The Improved Kidney Risk Score in ANCA-Associated Vasculitis for Clinical Practice and Trials.

SIGNIFICANCE STATEMENT: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. More than 1500 patients were collated in an international longitudinal study to revise the ANCA kidney risk score. The score showed satisfactory performance, mimicking the original study (Harrell's C=0.779). In the development cohort of 959 patients, no additional parameters aiding the tool were detected, but replacing the GFR with creatinine identified an additional cutoff. The parameter interstitial fibrosis and tubular atrophy was modified to allow wider access, risk points were reweighted, and a fourth risk group was created, improving predictive ability (C=0.831). In the validation, the new model performed similarly well with excellent calibration and discrimination ( n =480, C=0.821). The revised score optimizes prognostication for clinical practice and trials. BACKGROUND: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. A retrospective international longitudinal cohort was collated to revise the ANCA renal risk score. METHODS: The primary end point was ESKD with patients censored at last follow-up. Cox proportional hazards were used to reweight risk factors. Kaplan-Meier curves, Harrell's C statistic, receiver operating characteristics, and calibration plots were used to assess model performance. RESULTS: Of 1591 patients, 1439 were included in the final analyses, 2:1 randomly allocated per center to development and validation cohorts (52% male, median age 64 years). In the development cohort ( n =959), the ANCA renal risk score was validated and calibrated, and parameters were reinvestigated modifying interstitial fibrosis and tubular atrophy allowing semiquantitative reporting. An additional cutoff for kidney function (K) was identified, and serum creatinine replaced GFR (K0: <250 µ mol/L=0, K1: 250-450 µ mol/L=4, K2: >450 µ mol/L=11 points). The risk points for the percentage of normal glomeruli (N) and interstitial fibrosis and tubular atrophy (T) were reweighted (N0: >25%=0, N1: 10%-25%=4, N2: <10%=7, T0: none/mild or <25%=0, T1: ≥ mild-moderate or ≥25%=3 points), and four risk groups created: low (0-4 points), moderate (5-11), high (12-18), and very high (21). Discrimination was C=0.831, and the 3-year kidney survival was 96%, 79%, 54%, and 19%, respectively. The revised score performed similarly well in the validation cohort with excellent calibration and discrimination ( n =480, C=0.821). CONCLUSIONS: The updated score optimizes clinicopathologic prognostication for clinical practice and trials.

IgA vasculitis nephritis-outcomes in adult-onset disease.

OBJECTIVES: IgA vasculitis (IgAV) in adults has been relatively under-investigated. Since outcomes are worse in other forms of vasculitis with increasing age, we investigated the outcomes of IgAV comparing younger adults (18-34), middle aged adults (35-64) and elderly patients (≥64 years) focusing on kidney outcomes. METHODS: We identified patients with renal biopsy confirmed IgAV nephritis and collected data regarding clinical features and progression to end stage kidney disease (ESKD). The relationship between patient factors and ESKD was analysed by regression. RESULTS: We identified 202 cases, 34% aged 18-34, 43% aged 35-64 and 23% were elderly (>64 years). Median follow up was 44 months. Elderly patients were more likely to present with ESKD (23.9%) compared with middle aged (13.7%) and younger adults (2.9%)(χ2 11.6, p= 0.002). In patients with independent kidney function at biopsy, there was no difference in outcomes between age groups. Male gender, Black ethnicity, diabetes, histological evidence of chronic renal damage and eGFR < 30mls/min were risk factors for development of ESKD. In this observational study 68.3% of patients received glucocorticoids and 56.9% additional immunosuppression. CONCLUSIONS: Elderly patients with IgAV are more likely to have ESKD at presentation, but there is no difference in renal survival between age groups, among those presenting with independent renal function. Renal impairment at biopsy is an independent risk factor for subsequent development of ESKD. There is significant variability in the timing of kidney biopsy and management of these patients among specialist centres. Young adults have outcomes more in keeping with childhood IgAV.

Risk Stratification to Predict Renal Survival in Anti-Glomerular Basement Membrane Disease.

SIGNIFICANCE STATEMENT: Most patients with anti-glomerular basement membrane (GBM) disease present with rapidly progressive glomerulonephritis, and more than half develop ESKD. Currently, no tools are available to aid in the prognostication or management of this rare disease. In one of the largest assembled cohorts of patients with anti-GBM disease (with 174 patients included in the final analysis), the authors demonstrated that the renal risk score for ANCA-associated vasculitis is transferable to anti-GBM disease and the renal histology is strongly predictive of renal survival and recovery. Stratifying patients according to the percentage of normal glomeruli in the kidney biopsy and the need for RRT at the time of diagnosis improves outcome prediction. Such stratification may assist in the management of anti-GBM disease. BACKGROUND: Prospective randomized trials investigating treatments and outcomes in anti-glomerular basement membrane (anti-GBM) disease are sparse, and validated tools to aid prognostication or management are lacking. METHODS: In a retrospective, multicenter, international cohort study, we investigated clinical and histologic parameters predicting kidney outcome and sought to identify patients who benefit from rescue immunosuppressive therapy. We also explored applying the concept of the renal risk score (RRS), currently used to predict renal outcomes in ANCA-associated vasculitis, to anti-GBM disease. RESULTS: The final analysis included 174 patients (out of a total of 191). Using Cox and Kaplan-Meier methods, we found that the RRS was a strong predictor for ESKD. The 36-month renal survival was 100%, 62.4%, and 20.7% in the low-risk, moderate-risk, and high-risk groups, respectively. The need for renal replacement therapy (RRT) at diagnosis and the percentage of normal glomeruli in the biopsy were independent predictors of ESKD. The best predictor for renal recovery was the percentage of normal glomeruli, with a cut point of 10% normal glomeruli providing good stratification. A model with the predictors RRT and normal glomeruli ( N ) achieved superior discrimination for significant differences in renal survival. Dividing patients into four risk groups led to a 36-month renal survival of 96.4% (no RRT, N ≥10%), 74.0% (no RRT, N <10%), 42.3% (RRT, N ≥10%), and 14.1% (RRT, N <10%), respectively. CONCLUSIONS: These findings demonstrate that the RRS concept is transferrable to anti-GBM disease. Stratifying patients according to the need for RRT at diagnosis and renal histology improves prediction, highlighting the importance of normal glomeruli. Such stratification may assist in the management of anti-GBM disease. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_02_27_JASN0000000000000060.mp3.

Cervical screening uptake and rates of cervical dysplasia in the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

OBJECTIVES: To compare cervical screening attendance and cytology (high- and low-grade cervical dysplasia [HGCD and LGCD]) between women with RA and the English general population and between biologic DMARD (bDMARD)-naïve and exposed women. METHODS: The British Society for Rheumatology Biologics Register for RA (BSRBR-RA), a national prospective study of RA treatment outcomes, was linked to the National Health Service Cervical Screening Programme, providing data for 12 785 women to compare with national screening data. Rates of HGCD/LGCD were compared with rates of negative smears using risk difference calculations between BSRBR-RA and national statistics. Within the BSRBR-RA, coverage was compared between those with low and high physical disability scores, while coverage and cytology results were compared between bDMARD-naïve and -exposed RA patients. RESULTS: The mean 5 year screening coverage was significantly higher in BSRBR-RA (83%) compared with the general population (79%), but lower in women with high disability (78%) compared with lesser disability (85%). Risk differences for HGCD were lower in the BSRBR-RA compared with national statistics, whereas risk differences for LGCD were higher. There was no statistically significant difference in the rates of HGCD or LGCD between bDMARD-exposed and -naïve women. CONCLUSION: This first-ever British analysis of cervical screening rates in RA has shown that women with RA have higher screening rates than the general population. Disability negatively impacts attendance, but treatment type does not. Women with RA did not have an increased risk of HGCD compared with national statistics, which was also not influenced by bDMARD exposure.

Safely reducing haemodialysis frequency during the COVID-19 pandemic.

BACKGROUND: Patients undergoing haemodialysis (HD) are at higher risk of developing worse outcomes if they contract COVID-19. In our renal service we reduced HD frequency from thrice to twice-weekly in selected patients with the primary aim of reducing COVID 19 exposure and transmission between HD patients. METHODS: Dialysis unit nephrologists identified 166 suitable patients (38.4% of our HD population) to temporarily convert to twice-weekly haemodialysis immediately prior to the peak of the COVID-19 pandemic in our area. Changes in pre-dialysis weight, systolic blood pressure (SBP) and biochemistry were recorded weekly throughout the 4-week project. Hyperkalaemic patients (serum potassium > 6.0 mmol/L) were treated with a potassium binder, sodium bicarbonate and received responsive dietary advice. RESULTS: There were 12 deaths (5 due to COVID-19) in the HD population, 6 of which were in the twice weekly HD group; no deaths were definitively associated with change of dialysis protocol. A further 19 patients were either hospitalised and/or developed COVID-19 and thus transferred back to thrice weekly dialysis as per protocol. 113 (68.1%) were still receiving twice-weekly HD by the end of the 4-week project. Indications for transfer back to thrice weekly were; fluid overload (19), persistent hyperkalaemia (4), patient request (4) and compliance (1). There were statistically significant increases in SBP and pre-dialysis potassium during the project. CONCLUSIONS: Short term conversion of a large but selected HD population to twice-weekly dialysis sessions was possible and safe. This approach could help mitigate COVID-19 transmission amongst dialysis patients in centres with similar organisational pressures.

Local Melting Attracts Grain Boundaries in Colloidal Polycrystals.

We find that laser-induced local melting attracts and deforms grain boundaries in 2D colloidal crystals. When a melted region in contact with the edge of a crystal grain recrystallizes, it deforms the grain boundary-this attraction is driven by the multiplicity of deformed grain boundary configurations. Furthermore, the attraction provides a method to fabricate artificial colloidal crystal grains of arbitrary shape, enabling new experimental studies of grain boundary dynamics and ultimately hinting at a novel approach for fabricating materials with designer microstructures.

Successful outcome of pregnancy in patients with anti-neutrophil cytoplasm antibody-associated small vessel vasculitis.

Pregnancy in patients with anti-neutrophil cytoplasm antibody-associated vasculitis is reportedly associated with a high risk of fetal and maternal complications. Here we describe the outcome of pregnancies in patients with granulomatosis with polyangiitis and microscopic polyangiitis at five centers in the United Kingdom using a retrospective case review of all women who became pregnant following diagnosis. We report 15 pregnancies in 13 women resulting in 15 live births including one twin pregnancy and 13 singleton pregnancies. One patient had an unplanned pregnancy and a first trimester miscarriage while taking methotrexate. All other pregnancies were planned following a minimum of 6 months clinical remission. Eleven successful pregnancies were delivered vaginally at full term, whereas three were delivered by cesarean section. All infants were healthy with no neonatal complications on their initial health check within the first 24 h of delivery and no evidence of neonatal vasculitis. One relapse occurred during pregnancy and was successfully treated with an increased dose of azathioprine and corticosteroids, intravenous immunoglobulin, and plasma exchange therapy. One patient developed tracheal crusting and subglottic stenosis of infective etiology in the third trimester requiring tracheal debridement post delivery. No patient had a relapse in the first 12 months postpartum. Thus, successful pregnancy outcomes can occur following planned pregnancy in women in sustained remission on non-teratogenic therapies.

Active learning using adaptable task-based prioritisation.

Supervised machine learning-based medical image computing applications necessitate expert label curation, while unlabelled image data might be relatively abundant. Active learning methods aim to prioritise a subset of available image data for expert annotation, for label-efficient model training. We develop a controller neural network that measures priority of images in a sequence of batches, as in batch-mode active learning, for multi-class segmentation tasks. The controller is optimised by rewarding positive task-specific performance gain, within a Markov decision process (MDP) environment that also optimises the task predictor. In this work, the task predictor is a segmentation network. A meta-reinforcement learning algorithm is proposed with multiple MDPs, such that the pre-trained controller can be adapted to a new MDP that contains data from different institutes and/or requires segmentation of different organs or structures within the abdomen. We present experimental results using multiple CT datasets from more than one thousand patients, with segmentation tasks of nine different abdominal organs, to demonstrate the efficacy of the learnt prioritisation controller function and its cross-institute and cross-organ adaptability. We show that the proposed adaptable prioritisation metric yields converging segmentation accuracy for a new kidney segmentation task, unseen in training, using between approximately 40% to 60% of labels otherwise required with other heuristic or random prioritisation metrics. For clinical datasets of limited size, the proposed adaptable prioritisation offers a performance improvement of 22.6% and 10.2% in Dice score, for tasks of kidney and liver vessel segmentation, respectively, compared to random prioritisation and alternative active sampling strategies.

Innovative Hospital-Based Pediatric Virtual Learning for Nursing Students.

BACKGROUND/PROBLEM: Specialty clinical sites, including pediatrics, are historically scarce in prelicensure nursing education. APPROACH: Simulation educators developed the Pediatric Virtual Clinical Learning Series (PVCLS) containing 4 virtual learning modules designed to enhance knowledge and skills of prelicensure nursing students in clinical pediatric care. Topics included documentation, rapid response, code blue, and a pediatric case. The learning sessions were initially offered as synchronous virtual classes and were then posted on our e-learning platform to serve as enduring asynchronous material. The target audience was nursing students and faculty from regional and nationally affiliated nursing schools with the pediatric hospital. OUTCOMES: Faculty and 185 nursing students participated in the synchronous or asynchronous learning sessions. Students' ratings that the virtual classes met their personal expectations were 4.02 to 4.56 of 5 for the synchronous sessions and 3.41 to 3.58 of 4 for the asynchronous sessions. CONCLUSIONS: The PVCLS provided both synchronous and asynchronous learning experiences to fill a widening knowledge gap in pediatrics.

Naloxone's dose-dependent displacement of [11C]carfentanil and duration of receptor occupancy in the rat brain.

The continuous rise in opioid overdoses in the United States is predominantly driven by very potent synthetic opioids, mostly fentanyl and its derivatives (fentanyls). Although naloxone (NLX) has been shown to effectively reverse overdoses by conventional opioids, there may be a need for higher or repeated doses of NLX to revert overdoses from highly potent fentanyls. Here, we used positron emission tomography (PET) to assess NLX's dose-dependence on both its rate of displacement of [11C]carfentanil ([11C]CFN) binding and its duration of mu opioid receptor (MOR) occupancy in the male rat brain. We showed that clinically relevant doses of intravenously (IV) administered NLX (0.035 mg/kg, Human Equivalent Dose (HED) 0.4 mg; 0.17 mg/kg, HED 2 mg) rapidly displaced the specific binding of [11C]CFN in the thalamus in a dose-dependent manner. Brain MOR occupancy by IV NLX was greater than 90% at 5 min after NLX administration for both doses, but at 27.3 min after 0.035 mg/kg dose and at 85 min after 0.17 mg/kg NLX, only 50% occupancy remained. This indicates that the duration of NLX occupancy at MORs is short-lived. Overall, these results show that clinically relevant doses of IV NLX can promptly displace fentanyls at brain MORs, but repeated or higher NLX doses may be required to prevent re-narcotization following overdoses with long-acting fentanyls.

Deep hashing for global registration of untracked 2D laparoscopic ultrasound to CT.

PURPOSE: The registration of Laparoscopic Ultrasound (LUS) to CT can enhance the safety of laparoscopic liver surgery by providing the surgeon with awareness on the relative positioning between critical vessels and a tumour. In an effort to provide a translatable solution for this poorly constrained problem, Content-based Image Retrieval (CBIR) based on vessel information has been suggested as a method for obtaining a global coarse registration without using tracking information. However, the performance of these frameworks is limited by the use of non-generalisable handcrafted vessel features. METHODS: We propose the use of a Deep Hashing (DH) network to directly convert vessel images from both LUS and CT into fixed size hash codes. During training, these codes are learnt from a patient-specific CT scan by supplying the network with triplets of vessel images which include both a registered and a mis-registered pair. Once hash codes have been learnt, they can be used to perform registration with CBIR methods. RESULTS: We test a CBIR pipeline on 11 sequences of untracked LUS distributed across 5 clinical cases. Compared to a handcrafted feature approach, our model improves the registration success rate significantly from 48% to 61%, considering a 20 mm error as the threshold for a successful coarse registration. CONCLUSIONS: We present the first DH framework for interventional multi-modal registration tasks. The presented approach is easily generalisable to other registration problems, does not require annotated data for training, and may promote the translation of these techniques.

Racial disparities in tissue plasminogen activator treatment rate for stroke: a population-based study.

BACKGROUND AND PURPOSE: Some prior studies have shown that racial disparities exist in intravenous tissue plasminogen activator (tPA) use for acute ischemic stroke. We sought to determine whether race was associated with tPA treatment for stroke in a predominantly black urban population. METHODS: Systematic chart abstraction was performed on consecutive hospitalized patients with ischemic stroke from all 7 acute care hospitals in the District of Columbia from February 1, 2008, to January 31, 2009. RESULTS: Of 1044 patients with ischemic stroke, 74% were black, 19% non-Hispanic white, and 5% received intravenous tPA. Blacks were one third less likely than whites to receive intravenous tPA (3% versus 10%, P<0.001). However, blacks were also less likely than whites to present within 3 hours of symptom onset (13% versus 21%, P=0.004) and also less likely to be tPA-eligible (5% versus 13%, P<0.001). Of those who presented within 3 hours, blacks were almost half as likely to be treated with intravenous tPA than whites (27% versus 46%, P=0.023). The treatment rate for tPA-eligible patients was similar for blacks and whites (70% versus 76%, P=0.62). CONCLUSIONS: In this predominantly black urban population hospitalized for acute ischemic stroke, blacks were significantly less likely to be treated with intravenous tPA due to contraindications to treatment, delayed presentation, and stroke severity. Effective interventions designed to increase treatment in this population need to focus on culturally relevant education programs designed to address barriers specific to this population.

Understanding reasons for delay in seeking acute stroke care in an underserved urban population.

BACKGROUND AND PURPOSE: Few patients arrive early enough at hospitals to be eligible for emergent stroke treatment. There may be barriers specific to underserved, urban populations that need to be identified before effective educational interventions to reduce delay times can be developed. METHODS: A survey of respondents' likely action in a hypothetical stroke situation was given to 253 community volunteers in the catchment areas of a large urban community hospital. Concurrently, 100 structured interviews were conducted in the same hospital with patients with acute stroke or a proxy. RESULTS: In this predominantly urban, black population, if faced with a hypothetical stroke, 89% of community volunteers surveyed said they would call 911 first, and few felt any of the suggested potential barriers applied to them. However, only 12% of patients with stroke interviewed actually called 911 first (OR, 63.9; 95% CI, 29.5 to 138.2). Instead, 75% called a relative/friend. Eighty-nine percent of patients with stroke reported significant delay in seeking medical attention, and almost half said the reason for the delay was thinking the symptoms were not serious and/or they would self-resolve. For those arriving by ambulance, only 25% did so because they thought it would be faster, whereas 35% cited having no other transportation options. CONCLUSIONS: In this predominantly black urban population, although 89% of community volunteers report the intent of calling 911 during a stroke, only 12% of actual patients with stroke did so. Further research is needed to determine and conquer the barriers between behavioral intent and actual behavior to call 911 for witnessed stroke.

Vessel segmentation for automatic registration of untracked laparoscopic ultrasound to CT of the liver.

PURPOSE: Registration of Laparoscopic Ultrasound (LUS) to a pre-operative scan such as Computed Tomography (CT) using blood vessel information has been proposed as a method to enable image-guidance for laparoscopic liver resection. Currently, there are solutions for this problem that can potentially enable clinical translation by bypassing the need for a manual initialisation and tracking information. However, no reliable framework for the segmentation of vessels in 2D untracked LUS images has been presented. METHODS: We propose the use of 2D UNet for the segmentation of liver vessels in 2D LUS images. We integrate these results in a previously developed registration method, and show the feasibility of a fully automatic initialisation to the LUS to CT registration problem without a tracking device. RESULTS: We validate our segmentation using LUS data from 6 patients. We test multiple models by placing patient datasets into different combinations of training, testing and hold-out, and obtain mean Dice scores ranging from 0.543 to 0.706. Using these segmentations, we obtain registration accuracies between 6.3 and 16.6 mm in 50% of cases. CONCLUSIONS: We demonstrate the first instance of deep learning (DL) for the segmentation of liver vessels in LUS. Our results show the feasibility of UNet in detecting multiple vessel instances in 2D LUS images, and potentially automating a LUS to CT registration pipeline.

Grain splitting is a mechanism for grain coarsening in colloidal polycrystals.

In established theories of grain coarsening, grains disappear either by shrinking or by rotating as a rigid object to coalesce with an adjacent grain. Here we report a third mechanism for grain coarsening, in which a grain splits apart into two regions that rotate in opposite directions to match two adjacent grains' orientations. We experimentally observe both conventional grain rotation and grain splitting in two-dimensional colloidal polycrystals. We find that grain splitting occurs via independently rotating "granules" whose shapes are determined by the underlying triangular lattices of the two merging crystal grains. These granules are so small that existing continuum theories of grain boundary energy are inapplicable, so we introduce a hard sphere model for the free energy of a colloidal polycrystal. We find that, during splitting, the system overcomes a free energy barrier before ultimately reaching a lower free energy when splitting is complete. Using simulated splitting events and a simple scaling prediction, we find that the barrier to grain splitting decreases as grain size decreases. Consequently, grain splitting is likely to play an important role in polycrystals with small grains. This discovery suggests that mesoscale models of grain coarsening may offer better predictions in the nanocrystalline regime by including grain splitting.

Use of Virtual Reality for Pediatric Cardiac Critical Care Simulation.

Simulation is a key component of training in the pediatric cardiac intensive care unit (CICU), a complex environment that lends itself to virtual reality (VR)-based simulations. However, VR has not been previously described for this purpose. Two simulations were developed to test the use of VR in simulating pediatric CICU clinical scenarios, one simulating junctional ectopic tachycardia and low cardiac output syndrome, and the other simulating acute respiratory failure in a patient with suspected coronavirus disease 2019. Six attending pediatric cardiac critical care physicians were recruited to participate in the simulations as a pilot test of VR's feasibility for educational and practice improvement efforts in this highly specialized clinical environment. All participants successfully navigated the VR environment and met the critical endpoints of the two clinical scenarios. Qualitative feedback was overall positive with some specific critiques regarding limited realism in some mechanical aspects of the simulation. This is the first described use of VR in pediatric cardiac critical care simulation.

Perspectives from Transgender and Gender Diverse People on How to Ask About Gender.

Purpose: When inquiring about the gender of research participants, most studies use self-generated questions about gender or questions prepared by researchers that have been evaluated for comprehension by transgender and gender diverse (TGD) and cisgender individuals. However, many gaps still exist in this area, including identifying how TGD people would like to see their gender represented in questions about gender identity. To address this issue, we explored the perspectives of TGD people regarding the construction of questions about gender. Methods: In this online study of 695 TGD people (Mage = 25.52), participants provided written suggestions for how to ask about gender and these responses were analyzed thematically. Data were collected between fall 2015 and summer 2017. Results: Three broad categories of responses emerged: (1) specific identities to include in response options; (2) specific questions to ask about gender; and (3) qualifiers/nuanced considerations. Conclusion: Participants provided a variety of suggestions for how to ask about gender and future research is needed to explore the implementation of these suggestions. Recommendations are provided for options that researchers can explore for how to ask about gender. These findings highlight the ways that TGD people would like their gender to be asked about, which is necessary information to ensure that questions about gender reflect TGD people's identities accurately.

In vitro activity of doripenem, a carbapenem for the treatment of challenging infections caused by gram-negative bacteria, against recent clinical isolates from the United States.

Doripenem, a 1beta-methylcarbapenem, is a broad-spectrum antibiotic approved for the treatment of complicated urinary tract and complicated intra-abdominal infections. An indication for hospital-acquired pneumonia including ventilator-associated pneumonia is pending. The current study examined the activity of doripenem against recent clinical isolates for the purposes of its ongoing clinical development and future longitudinal analysis. Doripenem and comparators were tested against 12,581 U.S. clinical isolates collected between 2005 and 2006 including isolates of Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus pneumoniae, Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter spp. MICs (microg/ml) were established by broth microdilution. By MIC(90), doripenem was comparable to imipenem and meropenem in activity against S. aureus (methicillin susceptible, 0.06; resistant, 8) and S. pneumoniae (penicillin susceptible, < or =0.015; resistant, 1). Against ceftazidime-susceptible Enterobacteriaceae, the MIC(90) of doripenem (0.12) was comparable to that of meropenem (0.12) and superior to that of imipenem (2), though susceptibility of isolates exceeded 99% for all evaluated carbapenems. The activity of doripenem was not notably altered against ceftazidime-nonsusceptible or extended-spectrum beta-lactamase screen-positive Enterobacteriaceae. Doripenem was the most potent carbapenem tested against P. aeruginosa (MIC(90)/% susceptibility [%S]: ceftazidime susceptible = 2/92%S, nonsusceptible = 16/61%S; imipenem susceptible = 1/98.5%S, nonsusceptible = 8/56%S). Against imipenem-susceptible Acinetobacter spp., doripenem (MIC(90) = 2, 89.1%S) was twice as active by MIC(90) as were imipenem and meropenem. Overall, doripenem potency was comparable to those of meropenem and imipenem against gram-positive cocci and doripenem was equal or superior in activity to meropenem and imipenem against Enterobacteriaceae, including beta-lactam-nonsusceptible isolates. Doripenem was the most active carbapenem tested against P. aeruginosa regardless of beta-lactam resistance.

Increasing prevalence of methicillin resistance in serious ocular infections caused by Staphylococcus aureus in the United States: 2000 to 2005.

PURPOSE: To report the nationwide prevalence of methicillin resistance in serious ocular infections involving Staphylococcus aureus and profile in vitro antimicrobial susceptibility of S aureus from ocular isolates over time. SETTING: Mount Sinai School of Medicine, New York, New York, USA. METHODS: Data on S aureus submitted to The Surveillance Network (TSN) by more than 200 laboratories in the United States from January 2000 to December 2005 were reviewed. The prevalence of methicillin resistance in S aureus ocular infections and in vitro susceptibility to antibiotic agents commonly used to treat or prevent ocular infections were determined. RESULTS: The proportion of S aureus infections culture-positive for methicillin-resistant S aureus (MRSA) increased from 29.5% in 2000 to 41.6% in 2005. The MRSA ocular isolates were multidrug resistant; that is, in vitro resistance to 3 antibiotic agents or more, including all fluoroquinolones tested. CONCLUSIONS: Multidrug-resistant MRSA is increasing in serious ocular infections. Based on the rate of increase in the TSN database, MRSA cultures from serious ocular infections could be more common than methicillin-susceptible S aureus within 2 to 3 years. Large-scale national surveillance programs are needed to monitor in vitro antimicrobial resistance trends in ocular isolates.