Risk of Corneal Graft Rejection and Vaccination: A Matched Case-Control Study From a United States Integrated Health Care System.

PURPOSE: Data on vaccine-associated corneal transplant rejections are limited. We examined the association between graft rejection and vaccination. DESIGN: Matched case-control METHODS: We used electronic health records to identify corneal transplant recipients between January 2008 and August 2022 at Kaiser Permanente Southern California. Cases were transplant recipients who experienced a graft rejection (outcome) during the study period. Randomly selected controls who did not experience a corneal graft rejection at their matched cases' index date (rejection date) were matched in a 3:1 ratio to cases. For controls, index date was determined by adding the number of days between transplant and graft rejection of their matched case to the control's transplant date. RESULTS: The study included 601 cases and 1803 matched controls (mean age 66 years [s.d. 17.0], 52% female, 47% non-Hispanic white). Twenty-three% of cases and 22% of controls received ≥1 vaccinations within 12 weeks prior to the index date. The adjusted odds ratio (aOR) for vaccination in the 12 weeks prior to index date, comparing cases to controls was 1.17 (95% CI: 0.91, 1.50]). The aOR was 1.09 (0.84, 1.43) for 1 vaccination, 1.53 (0.90, 2.61) for 2 vaccinations, and 1.79 (0.55, 5.57) for ≥3 vaccinations. The aOR was 1.60 (0.81, 3.14) for mRNA vaccines, and 1.19 (0.80, 1.78) for adjuvanted/high dose vaccines. CONCLUSIONS: We found no evidence to suggest an association between vaccination and graft rejection. Our findings provide support for the completion of recommended vaccinations for corneal transplant recipients, without significantly increasing the risk of graft rejection.

Treatment of Mycobacterium abscessus Complex.

Of the nontuberculous mycobacteria (NTMs) causing lung disease, members of the Mycobacterium abscessus complex (MABc) present a formidable obstacle to successful management. This challenge starts from a poorly understood pathogenesis, continues with complicated subspecies variation in treatment response, and extends to the multidrug-resistant nature of these organisms. The disease often necessitates the use of intravenous therapy, toxic drug combinations, and, in some cases, lung resection. Like many NTMs, MABc treatment requires prolonged therapy with multiple medications, and pulmonary disease in some subspecies can be impossible to eradicate or cure. This disease also represents a frequent and unique problem in certain populations, including cystic fibrosis and lung transplant recipients, and providers who manage such patients should be familiar with how MABc disease influences management. Because of the rising prevalence of the MABc, especially in patients with complicated underlying pulmonary disease, it is increasingly necessary for infectious diseases and pulmonary medicine clinicians to understand the unique aspects of MABc management and understand when to obtain expert consultation in the care of these patients.

The RESPIRE trials: Two phase III, randomized, multicentre, placebo-controlled trials of Ciprofloxacin Dry Powder for Inhalation (Ciprofloxacin DPI) in non-cystic fibrosis bronchiectasis.

The primary goals of long-term disease management in non-cystic fibrosis bronchiectasis (NCFB) are to reduce the number of exacerbations, and improve quality of life. However, currently no therapies are licensed for this. Ciprofloxacin Dry Powder for Inhalation (Ciprofloxacin DPI) has potential to be the first long-term intermittent therapy approved to reduce exacerbations in NCFB patients. The RESPIRE programme consists of two international phase III prospective, parallel-group, randomized, double-blinded, multicentre, placebo-controlled trials of the same design. Adult patients with idiopathic or post-infectious NCFB, a history of ≥2 exacerbations in the previous 12months, and positive sputum culture for one of seven pre-specified pathogens, undergo stratified randomization 2:1 to receive twice-daily Ciprofloxacin DPI 32.5mg or placebo using a pocket-sized inhaler in one of two regimens: 28days on/off treatment or 14days on/off treatment. The treatment period is 48weeks plus an 8-week follow-up after the last dose. The primary efficacy endpoints are time to first exacerbation after treatment initiation and frequency of exacerbations using a stringent definition of exacerbation. Secondary endpoints, including frequency of events using different exacerbation definitions, microbiology, quality of life and lung function will also be evaluated. The RESPIRE trials will determine the efficacy and safety of Ciprofloxacin DPI. The strict entry criteria and stratified randomization, the inclusion of two treatment regimens and a stringent definition of exacerbation should clarify the patient population best positioned to benefit from long-term inhaled antibiotic therapy. Additionally RESPIRE will increase understanding of NCFB treatment and could lead to an important new therapy for sufferers. TRIAL REGISTRATION: The RESPIRE trials are registered in ClinicalTrials.gov, ID number NCT01764841 (RESPIRE 1; date of registration January 8, 2013) and NCT02106832 (RESPIRE 2; date of registration April 4, 2014).

Pathogens and antibiotic sensitivities in endophthalmitis.

BACKGROUND: Antibiotic prophylaxis in cataract surgery is intended to minimize endophthalmitis. We describe pathogenic organisms, antibiotic sensitivities and antibiotic prophylaxis in culture-proven endophthalmitis cases. DESIGN: Retrospective consecutive case series and community-based setting were used. PARTICIPANTS: Two hundred fifteen cases of endophthalmitis after cataract surgery performed during 2007-2012 in Kaiser Permanente, California. METHODS AND MAIN OUTCOME MEASURES: Descriptive analysis of isolated organisms and antibiotic sensitivities in relation to antibiotic prophylaxis in culture-proven endophthalmitis cases. RESULTS: The majority of culture-confirmed organisms (n = 83) were Gram positive (96%), most notably coagulase-negative Staphylococci (n = 34, 52%), of which all that underwent testing were sensitive to vancomycin (n = 32). Among 19 cases that had received only topical antibiotic prophylaxis, seven (37%) were resistant to the antibiotic given: 50% of cases (5 of 10 isolates) that had received ofloxacin were resistant to this antibiotic, 40% (2 of 5 isolates) that had received gatifloxacin were resistant. In contrast, 100% of cases (n = 4) that had received aminoglycosides were susceptible. Few culture-confirmed cases occurred in patients who received intracameral antibiotic (n = 4). CONCLUSIONS: In cases where fluoroquinolones were administered as antibiotic prophylaxis, isolates demonstrated a degree of bacterial resistance. The majority of endophthalmitis cases isolated occured following topical antibiotic prophylaxis only and were attributed to Gram-positive organisms, while few occurred in association with intracameral antibiotic.

Travel-associated antimicrobial drug-resistant nontyphoidal Salmonellae, 2004-2009.

To evaluate trends in and risk factors for acquisition of antimicrobial-drug resistant nontyphoidal Salmonella infections, we searched Oregon surveillance data for 2004-2009 for all culture-confirmed cases of salmonellosis. We defined clinically important resistance (CIR) as decreased susceptibility to ampicillin, ceftriaxone, ciprofloxacin, gentamicin, or trimethoprim/sulfamethoxazole. Of 2,153 cases, 2,127 (99%) nontyphoidal Salmonella isolates were obtained from a specific source (e.g., feces, urine, blood, or other normally sterile tissue) and had been tested for drug susceptibility. Among these, 347 (16%) isolates had CIR. The odds of acquiring CIR infection significantly increased each year. Hospitalization was more likely for patients with than without CIR infections. Among patients with isolates that had been tested, we analyzed data from 1,813 (84%) who were interviewed. Travel to eastern or Southeast Asia was associated with increased CIR. Isolates associated with outbreaks were less likely to have CIR. Future surveillance activities should evaluate resistance with respect to international travel.

Non-viral opportunistic infections in new users of tumour necrosis factor inhibitor therapy: results of the SAfety Assessment of Biologic ThERapy (SABER) study.

OBJECTIVES: To determine among patients with autoimmune diseases in the USA whether the risk of non-viral opportunistic infections (OI) was increased among new users of tumour necrosis factor α inhibitors (TNFI), when compared to users of non-biological agents used for active disease. METHODS: We identified new users of TNFI among cohorts of rheumatoid arthritis (RA), inflammatory bowel disease and psoriasis-psoriatic arthritis-ankylosing spondylitis patients during 1998-2007 using combined data from Kaiser Permanente Northern California, two pharmaceutical assistance programmes for the elderly, Tennessee Medicaid and US Medicaid/Medicare programmes. We compared incidence of non-viral OI among new TNFI users and patients initiating non-biological disease-modifying antirheumatic drugs (DMARD) overall and within each disease cohort. Cox regression models were used to compare propensity-score and steroid- adjusted OI incidence between new TNFI and non-biological DMARD users. RESULTS: Within a cohort of 33 324 new TNFI users we identified 80 non-viral OI, the most common of which was pneumocystosis (n=16). In the combined cohort, crude rates of non-viral OI among new users of TNFI compared to those initiating non-biological DMARD was 2.7 versus 1.7 per 1000-person-years (aHR 1.6, 95% CI 1.0 to 2.6). Baseline corticosteroid use was associated with non-viral OI (aHR 2.5, 95% CI 1.5 to 4.0). In the RA cohort, rates of non-viral OI among new users of infliximab were higher when compared to patients newly starting non-biological DMARD (aHR 2.6, 95% CI 1.2 to 5.6) or new etanercept users (aHR 2.9, 95% CI 1.5 to 5.4). CONCLUSIONS: In the USA, the rate of non-viral OI was higher among new users of TNFI with autoimmune diseases compared to non-biological DMARD users.

Bedfellows: mycobacteria and rheumatoid arthritis in the era of biologic therapy.

In modern times a relationship between tuberculosis (TB) and rheumatoid arthritis (RA) has been firmly recognized, and is primarily attributable to the immunosuppressive therapies used to treat RA. Whereas TB can complicate the successful management of RA, nontuberculous mycobacteria have now perhaps become as important as (if not more so than) TB in the setting of RA, and can represent an even greater challenge to the rheumatologist wishing to use immunosuppressive therapies. This article reviews our most recent understanding of the epidemiological and clinical aspects of mycobacterial disease as it relates to RA, and the existing and emerging immunosuppressive therapies used to treat this disease.

Decreased postoperative endophthalmitis rate after institution of intracameral antibiotics in a Northern California eye department.

PURPOSE: To evaluate post-cataract-surgery endophthalmitis rates in relation to changing practice patterns in antibiotic administration. SETTING: Kaiser Permanente, Diablo Service Area, California. DESIGN: Ecological time-trend study. METHODS: During 2007 through 2011, 3 time periods were identified based on increasing adoption of intracameral injections after phacoemulsification cataract surgery. In 2007, patients primarily received postoperative antibiotic drops without intracameral injection. During 2008 and 2009, in addition to the surgeons' usual postoperative topical drop regimen, patients received intracameral cefuroxime unless contraindicated by allergy or posterior capsule rupture (PCR). During 2010 and 2011, all patients received an intracameral injection of cefuroxime, moxifloxacin, or vancomycin while topical antibiotics were used according to surgeon preference. The rates of postoperative endophthalmitis during these 3 periods were calculated. Also evaluated separately were consecutive patients without PCR from a subgroup of 3 surgeons who used intracameral injection alone without perioperative topical antibiotics. RESULTS: Nineteen cases of endophthalmitis occurred in 16,264 cataract surgeries. The respective rates per 1000 during the 3 time periods (2007, 2008 and 2009, 2010 and 2011) were as follows: 3.13 (95% confidence interval [CI], 1.43-5.93); 1.43 (95% CI, 0.66-2.72); 0.14 (95% CI, 0-0.78). One case of endophthalmitis was observed in 2038 patients without PCR who received intracameral injection only without topical antibiotics (rate per 1000: 0.49; 95% CI, 0.01-2.73). CONCLUSIONS: The adoption of intracameral antibiotic injection coincided with a decline in the rate of postoperative endophthalmitis, and a low infection rate was observed with intracameral injection alone.

Infections and biologic therapy in rheumatoid arthritis: our changing understanding of risk and prevention.

Patients with rheumatoid arthritis are at higher risk for serious infections and death from infection than the general public. Prednisone and biologic agents increase this risk, although the risk associated with biologics can be mitigated when such agents act as prednisone-sparing therapies. Some of the important causes of infectious morbidity in this setting are preventable with screening (eg, tuberculosis) or vaccination (eg, herpes zoster).

Mycobacterial and other serious infections in patients receiving anti-tumor necrosis factor and other newly approved biologic therapies: case finding through the Emerging Infections Network.

We present the results of a nationwide survey of infectious disease consultants to identify mycobacterial and other serious infections in patients receiving anti-tumor necrosis factor compounds and other novel targeted therapies. Nontuberculous mycobacterial infections, histoplasmosis, and invasive Staphylococcus aureus infection were all reported more frequently than was tuberculosis disease in this context.

Mycobacteria in nail salon whirlpool footbaths, California.

In 2000, an outbreak of Mycobacterium fortuitum furunculosis affected customers using whirlpool footbaths at a nail salon. We swabbed 30 footbaths in 18 nail salons from 5 California counties and found mycobacteria in 29 (97%); M. fortuitum was the most common. Mycobacteria may pose an infectious risk for pedicure customers.

An outbreak of mycobacterial furunculosis associated with footbaths at a nail salon.

BACKGROUND: In September 2000, a physician in northern California described four patients with persistent, culture-negative boils on the lower extremities. The patients had received pedicures at the same nail salon. We identified and investigated an outbreak of Mycobacterium fortuitum furunculosis among customers of this nail salon. METHODS: Patients were defined as salon customers with persistent skin infections below the knee. A case-control study was conducted that included the first 48 patients identified, and 56 unaffected friends and family members who had had a pedicure at the same salon served as controls. Selected M. fortuitum isolates, cultured from patients and the salon environment, were compared by pulsed-field gel electrophoresis. RESULTS: We identified 110 customers of the nail salon who had furunculosis. Cultures from 34 were positive for rapidly growing mycobacteria (32 M. fortuitum and 2 unidentified). Most of the affected patients had more than 1 boil (median, 2; range, 1 to 37). All patients and controls had had whirlpool footbaths. Shaving the legs with a razor before pedicure was a risk factor for infection (70 percent of patients vs. 31 percent of controls; adjusted odds ratio, 4.8; 95 percent confidence interval, 2.1 to 11.1). Cultures from all 10 footbaths at the salon yielded M. fortuitum. The M. fortuitum isolates from three footbaths and 14 patients were indistinguishable by electrophoresis. CONCLUSIONS: We identified a large outbreak of rapidly growing mycobacterial infections among persons who had had footbaths and pedicures at one nail salon. Physicians should suspect this cause in patients with persistent furunculosis after exposure to whirlpool footbaths.