procedures were included in the study. We excluded patients with long-term or concurrent antibiotic use for other indications. Overall, 170 (69.4%) cardiac patients received AP before undergoing a dental procedure. The most common comorbidities were hypertension (39.1%) and diabetes (34.2%). Most of the low-risk (69.4%) and moderate-risk (70.5%) patients received AP, despite the guideline's recommendation to limit AP to high-risk patients only. Moreover, only 53.8% of high-risk patients were prescribed AP. In total, 95.9% of the 170 patients who received AP did so without following the recommendations. Only one patient developed IE during the 1-year follow-up. Tooth extraction was the only significant predictor of AP prescription in our study (P = 0.001; OR: 3.73; 95% CI; 1.678-8.298). There was an exceeding level of inconsistency (95.9%) in AP utilization by cardiac patients in our sample compared with the recommendations of the latest AHA guidelines.

An unusual case of orbital abscess due to Morganella morganii and Klebsiella pneumoniae, following acute on chronic dacryocystitis

Orbital abscess secondary to dacryocystitis is rare.[1] Morganella morganii is a gram-negative rod and a facultative anaerobic enteric bacterium causing opportunistic infection, often isolated as a cause of nosocomial infection, specifically in urinary tract or wound infections. Risk factors may be old age, presence of concomitant bacteremia, hospitalization, recent surgery, concurrent antibiotic use, and immunocompromised hosts.[2] According to authors' knowledge, till date, only one case of orbital abscess due to M. morganii has been reported secondary to sinusitis. There are no reports of orbital abscess due to M. morganii following dacryocystitis till date.[3] We report a rare case of orbital abscess secondary to dacrocystitis caused by M. morganii and Klebsiella pneumoniae in an immunocompetent patient.

Acute ischemic colitis associated with oral decongestant use: a systematic review

Acute ischemic colitis (IC) has been linked with the use of oral decongestants. However, clinical evidence on this association remains limited. We aim to evaluate the occurrence and clinical outcomes of acute IC following over-the-counter (OTC) use of pseudoephedrine and phenylephrine.We conducted a systematic review of the MEDLINE, Google Scholar, Scopus, and Embase databases between inception and July 20, 2022. Specific search terms were used. The inclusion criteria consisted of English-language articles describing acute IC secondary to pseudoephedrine or phenylephrine.A total of 18 case reports (level of clinical evidence: IV) fulfilled our inclusion criteria. The mean age of patients was 51.6 ± 15.3 years, with 14 (77.8%) cases reported in women. The clinical presentation was mainly related to abdominal pain 16 (88.9%), hematochezia 15 (83.3%), and/or abdominal tenderness 10 (55.6%). The medical background showed that 5 (27.8%) patients were previously healthy. In the 13 (72.2%) patients with comorbidities, hypertension 6 (46.2%), a history of tobacco use 5 (38.5%), and psychiatric illnesses 4 (30.8%) were commonly reported. Leukocytosis was encountered in 13 (72.2%) patients. Diagnostic investigations included a combination of computed tomography scan and colonoscopy in 10 (55.6%), colonoscopy alone in 6 (33.3%), and flexible sigmoidoscopy in 1 (5.6%) patient. Colonoscopic biopsy was the mainstay of diagnosis in 15 (83.3%) patients. Treatment was based on supportive care in 18 (100%), concurrent antibiotic use in 2 (11.1%), and surgical intervention in 1 (5.6%) patient. Recurrent episodes of IC occurred in 4 (22.2%) patients.Acute IC secondary to oral decongestants remains a rare but important clinical phenomenon. Clinical suspicion and imaging findings are important for the early diagnosis.In unexplained cases of IC, clinicians should specifically inquire about oral decongestants since they are OTC and patients commonly fail to reveal their usage. These drugs should be avoided for transient cold symptoms, especially in women.

Clinical Impact of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Associated Clostridioides difficile Infection Among Patients with Lung Cancer.

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs)-associated Clostridioides difficile infection (CDI) among lung cancer patients have been reported in case reports and adverse events reporting system databases in the United States and Japan, but clinical data remained insufficient. This study aims to evaluate CDI in lung cancer patients receiving EGFR-TKIs. We conducted a retrospective cohort study using multi-institutional electronic medical records database. We included patients aged older than 20 years diagnosed with lung cancer and treated with EGFR-TKIs (gefitinib, erlotinib, afatinib). We defined EGFR-TKI initiation date as the index date and occurrence of diarrhea with CDI or without CDI as the event date. We followed patients from the index date until the event date, ICU admission, death, or 12/31/2019. We included 2242 diarrhea patients, 51 were EGFR-TKI with CDI cohort, and 2191 were diarrhea without CDI cohort. Patients who were concurrently taking antibiotics (hazard ratio [HR], 3.30; 95% CI, 1.67-6.5) and systemic steroids (HR, 4.9; 95% CI, 2.65-9.06) had an increased risk of CDI. First-generation EGFR-TKIs tended to be associated with an increased risk of CDI compared with afatinib (HR, 1.81, 95% CI, 0.94-3.47). EGFR-TKI with CDI had a higher ICU admission rate (HR, 3.42, 95% CI, 1.98-5.91) and mortality rate (HR, 2.34, 95% CI, 1.67-3.28) than diarrhea without CDI. Patients with CDI had higher ICU admission rates and mortality rates than those without CDI. Concurrent use of antibiotics and systemic steroids were risk factors for CDI among patients with lung cancer receiving EGFR-TKIs. Afatinib was not associated with a higher risk of CDI than first-generation EGFR-TKIs.

Effect of an ear cleaner instillation containing lipacids in a model of re-acidification of the external auditory canal in dogs.

BackgroundIn humans, the acidic pH of the ear canal plays a protective role against infection and a change towards alkalinity of the external auditory canal (EAC) is a local factor in the progression of acute to chronic otitis externa (OE). The use of acidic preparations alone for treatment of OE without concurrent antibiotic use is well‐documented in humans. In dogs, only one study has investigated the EAC pH in healthy dogs and in dogs with OE, and investigations to understand the role of EAC pH in the pathogenesis of canine OE are lacking.Hypothesis/objectivesTo obtain physiological EAC pH values in beagle dogs. To develop a model of re‐acidification of the EAC in dogs and to investigate how an acidic solution may accelerate the return to a physiological pH.AnimalsTen healthy beagle dogs in a laboratory setting.Materials and MethodsA model of re‐acidification of the EAC was developed by instillation of a pH 10.1 phosphate‐buffered saline (PBS) solution and the subsequent acidic effect of an ear cleaner containing lipacids was evaluated in this model.ResultsMean physiological EAC pH was 6.12 (± 0.36). EAC re‐acidification took up to 9 h in this model. Mean pH values dropped immediately to 6.38 (± 0.27) on ears treated with an acidic ear cleaner. No abrupt drop was observed of the mean pH values for the control ears.Conclusion and clinical importanceThis study confirms that physiological EAC pH in dogs is acidic. This model of re‐acidification of the EAC pH allows investigations on acidic properties of topical ear products in healthy ears.

The Benefits and Harms of Cleansing for Acute Traumatic Wounds: A Narrative Review.

Acute traumatic wound cleansing is currently a controversial issue demonstrated by the variability in solutions and techniques used to clean wounds in clinical practice. Although there is evidence of improved infection outcomes in wounds cleansed with antiseptics, these observations are often undermined by concurrent use of antibiotics in addition to poor study design. Cleansing techniques including pressurized irrigation have also been investigated indicating potential harms such as edema and inconsistencies in irrigation pressures. The purpose of this article is to provide a narrative review on the contemporary evidence indicating the potential harms and benefits of wound cleansing in the context of acute traumatic wounds.This literature review reveals that acute wound cleansing in clinical practice remains heavily dependent on tradition rather than robust clinical evidence. The evidence base remains limited because of methodological and pragmatic issues in obtaining definitive data on the efficacy of specific agents and techniques. Future studies should focus on establishing the relative benefits of different cleansing solutions and techniques. Establishing the most effective use of antiseptic cleansing solutions may also help reduce further antimicrobial resistance as observed in recent studies. Clinicians responsible for cleansing wounds must consider patient preference when deciding which solution and techniques are used. In addition, a risk assessment considering the potential harms and benefits of different solutions and techniques must be performed.

Use of Antibiotics during Immune Checkpoint Inhibitor Treatment Is Associated with Lower Survival in Hepatocellular Carcinoma

Background: Recent studies suggested that use of antibiotics may interfere with treatment responses to immune checkpoint inhibitors (ICIs). We determined whether concurrent use of antibiotics during ICI therapy was associated with adverse outcomes in patients with advanced hepatocellular carcinoma (HCC). Methods: This is a territory-wide retrospective cohort study including all advanced HCC patients who received ICIs (nivolumab, pembrolizumab, or ipilimumab) between January 2014 and December 2019. Exclusion criteria included prior liver transplantation and use of cabozantinib, regorafenib, or ramucirumab. The exposure of interest was concurrent antibiotic use within 30 days before or after the commencement of ICI. The adjusted hazard ratio (aHR) of cancer-related mortality and all-cause mortality with antibiotic use was derived by propensity score (PS) matching in 1:2 ratio of covariates including baseline characteristics, causes of cirrhosis, Child-Pugh status, prior HCC treatment, comorbidities, concurrent medications, and laboratory results including alpha fetoprotein. Results: A total of 395 HCC patients who had received ICIs were included. During a median follow-up of 16.5 months (interquartile range [IQR]: 5.6–44.3), there were 286 (72.4%) deaths including 231 cancer-related deaths. The median time from the first ICI to event was 7.7 months (IQR: 4.0–16.8). PS matching of 56 antibiotic users with 99 nonusers showed that concurrent antibiotic use with ICI was associated with higher cancer-related (aHR: 1.66; 95% CI: 1.08–2.54) and all-cause mortality (aHR: 1.63; 95% CI: 1.17–2.28). Conclusions: Concurrent antibiotic use during immunotherapy was associated with higher mortality in patients with advanced HCC. Further studies should examine the role of gut dysbiosis on responses to ICI.

1196. Influence of antibiotic use on the effectiveness and safety of immune checkpoint inhibitors in Japan

BackgroundIt has been reported that antibiotic use changes the gut microbiome and alters the outcome of treatment with immune checkpoint inhibitors (ICIs). However, in Asia, this has not been well studied, and there is insufficient evidence to support these reports.MethodsIn this study, we investigated the concurrent use of antibiotics and the administration of PD-1 inhibitors in Japanese patients, and examined the relationship between antibiotics and the clinical benefit or safety of PD-1 inhibitors.ResultsIn total, 152 patients were analyzed: 62 patients received systemic antibiotics within 2 months before or 1 month after the first dose of PD-1 inhibitors (the antibiotic group); the remaining patients comprised the non-antibiotic group. There was a significantly higher proportion of patients under 65 years of age in the antibiotic group. Overall survival (OS) was not reached in the antibiotic and non-antibiotic groups, and there was no statistically significant difference between the two groups (HR = 1.48) (Figure 1). Progression-free survival (PFS) was 3.29 months in the antibiotic group and was significantly shorter than that in the non-antibiotic group (5.99 months, HR = 1.75) (Figure 2). Multivariate analysis by Cox regression analysis also showed that PFS was shorter in the antibiotic group (HR=1.63). As age may be a confounding factor, we performed a stratified analysis, a common method used to adjust for bias. The results of the stratified log-rank test after adjustment for age showed that the PFS was significantly shorter in the antibiotic group. There were no statistically significant differences between the two groups in the response rate, incidence of adverse events of Grade 3 or above, and laboratory data (Table 1).Figure 1 Figure 2 Table 1 ConclusionOur results suggest that the use of antibiotics may affect the anticancer treatment outcomes of Japanese patients who are administered PD-1.Disclosures All Authors: No reported disclosures

Effect of antibiotic use prior to or concurrent with immune checkpoint inhibitors on outcomes in patients with Hodgkin lymphoma.

8030 Background: There is growing interest in the identification of modifiable patient-specific factors that may predict response to immune checkpoint inhibitors (ICIs) in classical Hodgkin lymphoma (cHL). Recently, it has been proposed that antibiotic use could decrease the efficacy of ICIs in the treatment of advanced solid malignancies. The objective of our study is to assess whether antibiotic use prior to or concurrent with ICIs is associated with changes in outcomes in patients with cHL. Methods: Patients who received a PD-1 or CTLA-4 blocker for the treatment of cHL at Mayo Clinic Rochester between January 1, 2011 and October 20, 2018 were identified. We conducted a longitudinal retrospective chart review to identify those who received antibiotics within 30 or 90 days prior to initiation or concurrent with ICI therapy. Univariate cox regression analysis was used to assess for an association between antibiotic use and overall survival (OS) and progression-free survival (PFS) within these groups; a time-dependent variable was used for concurrent antibiotic use. Results: A total of sixty-two patients were identified (61% male, median age at ICI initiation 35 years [range: 19-87]). Median duration of follow up from ICI start was 38 months (range: 4-78). Twenty-one patients (34%) received antibiotics within 90 days of initiation of ICI, of which thirteen (21%) received antibiotics within 30 days. Thirty-five patients (57%) received antibiotics concurrently with ICI. Concurrent and prior antibiotic use within 90 days of ICI were both associated with inferior PFS (concurrent HR = 6.38 [95% CI 3.02-13.47]; 90-day HR = 2.21 [95% CI 1.10-4.47]) and OS (concurrent HR = 8.77 [95% CI 1.91-40.36]; 90-day HR = 2.96 [95% CI 1.09-8.04]). Conclusions: Antibiotic use is associated with inferior outcomes in patients with cHL treated with ICIs in this single institution cohort. This may reflect potential antibiotic effects on the gut microbiome (GMB) and immune system as has been suggested in prior studies. Further confirmatory studies and examination of potential confounding covariates are needed.

Decreased Fecal Bacterial Diversity and Altered Microbiome in Children Colonized With Clostridium difficile.

The gut microbiome is believed to play a role in the susceptibility to and treatment of Clostridium difficile infections (CDIs). It is, however, unknown whether the gut microbiome is also affected by asymptomatic C difficile colonization. Our study aimed to evaluate the fecal microbiome of children based on C difficile colonization, and CDI risk factors, including antibiotic use and comorbid inflammatory bowel disease (IBD). Subjects with IBD and non-IBD controls were prospectively enrolled from pediatric clinics for a biobanking project (n = 113). A fecal sample was collected from each subject for research purposes only and was evaluated for asymptomatic toxigenic C difficile colonization. Fecal microbiome composition was determined by 16S rRNA sequencing. We found reduced bacterial diversity and altered microbiome composition in subjects with C difficile colonization, concurrent antibiotic use, and/or concomitant IBD (all P < 0.05). Accounting for antibiotic use and IBD status, children colonized with C difficile had significant enrichment in taxa from the genera Ruminococcus, Eggerthella, and Clostridium. Children without C difficile had increased relative abundances of Faecalibacterium and Rikenellaceae. Imputed metagenomic functions of those colonized were enriched for genes in oxidative phosphorylation and beta-lactam resistance, whereas in the subjects without C difficile, several functions in translation and metabolism were over-represented. In children, C difficile colonization, or factors that predispose to colonization such as antibiotic use and IBD status were associated with decreased gut bacterial diversity and altered microbiome composition. Averting such microbiome alterations may be a method to prevent or treat CDI.

Usage of antibiotics in the intensive care units of an academic tertiary-level hospital

Background: The post-antibiotic era is approaching fast as multidrug-resistant bacteria emerge and the antibiotic pipeline slows to a trickle. Antibiotic stewardship requires that antibiotics be used appropriately and as such this study reviewed the utilisation of antibiotics in five adult intensive care units (ICUs) at Charlotte Maxeke Johannesburg Academic Hospital.Methods: A retrospective, cross-sectional record review of admissions to the Coronary, Cardiothoracic, Multidisciplinary, Neurology and Trauma ICUs was conducted over one month. Information from the ICU chart was captured on a modified version of the South African Antibiotic Stewardship Programme, Antibiotic Prescription Chart.Results: A total of 204 files were reviewed with 55.2% of patients receiving antibiotics during admission. The three most frequently prescribed were amoxicillin clavulanate (n = 46), piperacillin/tazobactam (n = 32) and cefazolin (n = 28), while colistin was used on one occasion. The majority of antibiotics (84.9%) were given for five days or less. Of concern however, of 35 instances where concurrent administration of antibiotics occurred, 8 had a similar spectrum and on 7 occasions the duration of antibiotic treatment was longer than 7 days. Cultures were ordered on 228 occasions. In patients receiving antibiotics 61.6% had cultures ordered; however, only 56.3% of these were taken before or on the day that antibiotics were started.Conclusion: This study showed that generally the duration of antibiotic treatment was short, concurrent use of antibiotics was minimal and the use of a restricted formulary limited the use of specific antibiotics such as colistin. However, implementation of stewardship principles and ordering of appropriate cultures would assist in further improving appropriate use of antibiotics in the ICU setting.

Clostridium difficile ribotype 027: relationship to age, detectability of toxins A or B in stool with rapid testing, severe infection, and mortality.

Clostridium difficile infection (CDI) can cause severe disease and death, especially in older adults. A better understanding of risk factors for adverse outcomes is needed. This study tests the hypotheses that infection with specific ribotypes and presence of stool toxins independently associate with severity and constructs predictive models of adverse outcomes. Cases of non-recurrent CDI were prospectively included after positive stool tests for toxins A and/or B by enzyme immunoassay (EIA) or tcdB by polymerase chain reaction. Outcomes included severe CDI (intensive care unit admission, colectomy, or death attributable to CDI within 30 days of diagnosis) and 30-day all-cause mortality. Adjusted models were developed to test hypotheses and predict outcomes. In total, 1144 cases were included. The toxin EIA was positive in 37.2% and 35.6% of patients were of age >65 years. One of the 137 unique ribotypes was ribotype 027 (16.2%). Detectable stool toxin did not associate with outcomes. Adjusting for covariates, including age, Ribotype 027 was a significant predictor of severe CDI (90 cases; odds ratio [OR], 1.73; 95% confidence interval [CI], 1.03-2.89; P = .037) and mortality (89 cases; OR, 2.02; 95% CI, 1.19-3.43; P = .009). Concurrent antibiotic use associated with both outcomes. Both multivariable predictive models had excellent performance (area under the curve >0.8). Detection of stool toxin A and/or B by EIA does not predict severe CDI or mortality. Infection with ribotype 027 independently predicts severe CDI and mortality. Use of concurrent antibiotics is a potentially modifiable risk factor for severe CDI.

Increased frequency of peripheral venipunctures raises the risk of central-line associated bloodstream infection in neonates with peripherally inserted central venous catheters.

Central-line associated bloodstream infection (CLA-BSI), which is mostly caused by coagulase-negative staphylococcus, is an important morbidity in neonatal intensive care units. Our study is aimed to identify the risk factors of CLA-BSI in neonates with peripherally inserted central venous catheters (PICCs). A retrospective cohort study of neonatal intensive care unit patients with a PICC insertion between January 1, 2011 and December 31, 2012 was conducted. We performed univariate and multivariate analyses with a logistic regression model to investigate the risk factors and the association between increased frequency of peripheral venipunctures during PICC use and the risk of CLA-BSI while adjusting for other variables. There were 123 neonates included in our study. Thirteen CLA-BSIs were recorded within the follow-up period. The incidence of PICC-associated CLA-BSI was 4.99 per 1000 catheter-days. There was no statistically significant association between the risk of CLA-BSI and gestational age, birth weight, chronological age, or other comorbidities. However, the odds of CLS-BSI increased to 12 times if the patient received six or more venipunctures within the period without concurrent antibiotic use [odds ratio (OR), 11.94; p < 0.001]. The OR of CLA-BSIs increased by 16% per venipuncture during PICC use (OR, 1.14; p = 0.003). During PICC use, increased frequency of venipunctures, especially when there was no concurrent antibiotic use, substantially raises the risk of CLA-BSI. By decreasing unnecessary venipunctures during PICC use, PICC-associated CLA-BSI and further morbidities and mortalities can be prevented.

Morphologic Predictors of a Microbiological Yield in Patients With a Tree-in-Bud Pattern on Computed Tomography

To evaluate the computed tomographic (CT) predictors of a clinically significant yield from microbiological tests in patients with a tree-in-bud pattern. CT examinations in 53 patients (male=34; mean age=52.9 ± 17.3 y) with a tree-in-bud pattern in whom a diagnostic test (sputum analysis, bronchoalveolar lavage or nasopharyngeal aspirates) had been performed within 2 weeks were identified. The following CT patterns were independently quantified by 2 thoracic radiologists: tree-in-bud, bronchiectasis, bronchial wall thickening, consolidation, ground-glass opacification, and nodules. The presence of cavitation (in nodules and/or consolidation) was recorded. Patient charts were reviewed for the presence of a clinically significant positive microbiological result. A clinically significant causal organism was present in 25/53 (47%) patients. The median extent of a tree-in-bud pattern was 5 [range=1 to 16 (maximum range=0 to 18)], and cavitation was present in 14/53 (26%) patients (cavitating nodules=8, cavitation in consolidation=3, and cavitation in consolidation and nodules=3). There was no independent linkage between the extent of a tree-in-bud pattern and the identification of a clinically significant organism. The microbiological yield was significantly higher if there was coexistent cavitation in nodules or consolidation [11/14 (79%) vs. 14/39 (39%); P=0.005]. On stepwise logistic regression, the only CT predictor of a clinically significant microbiological yield was cavitation on CT (odds ratio=9.7; 95% confidence interval=1.9, 49.9; P<0.01); the extent of a tree-in-bud pattern, concurrent use of antibiotics, age, and sex were not independently linked to a significant microbiological yield. A specific clinically significant microbiological diagnosis was obtained in approximately 50% of patients with a tree-in-bud pattern. The microbiological yield rises strikingly when a tree-in-bud pattern coexists with cavitation (in nodules or consolidation) but is not predicted by ancillary CT signs or clinical parameters.

Mathematical model to quantify the effects of risk factors on carbapenem-resistant Acinetobacter baumannii.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections are increasing, and they are associated with an increased risk of mortality in hospitalized patients. Linear regression is commonly used to identify concurrent trends, but it cannot quantify the relationship between risk factors and resistance. We developed a model to quantify the impact of antibiotic consumption on the prevalence of CRAB over time. Data were collected from January 2007 to June 2013 from our institution. Quarterly antibiotic consumption was expressed as defined daily dose/1,000 inpatient days. Six-month prevalence of CRAB was expressed as a percentage of all nonrepeat A. baumannii isolates tested. Individual trends were identified using linear regression. Antibiotic consumption from 2007 to 2011 was input as a step function in a relationship with CRAB. Model fit was evaluated by visual inspection and the residual sum of squares. The final model was validated using the best-fit (95% confidence interval) parameter estimates and antibiotic consumption to predict CRAB prevalence from January 2012 to June 2013. Cefepime, ertapenem, and piperacillin-tazobactam consumption and CRAB prevalence increased significantly over time. CRAB prevalence was best correlated to ertapenem (use sensitive; r2=0.76), and accounting for additional concurrent antibiotic use did not significantly improve model fit. Prospective validation with ertapenem consumption correlated well with CRAB observations, suggesting good predicting ability of the model. Our model provided the quantitative impact of antibiotic consumption on CRAB. We plan to further refine this model to account for multiple risk factors. Interventions should focus on controlling risk factors with the highest impact on resistance.

Risk of bleeding and antibiotic use in patients receiving continuous phenprocoumon therapy

There is major concern about coumarins interacting with various drug classes and increasing the risk of overanticoagulation. The aim of the study was to assess bleeding risk in patients with concurrent use of antibiotics and phenprocoumon, the most widely prescribed coumarin in many European countries. We conducted a nested-case-control study within a cohort of 513,338 incident and continuous phenprocoumon users ≥ 18 years of age using claims data of the statutory health insurance company AOK, covering 30% of the German population. Bleeding risk associated with current use of antibiotics for systemic use (antibacterials/antimycotics) was calculated using conditional logistic regression in 13,785 cases with a bleeding event and 55,140 risk-set sampling-matched controls. Bleeding risk associated with any antibacterial use in phenprocoumon users was significantly increased [odds ratio (OR) 2.37, 95% confidence interval (CI) 2.20-2.56]. The association was stronger for gastrointestinal than for cerebral bleeding (OR 2.09, 95% CI 1.84-2.38 and OR 1.34, 95% CI 1.03-1.74, respectively) and highest for other/unspecified bleeding (OR 2.92, 95% CI 2.62-3.26). Specific antibiotic classes were strongly associated with bleeding risk, e.g. cotrimoxazole (OR 3.86, 95% CI 3.08-4.84) and fluorquinolones (OR 3.13, 95% CI 2.74-3.59), among those highest for ofloxacin (OR 5.00, 95% CI 3.01-8.32). Combined use of phenprocoumon and antimycotics was not significantly associated with bleeding risk. Risk was not significantly modified by age (pint=0.25) or sex (pint=0.96). The association was stronger the closer the antibiotic exposure was to the bleeding event. Among continuous phenprocoumon users, antibiotics - particularly quinolones and cotrimoxazole - should be prescribed after careful consideration due to an increased bleeding risk. Close monitoring of international normalised ratio levels after prescription is recommended.

Herpesviruses and the microbiome

The focus of this article will be to examine the role of common herpesviruses as a component of the microbiome of atopic patients and to review clinical observations suggesting that atopic patients might be predisposed to more severe and atypical herpes-related illness because their immune response is biased toward a TH2 cytokine profile. Human populations are infected with 8 herpesviruses, including herpes simplex virus HSV1 and HSV2 (also termed HHV1 and HHV2), varicella zoster virus (VZV or HHV3), EBV (HHV4), cytomegalovirus (HHV5), HHV6, HHV7, and Kaposi sarcoma-associated herpesvirus (termed KSV or HHV8). Herpesviruses are highly adapted to lifelong infection of their human hosts and thus can be considered a component of the human "microbiome" in addition to their role in illness triggered by primary infection. HSV1 and HSV2 infection and reactivation can present with more severe cutaneous symptoms termed eczema herpeticum in the atopic population, similar to the more severe eczema vaccinatum, and drug reaction with eosinophilia and systemic symptoms syndrome (DRESS) is associated with reactivation of HSV6 and possibly other herpesviruses in both atopic and nonatopic patients. In this review evidence is reviewed that primary infection with herpesviruses may have an atypical presentation in the atopic patient and conversely that childhood infection might alter the atopic phenotype. Reactivation of latent herpesviruses can directly alter host cytokine profiles through viral expression of cytokine-like proteins, such as IL-10 (EBV) or IL-6 (cytomegalovirus and HHV8), viral encoded and secreted siRNA and microRNAs, and modulation of expression of host transcription pathways, such as nuclear factor κB. Physicians caring for allergic and atopic populations should be aware of common and uncommon presentations of herpes-related disease in atopic patients to provide accurate diagnosis and avoid unnecessary laboratory testing or incorrect diagnosis of other conditions, such as drug allergy or autoimmune disease. Antiviral therapy and vaccines should be administered promptly when indicated clinically.

Risk of Clostridium difficile Infection With Acid Suppressing Drugs and Antibiotics: Meta-Analysis

Several studies have raised concern regarding the possible association between proton-pump inhibitors (PPIs) and Clostridium difficile infection (CDI). We aimed to perform a systematic review of incident and recurrent CDI in PPI users, and to evaluate the relative impact of concurrent antibiotic use, or switching acid suppression to histamine-2-receptor antagonists (H2RAs). We searched MEDLINE and EMBASE from inception to December 2011 for controlled observational studies that reported on the risk of CDI with and without PPI use. We performed random effects meta-analysis and assessed statistical heterogeneity using the I(2) statistic. We included 42 observational studies (30 case-control, 12 cohort) totalling 313,000 participants overall. Pooled analysis of 39 studies showed a statistically significant association between PPI use and risk of developing CDI, odds ratio (OR) 1.74 (95% confidence interval (CI) 1.47-2.85, P<0.001, I(2)=85%) compared with non-users. A pooled analysis of three studies showed a significant associated risk of recurrent CDI associated with PPIs, OR 2.51 (95% CI 1.16-5.44, P=0.005, I(2)=78%). Subgroup analysis failed to fully clarify the source of the substantial statistical heterogeneity. Adjusted indirect comparison demonstrated that use of H2RAs as an alternative carried a lower-risk OR 0.71 (95% CI 0.53-0.97) compared with PPIs. Conversely, concomitant use of PPI and antibiotics conferred a greater-risk OR 1.96 (95% CI 1.03-3.70) above that of PPIs alone. For PPI and antibiotics, the Rothman's synergy index was 1.36 and attributable proportion of risk from interaction 0.19, indicating an increased risk from interaction beyond the effects of each drug alone. Despite the substantial statistical and clinical heterogeneity, our findings indicate a probable association between PPI use and incident and recurrent CDI. This risk is further increased by concomitant use of antibiotics and PPI, whereas H2RAs may be less harmful.

DRESS Syndrome Associated with Deferasirox Treatment Recurrent Stress Cardiomyopathy Induced by Over-the-Counter Phenylephrine; Angular Cheilitis after Selective Serotonin Reuptake Inhibitor Treatment; Chemotherapy-Induced Spontaneous Orgasms; Liraglutide-Induced Acute Kidney Injury; Peripheral Edema Associated with Risperidone; Risk of Bleeding with Concurrent Use of Antibiotics and Warfarin

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MEDWATCH program (800-FDA-1088). If you have reported an interesting, preventable ADR to MEDWATCH, please consider sharing the account with our readers. Write to Dr. Shuster at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-947-7797; fax: 215-914-1492; e-mail: joel.shuster@temple.edu ). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MEDWATCH program and Temple University School of Pharmacy. ISMP is an FDA MEDWATCH partner.