Intravenous administration of Penicillin results in therapeutic intravitreal levels in chronic postoperative endophthalmitis.

IMPORTANCE: The role of systemic antibiotics in the treatment of bacterial endophthalmitis remains controversial. While penicillin is a highly effective antibiotic against bacteria that frequently cause endophthalmitis, the ability of systemically administered Penicillin G to penetrate into the vitreous at adequate therapeutic concentrations has not been studied. Its role in the treatment of endophthalmitis, particularly for bacteria for which it is the antibiotic of choice, therefore remains unknown. OBJECTIVE: We sought to determine whether intravenous administration of Penicillin G leads to adequate therapeutic concentrations in the vitreous for the treatment of bacterial endophthalmitis. DESIGN AND SETTING: This study was conducted in an ambulatory setting, at the Ottawa Hospital Eye Institute, a university-affiliated tertiary care center, where a 77-year old gentleman with chronic post-cataract surgery Actinomyces neuii endophathalmitis was treated with intravenous Penicillin G (4 × 106 units every 4 h) and intravitreal ampicillin (5000µg/0.1 m1). MAIN OUTCOMES AND MEASURES: Intravitreal concentration of Penicillin G and ampicillin were obtained at the time of intraocular lens removal, measured by high-performance liquid chromatography. RESULTS: The intravitreal concentration of penicillin and ampicillin was 3.5µg/ml and 0.3µg/ml, respectively. Both the concentration of penicillin and ampicillin were within the level of detection of their respective assays (penicillin 0.06-5µg/ml, ampicillin 0.12-2.5µg/ml). CONCLUSION AND RELEVANCE: This study shows that intravenous Penicillin G administered every four-hours allows for adequate intravitreal concentrations of penicillin. Future studies are required to determine if the results of this study translate into improved clinical outcomes.

Toxoplasmosis, cryptosporidiosis, and isosporiasis in HIV-negative immunocompromised patients: A single-centre study, Ottawa, Ontario, Canada.

Background: Historically, patients with HIV have been at the highest risk of infection with opportunistic protozoans such as Toxoplasma, Cryptosporidium, and Isospora. Among patients with HIV who are compliant with antiretroviral therapy, the likelihood of acquiring an opportunistic infection is low. The risk of infection is harder to mitigate in the growing number of HIV-negative immunodeficient patients, such as people with hematological malignancies or those who are post-transplantation. Methods: We conducted a retrospective case series of patients with documented Toxoplasma infections between 2008 and 2017 and with Cryptosporidium and Isospora infections between 2014 and 2017 at the Ottawa Hospital. Results: During the study period, there were 10 confirmed cases of toxoplasmosis, 20 cases of cryptosporidiosis, and 2 cases of isosporiasis. Cryptosporidiosis (95%) and toxoplasmosis (60%) occurred more frequently among HIV-negative patients, whereas isosporiasis cases were limited to HIV-positive patients. Among patients with cryptosporidiosis, the most common underlying cause of immunosuppression in HIV-negative individuals was solid organ transplantation (15.79%), followed by diabetes (10.53%), end-stage renal disease (5.26%), and hematologic malignancy (5.26%). Seventy percent of patients had no known cause of immunosuppression. The most common underlying condition associated with toxoplasmosis was hematological malignancy (50%), followed by solid organ transplantation (33.33%), and solid tumours (16.66%). Conclusions: This study's results suggest that Cryptosporidium infections are more common among immunocompetent patients in Ottawa, whereas Toxoplasma infections are more common among HIV-negative patients with acquired immunodeficiencies. As the demographics of immunocompromised individuals continue to evolve, screening for protozoal infections in high-risk populations may become clinically important.

Historique: Par le passé, les patients atteints du VIH présentaient le plus fort risque d'infection par des protozoaires opportunistes comme le Toxoplasma, le Cryptosporidium et l'Isospora. Chez les patients atteints du VIH qui adhèrent à la thérapie antivirale, la probabilité de contracter une infection opportuniste est faible. Le risque d'infection est toutefois plus difficile à contrôler auprès du nombre croissant de patients immunodéprimés non atteints du VIH, tels que ceux qui souffrent d'un cancer hématologique ou qui ont subi une transplantation. Méthodologie: Les chercheurs ont réalisé une étude auprès d'une série de patients rétrospectifs atteints d'une infection démontrée par le Toxoplasma entre 2008 et 2017 ainsi que d'une infection par le Cryptosporidium et l'Isospora entre 2014 et 2017 à l'Hôpital d'Ottawa. Résultats: Pendant la période de l'étude, dix cas confirmés de toxoplasmose, 20 cas de cryptosporidiose et deux cas d'isosporose ont été recensés. La cryptosporidiose (95 %) et la toxoplasmose (60 %) étaient plus fréquentes chez les patients non atteints du VIH, mais les cas d'isosporose étaient limités aux patients atteints du VIH. Chez les patients atteints de la cryptosporidiose, la transplantation d'un organe plein (15,79 %) était la cause principale d'immunodépression chez les patients non atteints du VIH, suivie du diabète (10,53 %), de l'insuffisance rénale terminale (5,26 %) et du cancer hématologique (5,26 %). Toutefois, 70 % des patients ne présentaient aucune cause connue d'immunodépression. Le cancer hématologique (50 %) était l'affection la plus associée à la toxoplasmose, suivi de la transplantation d'un organe plein (33,33 %) et des tumeurs solides (16,66 %). Conclusions: Selon les résultats de la présente étude, les infections à Cryptosporidium sont plus courantes chez les patients immunocompétents d'Ottawa, mais celles à Toxoplasma le sont davantage chez les patients qui ne sont pas atteints du VIH, mais qui ont une immunodéficience acquise. Devant l'évolution de la démographie des patients immunodéprimés, le dépistage des infections protozoaires peut devenir important sur le plan clinique dans les populations à haut risque.

Validation of an Algorithm to Identify Infective Endocarditis in People Who Inject Drugs.

INTRODUCTION: Infective endocarditis is associated with high morbidity and mortality. Currently, there is concern that the incidence of infective endocarditis associated with people who inject drugs (PWID) is increasing. However, it is difficult to monitor population-wide trends in PWID-associated infective endocarditis, as there is no International Statistical Classification of Diseases, 10th Revision (ICD-10) code for injection drug use. To address this barrier, we sought to develop a validated algorithm using ICD-10 discharge diagnosis codes. MATERIALS AND METHODS: We constructed a cohort of patients whose hospital discharge diagnosis included infective endocarditis. We reviewed 100 patients with incident infective endocarditis from 2014 to 2016 for their infective endocarditis and injection drug use status. We calculated the operating characteristics for algorithms constructed using permutations of ICD-10 codes associated with injection drug use. We repeated this analysis in a cohort of 100 patients with incident infective endocarditis from 2009 to 2011 to examine the temporal stability of the operating characteristics of each algorithm. RESULTS: We found that a combination of hepatitis C virus, drug use, and mental/behavioral disorder codes yielded the highest sensitivity (93%) and positive predictive value (83%) of the algorithms analyzed. DISCUSSION: We have described the first algorithm, validated against chart review data, for identifying PWID-associated infective endocarditis cases using ICD-10 codes. The high sensitivity and positive predictive value indicate that this algorithm can be used for surveillance and research with confidence. CONCLUSIONS: This algorithm will enable researchers to examine epidemiological trends in PWID-associated infective endocarditis.

Clinical Characteristics and Factors Associated With Mortality in First-Episode Infective Endocarditis Among Persons Who Inject Drugs.

Importance: Persons who inject drugs (PWID) represent a distinct demographic of patients with infective endocarditis. Many centers do not perform valvular surgery on these patients owing to concerns about poor outcomes. Addiction services are underused in hospitals. Objectives: To compare clinical characteristics in first-episode infective endocarditis in PWID who are surgically vs medically managed and to identify variables associated with mortality. Design, Setting, and Participants: This case series studied PWID treated for a first episode of infective endocarditis between April 1, 2007, and March 30, 2016. Participants were adult patients (aged ≥18 years) admitted to any of 3 hospitals in London, Ontario, Canada. Analysis occurred between July 2016 and November 2017. Main Outcomes and Measures: Survival among PWID; the causative organisms, site of infection, and cardiac as well as noncardiac complications; referral to addiction services; and surgical vs medical management. Results: Of 370 total first-episode cases of infective endocarditis, 202 (54.6%) were in PWID. Among PWID, 105 (52%) were male, the median (interquartile range) age was 34 (28-42) years, and patients were predominantly positive for the hepatitis C virus (69.8% [141 of 202]). Right-sided infection was more common (61.4% [124 of 202]), and most infections were caused by Staphylococcus aureus (77.2% [156 of 202]). Surgery occurred in 19.3% of patients (39 of 202). The all-cause mortality rate was 33.7% (68 of 202). Adjusting for age and sex, survival analysis demonstrated that surgery was associated with lower mortality (hazard ratio [HR], 0.44; 95% CI, 0.23-0.84; P = .01), as was referral to addiction treatment (HR, 0.29; 95% CI, 0.12-0.73; P = .008). Higher mortality was associated with left-sided infection (HR, 3.26; 95% CI, 1.82-5.84; P < .001) and bilateral involvement (HR, 4.51; 95% CI, 2.01-10.1; P < .001). Conclusions and Relevance: This study presents the demographic characteristics of first-episode infective endocarditis in PWID. Results highlight the potentially important role of addictions treatment in this population. Further study to optimize selection criteria for surgery in PWID is warranted.