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BackgroundNovel combination therapies to overcome anti-PD-1 resistance are required. Enadenotucirev, a tumor-selective blood stable adenoviral vector, has demonstrated a manageable safety profile and ability to increase tumor immune-cell infiltration in phase I studies in solid tumors.MethodsWe conducted a phase I multicenter study of intravenous enadenotucirev plus nivolumab in patients with advanced/metastatic epithelial cancer not responding to standard therapy. Co-primary objectives were safety/tolerability and maximum tolerated dose and/or maximum feasible dose (MTD/MFD) of enadenotucirev plus nivolumab. Additional endpoints included response rate, cytokine responses, and anti-tumor immune responses.ResultsOverall, 51 heavily pre-treated patients were treated, 45/51 (88%) of whom had colorectal cancer (35/35 patients with information available were microsatellite instability-low/microsatellite stable) and 6/51 (12%) had squamous cell carcinoma of the head and neck. The MTD/MFD of enadenotucirev plus nivolumab was not reached, with the highest dose level tested (1×1012 vp day 1; 6×1012 vp days 3 and 5) shown to be tolerable. Overall, 31/51 (61%) patients experienced a grade 3–4 treatment-emergent adverse event (TEAE), most frequently anemia (12%), infusion-related reaction (8%), hyponatremia (6%), and large intestinal obstruction (6%). Seven (14%) patients experienced serious TEAEs related to enadenotucirev; the only serious TEAE related to enadenotucirev occurring in >1 patient was infusion-related reaction (n=2). Among the 47 patients included in efficacy analyses, median progression-free survival was 1.6 months, objective response rate was 2% (one partial response for 10 months), and 45% of patients achieved stable disease. Median overall survival was 16.0 months; 69% of patients were alive at 12 months. Persistent increases in Th1 and related cytokines (IFNγ, IL-12p70, IL-17A) were seen from ~day 15 in two patients, one of whom had a partial response. Among the 14 patients with matching pre-tumor and post-tumor biopsies, 12 had an increase in intra-tumoral CD8+T-cell infiltration and 7 had increased markers of CD8 T-cell cytolytic activity.ConclusionsIntravenously dosed enadenotucirev plus nivolumab demonstrated manageable tolerability, an encouraging overall survival and induced immune cell infiltration and activation in patients with advanced/metastatic epithelial cancer. Studies of next-generation variants of enadenotucirev (T-SIGn vectors) designed to further re-program the tumor microenvironment by expressing immune-enhancer transgenes are ongoing.Trial registration numberNCT02636036.

Delivery of dialysis through a tunnelled central venous access device (CVAD) is associated with a high risk of infection, when compared with other routes. The risk of contamination increases when the catheter dressing becomes wet, for example, when the patient is showering. Entry of the bacteria into the blood stream can result in a systemic infection. Protection pouches can be used to avoid this risk

BackgroundMicrosatellite-stable (MSS) and instability-low (MSI-L) metastatic colorectal cancer (mCRC) are typically characterised as ”immune-excluded/desert” tumour microenvironments lacking T-cell infiltration. Anti-PD-1 monotherapy has little clinical benefit in MSS/MSI-L mCRC1 and knowledge of the effects of PD-1 inhibition on T-cell activation/infiltration in this population is limited. Novel combination therapies to overcome anti-PD-1 resistance are required. SPICE is a multicentre, open-label, phase 1 study of the tumour-selective chimeric Ad11/Ad3 group B oncolytic adenovirus enadenotucirev plus nivolumab in patients with metastatic/advanced epithelial tumours refractory to standard therapy. Preliminary data from patients with MSS/MSI-L mCRC demonstrated a median overall survival of 14 months, manageable tolerability and intratumoural T-cell infiltration.2 Here we characterise the immunological effects of tumour re-engineering with enadenotucirev in combination with nivolumab in patients with MSS/MSI-L mCRC.MethodsPatients received increasing doses and/or cycles of intravenous enadenotucirev followed by up to 8 cycles of nivolumab as previously described.2 Wherever possible, pre- and post-treatment (~5 weeks post-first enadenotucirev) biopsies were collected; samples were analysed using immunohistochemistry and automated image analysis. Peripheral blood mononuclear cell immunophenotyping (multiparameter flow cytometry) and serum cytokines were assessed at multiple times.Results43 patients with mCRC were treated (86% MSS/MSI-L; 14% unknown). Among the 13 patients (12/13 MSS/MSI-L; 1/13 unknown) with matched biopsies, 11 had increased intratumoural and stromal CD8+ T-cell infiltration in post-treatment biopsies (median [Q1-Q3] fold changes 6.5× [1.5–25.4] and 1.9× [1.5–3.9], respectively; figure 1). CD4+ T-cell density increased in 10/13 patients and 8/13 patients had increased proportions of PD-L1+ immune cells. Increases in CD8 T-cell proliferation (Ki67; 7/9 patients) and cytolytic activity (Granzyme B; 7/13 patients) markers were seen. 4/13 patients converted from a ”desert” to an ”inflamed” immune phenotype (pathologist scored CD8/pan-cytokeratin staining). Immunophenotyping showed trends towards increased T-cell activation (CD38+ and HLA-DR+ CD8+ T cell populations) post-treatment (9/10 patients), including in one patient who had only received enadenotucirev prior to sampling. Persistent increases in inflammatory cytokines (IFNγ, IL-12p70, IL-17a) were seen in two patients from ~Day 15, including one who achieved a sustained objective response.Abstract 342 Figure 1Tumour immune cell infiltration following treatment with enadenotucirev plus nivolumabConclusionsThese data show that intravenous enadenotucirev plus nivolumab can induce immune infiltration/activation within MSS/MSI-L mCRC. These encouraging findings suggest that immune activation can be achieved even in ”immune-excluded/desert” tumours. SPICE has been closed following completion of dose-escalation. Efforts are now focused on the development of next-generation variants of enadenotucirev designed to further re-programme the tumour microenvironment by expressing immune-enhancer transgenes (T-SIGn vectors); these studies are ongoing (NCT04830592, NCT04053283, NCT03852511).AcknowledgementsThis study was funded by PsiOxus Therapeutics Limited and Bristol Myers Squibb. Medical writing support: Lola Parfitt, MRes, of PsiOxus Therapeutics Limited.Trial RegistrationEudraCT number2017-001231-39NCT number: NCT02636036ReferencesKawazoe A, Kuboki Y, Shinozaki E, et al. Multicenter phase I/II trial of napabucasin and pembrolizumab in patients with metastatic colorectal cancer (EPOC1503/SCOOP trial). Clin Cancer Res 2020;26:5887–5894.Fakih M, Wang D, Harb W, et al. SPICE: a phase I multicenter study of enadenotucirev in combination with nivolumab in tumors of epithelial origin: an analysis of the metastatic colorectal cancer patients in the dose escalation phase. Ann Oncol 2019:30(suppl_5):v252.Ethics ApprovalThe study was approved by the WCG Institutional Review Board (study approval number 20152656), UCLA Institutional Review Board (study approval number IRB#15-002010), Vanderbilt Institutional Review Board (study approval number IRB #171453) and Henry Ford Institutional Review Board (study approval number IRB #10349).

Background: The efficacy of immune checkpoint inhibitors is often limited by immunosuppressive tumor microenvironments (TME) and novel combination therapies are required to overcome resistance. NG-350A is a novel T-SIGn (Tumor-Specific Immuno Gene) adenoviral vector that expresses a fully human agonistic IgG anti-CD40 antibody to promote innate and adaptive immune responses. Additionally, NG-350A selectively replicates in tumor cells, allowing IV dosing to be coupled with local transgene expression in the TME, thereby targeting all tumor lesions while limiting systemic exposure. Through these immunostimulatory effects the vector is designed to re-program ‘cold’ TMEs to allow functional anti-cancer immune responses. Data from an ongoing study with IV NG-350A monotherapy have shown promising tolerability, as well as prominent and sustained elevations in inflammatory cytokines (IL-2, IFNγ, IL-17A, IL-2 and IFNα2) consistent with the mechanism of action of anti-CD40 in stimulating TME re-programming [Naing 2021]. Based on these promising initial data, we designed a study to further assess the safety, tolerability and preliminary efficacy of NG-350A + pembrolizumab. Methods: FORTIFY (NCT05165433) is an open-label, dose-escalating, phase 1a/b study of NG-350A + pembrolizumab. Eligible patients have advanced/metastatic epithelial tumors that have progressed after ≥1 line of systemic therapy and are incurable by local therapy. Patients eligible for phase 1a must have experienced failure of prior PD-1/PD-L1 inhibition as part of any prior line of therapy; patients eligible for phase 1b must have primary resistance to PD-1/PD-L1 inhibition. During phase 1a, up to 30 patients will receive escalating doses of IV NG-350A (Bayesian Optimal Interval design) to a maximum of 1 × 1012 viral particles (vp) on Day 1 and 1 × 1013 vp on Days 3 and 5 (1 cycle). Patients will receive a fixed-dose of pembrolizumab (200 mg IV) on Day 15 and then every 3 weeks thereafter for up to 35 cycles. Phase 1b will further investigate the efficacy/safety of the selected regimen in up to 3 tumor-specific cohorts using a Simon 2-stage design. Co-primary objectives are to characterize the safety and tolerability of NG-350A + pembrolizumab and to identify a recommended dose. Preliminary efficacy and immunogenicity are secondary endpoints. Pharmacodynamic outcomes will be assessed using tumor tissues and blood. Analyses of tumor tissue (serial biopsies at baseline and Day 15 of cycles 1-3 [cycles 1-2 only in Phase 1b]) will explore virus replication, transgene expression and immune/inflammatory responses. Analyses of serial blood samples will explore cytokine production and changes in peripheral immune cell subsets. Recruitment is expected to begin in Q1 2022. Citation Format: Tom Lillie, Mark O'Hara, Christian Ottensmeier, Eileen Parkes, Lee Rosen, David Krige, Marya Chaney, Jo Carter, Vladimir Evilevitch, Matthew Thomas, Aung Naing. A multicenter phase 1a/b study of NG-350A, a tumor-selective anti-CD40-antibody expressing adenoviral vector, and pembrolizumab in patients with metastatic or advanced epithelial tumors (FORTIFY) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT213.

2559 Background: Stimulating CD40 may support anti-cancer immune responses; however, on-target toxicity limits systemic dosing. NG-350A is a tumor-selective and blood stable adenoviral T-SIGn vector expressing a potent fully human IgG agonistic anti-CD40 antibody (mAb). NG-350A was designed to selectively deliver anti-CD40 to multiple tumor sites via IV delivery, driving immunological tumor re-engineering while avoiding systemic toxicity. We report results from a first-in-human trial after completion of enrollment. Methods: FORTITUDE (NCT03852511) is a phase 1 study of NG-350A ± pembro in patients (pts) with metastatic/advanced epithelial tumors. NG-350A monotherapy (mTx) was dose-escalated in separate intratumoral (IT; increasing numbers of doses) or IV (one cycle; three increasing dose levels) cohorts. IV NG-350A + pembro (200 mg Q3W for ≤8 cycles) was then assessed. Results: As of Jan 2022, 28 heavily pre-treated pts had received NG-350A, either as IT mTx (n=9; two dose levels), IV mTx (n=16; IV dose levels 1, 3 & 4) or IV + pembro (n=3; IV dose level 2). The MTD of NG-350A ± pembro was not reached, with no DLTs at the highest IT and IV dose levels. The safety profile of NG-350A was consistent with acute reactions to viral particles and asymptomatic aPTT prolongations (Table). No systemic CD40 transgene protein was detected at any dose level and the only SAE to occur in >1 pt was pneumonia. No objective responses were observed; however, 3/6 patients treated with NG-350A mTx at IV dose level 4 achieved stable disease (dose not yet tested with pembro). Dose-dependent specific increases in serum IL-12, IFNγ and IL-17a were detected in pts treated with IV NG-350A mTx from ̃Wk 2. Increases were sustained at ≥5x baseline levels 7 wks after dosing in the majority of evaluable pts treated at higher IV dose levels. These responses did not occur with IT dosing (or in prior studies with an unarmed vector); further follow-up is ongoing for NG-350A + pembro. IV NG-350A also led to the expansion of T cell clones in blood; most of these were newly detected. Conclusions: NG-350A ± pembro was well-tolerated, with no evidence of CD40-related toxicity. NG-350A IV mTx led to specific and sustained cytokine responses consistent with the MoA of the encoded anti-CD40 Ab. Peak cytokine elevations were typically higher than reported with systemic anti-CD40 Abs, suggesting NG-350A can drive local immunological tumor changes while avoiding systemic toxicity. A further trial (FORTIFY, NCT05165433) will continue dose-escalation of NG-350A + pembro to identify a dose level for efficacy assessments. Clinical trial information: NCT03852511. [Table: see text]

2572 Background: Tumor-selective viruses, particularly those dosed systemically to deliver transgenes, are potentially powerful cancer therapies. However, acute cytokine reactions to viral particle (vp) infusion may affect vector tolerability [Small 2006], thereby limiting the maximum tolerated dose (MTD) and subsequent transgene delivery. T-SIGn vectors (e.g. NG-641 and NG-350A) are transgene-armed variants of the epithelial tumor-selective adenovirus enadenotucirev (EnAd). Acute serum cytokine increases post-dosing have been seen at the MTD of EnAd (“flat” dosing of 3 x 1012 vp on Days [D] 1, 3 and 5) [Machiels 2019]. Following supportive preclinical data [McElwaine-Johnn 2019], we explored if a LHH dosing regimen, in which a lower dose is given on D1 prior to two higher doses on D3 and 5, may improve vector safety/tolerability thereby allowing higher cumulative doses to be given. Methods: Data were pooled from three Phase 1 dose-escalation studies in advanced/metastatic epithelial cancer: SPICE (EnAd + pembrolizumab/nivolumab; NCT02636036), FORTITUDE (NG-350A ± pembrolizumab; NCT03852511) and STAR (NG-641; NCT04053283). Serum cytokines were measured using a 17-analyte Luminex assay. IL-6/MCP-1 data for D1, 3 and 5 (pre- and 6-10 hrs post-dose) were analyzed to examine acute cytokine changes. TNFα/IFNγ were examined due to their association with cytokine release syndrome (CRS). Samples analyzed from SPICE/FORTITUDE were taken before PD-1 inhibitor administration. Results: 84 patients (SPICE n=51; FORTITUDE n=18; STAR n=15) were included in these analyses; 79 had cytokine data. AEs and Gr≥3 AEs within 1 wk of first dose, and DLTs at any time, were less frequent with a LHH vs flat dosing regimen (Tbl). Importantly, a LHH dose of 1-6-6 (1 x 1012 vp on D1; 6 x 1012 vp on D3 and 5; greater than the previous flat MTD) was tolerated. Acute increases in TNFα/IFNγ were limited and no severe CRS was seen. Increases in IL-6/MCP-1 with 1 x 1011 or 1 x 1012 vp flat dosing were negligible, whereas acute increases in IL-6/MCP-1 were seen after the first dose of 3 x 1012 vp when given as a flat dose (negligible increases on D3/5). Notably, cytokine responses with 1-3-3 dosing (1 x 1012 vp on D1; 3 x 1012 vp on D3 and 5), including after the first 3 x 1012 vp dose on D3, were negligible. Cytokine responses after the first dose of 6 x 1012 vp in the 1-6-6 regimen were similar to those seen with the first dose of the flat 3 x 1012 vp regimen. Conclusions: LHH dosing appears to induce a desensitization mechanism allowing higher cumulative doses of T-SIGn vectors to be given without the associated acute reactions to viral infusions. This finding may have implications for optimizing safety-efficacy profiles of viral vectors in cancer. Clinical trial information: NCT02636036, NCT03852511 and NCT04053283. [Table: see text]

Purpose/objective The benefits of having a support system, such as social relationships with close friends and family, have been well documented for patients with serious health issues. As scientific evidence has shown, individuals who have the lowest level of involvement in social relationships face a greater mortality risk. Support systems, however, are not infallible. Relationship stress can have a negative impact on people-patient and caregiver alike-behaviorally, psychosocially, and physiologically. The purpose of this article is to encourage case managers who take a patient-centered approach to also consider the existence and extent of the support system, as well as any stresses or tensions that are observable within the support system. Although the case manager is ethically obliged to advocate for the individual receiving case management services, that advocacy can be extended to the support system for the good of all. Primary practice settings This discussion applies to numerous case management practices and work settings including (but not limited to) hospital-based case management, home health, geriatrics, catastrophic case management, mental health, palliative care, and end of life/hospice. Finding/conclusions As part of the assessment phase of the case management process, case managers determine the extent of the patient's support system or social support network such as family and close friends. Although their advocacy is primarily for the patient receiving case management services, case managers also become aware of the needs of the support system members as they face their loved one's serious illness, severe injury, geriatric care demands, or end of life. Case managers can use their communication skills, especially motivational interviewing, with patients and their support systems to identify stresses and issues that can impact the pursuit of health goals. In addition, case managers ensure that individuals and their support systems are kept informed such as about the health condition, stage of disease, plan of care, treatment options, and care transition plan. Implications for case management Professional case managers expand their role as advocates, serving primarily the patients ("clients") who receive case management services and also members of the support system. By becoming more aware and sensitive to the needs of the support system, case managers help reduce stress on the support system, which can contribute to positive outcomes for patients ("clients").

Purpose/objective Given the prevalence of mental health issues, particularly depressive disorders, in the U.S. population, professional case managers should increase their sensitivity to and awareness of mental illnesses, as well as their impact on physical health. Throughout the case management process, case managers frequently observe behaviors and symptoms such as those associated with depressive disorders. Case managers need to have, at a minimum, a working knowledge of mental and behavioral health issues and be familiar with basic screening tools. This will enable them to become more attuned to symptoms and behaviors that indicate that the individual should be further assessed and diagnosed by a physician. Primary practice setting Across the case management spectrum, including acute care, accountable care organizations, patient-centered medical homes, physician practices, clinics, occupational health clinics, workers' compensation, and other settings in which case managers work with individuals (clients who receive case management services) and their families/support systems. Findings/conclusions With more than one quarter of the U.S. population affected by a depressive disorder, professional case managers who practice holistically bring together the mental and physical aspects of health. This is particularly important in a health care system and among payer sources that continue to divide the two. Case managers elevate their practice by demonstrating a greater understanding of the interconnectedness of mental and physical health and can positively influence the transdisciplinary care team to take a person-centered approach to address all health issues, in pursuit of the individual's health goals. Implications for case management practice Professional case managers must increase their understanding of mental health, becoming more aware of "red flags" that may necessitate a further evaluation and assessment by a mental health professional. They should also hone their communication skills, particularly the use of motivational interviewing techniques, to encourage individuals to discuss their feelings, worries, fears, and anxiety, as well as any potential symptoms of depression, which may range from mild to severe. Without judgment or bias, the case manager, as the advocate, can provide the information, support, or other services needed to address mental health issues, to support and further the individual's health goals.

Purpose/objective Pain management, episodic and chronic, is a major issue in health care today, affecting more than 76 million people across care-delivery settings from acute care to rehabilitation, workers' compensation to primary care. As a result, professional case managers occupy an important role within an interdisciplinary care team to address pain as part of a comprehensive case management process, from intake and assessment through care delivery and transitions of care. Primary practice setting Pain management, as part of the comprehensive case management process, is applicable across the case management spectrum, including hospitals, accountable care organizations, patient-centered medical homes, physician practices, clinics, occupational health clinics, workers' compensation, and other settings in which case managers work with clients and their support systems. Findings/conclusions The prevalence of pain across the care continuum, affecting individuals at various stages of an individual's lifecycle, raises the importance of acute and chronic pain assessments as part of the overall case assessment. In addition to screening for pain, case management assessments must look for signs of depression, as well as the potential for abuse/misuse of opioid medications, which is an alarming public health threat. Given their clinical expertise, their roles as advocates, their ability to conduct a comprehensive client/patient assessment, and their expertise in using tools such as motivational interviewing, professional case managers-and particularly those who are board certified-occupy a central role in pain management as part of a patient-centered approach. Implications for case management practice Case managers must understand the impact of both pain and pain medications on the client's daily functions, from a health and safety perspective. Pain management should be examined through the lens of professional case management, and what a competent case manager can do to advocate for clients who are experiencing pain, whether acute or chronic, while facilitating the sharing of information among various members of an interdisciplinary care team and coordinating care.

TPS2668 Background: NG-350A is a transgene modified variant of the oncolytic platform virus enadenotucirev (EnAd) which expresses a fully human agonist anti-cluster of differentiation 40 (anti-CD40) antibody. The principal advantage of encoding anti-CD40 within an oncolytic virus is the ability to potentially achieve very high levels within the tumor coupled with direct cytotoxicity due to viral lysis and stimulation of the immune-system. NG-350A infects and selectively replicates in tumor cells. The anti-CD40 antibodies are expected to activate the patient’s own dendritic cells, macrophages and B-cells to drive CD4+ and CD8+ T-cell immuno-inflammatory responses and immune mediated tumor cell killing. EnAd is a tumor-selective chimeric Ad11/Ad3 group B oncolytic adenovirus developed using directed evolution. Phase I clinical studies have identified a well-tolerated systemic dose and regimen for EnAd monotherapy. EnAd shows a high level of selective replication and cell killing for a broad range of carcinoma cell lines (of epithelial origin) with little replication in normal and non-carcinoma cells. Methods: This first in human study will evaluate the safety, tolerability and preliminary efficacy of NG-350A together with virus kinetics, immunogenicity and other pharmacodynamic effects to elucidate the mechanism of action of NG-350A in patients with advanced or metastatic epithelial tumours. In the dose escalation phase up to 33 patients evaluable for dose-limiting toxicity will receive NG-350A by IV infusion on Day 1, 3 and 5 at 6 US sites. The first IV cohort in the dose-escalation phase will utilize the conventional ‘3+3’ design; thereafter dose recommendations will be based on a continual reassessment method. Following determination of the recommended phase 2 dose up to 20 patients will be treated in a dose-expansion cohort. In a parallel cohort, up to 12 patients will receive a single dose of NG-350A by intratumoural (IT) injection on Day 1 for direct delivery of high viral titres to tumor. Up to six patients are planned to undergo surgical resection of a tumor lesion to optimize translational research. Clinical conduct of the study was initiated in February 2019.

The ability of oligonucleotides to mediate the formation of inorganic materials is now well established. RNA and DNA are proving to be capable of mediating the formation of inorganic nanoparticles with sequence-specific control over nanoparticle size, shape, and even atomic-level crystallinity. Here we describe methods for isolating specific RNA sequences from large random sequence libraries that either bind to precut inorganic crystal wafers with high affinity or influence inorganic crystal growth.

Summary The intent of this article is to provide one company's perspective on the challenging and complex care management of the high-risk neonate. The strategies presented herein should enable and encourage case managers to implement an integrated management process for the frail neonatal population.

Moxalactam (LY127935; 6059S), a new broad-spectrum beta-lactam antibiotic, was used successfully with an aminoglycoside in a patient with Serratia marcescens meningitis complicating a neurosurgical procedure. With a bioassay method, peak and trough serum and cerebrospinal; fluid concentrations of moxalactam were determined during therapy. Mean peak and trough serum levels were 100.6 and 35.5 micrograms/ml, respectively. Corresponding mean peak and trough cerebrospinal fluid levels were 12.4 and 10.38 micrograms/ml. Cerebrospinal fluid levels of moxalactam exceeded the minimal bactericidal concentration for the infecting organism by more than 30-fold throughout therapy. No untoward effects of moxalactam were observed. Moxalactam may be a useful agent in the treatment of meningitis due to susceptible gram-negative bacilli.

Three clinical isolates of Staphylococcus aureus , which were previously shown to contain a 50S plasmid conferring resistance to several aminoglycosides, were examined for modifying enzymes. Both the wild-type and heat-cured derivatives of the isolates were screened for acetyl-, adenylyl-, and phosphotransferase activities. The substrates were gentamicin, amikacin, and netilmicin; the results indicated that even though all three activites were present, the phosphotransferase reaction was most responsible for resistance to these antibiotics. The absence of any of the modifying activites in cured derivatives of the three isolates supports the conclusion that aminoglycoside resistance in these strains is conferred by a plasmid.

Summary Hemagglutinins (HA) to O antigens from bacteria in urine were measured in serial serum specimens from patients with urinary tract infections. Twofold or greater HA rises were found in 51 of 105 bacteria from patients with acute infections of varying severity. HA rises to specific Escherichia, particularly strains possessing O antigens 4 and 6, were found primarily in patients with temperatures greater than 101° and in those with overt acute pyelonephritis. In these persons and in patients with chronic pyelonephritis high HA titers to heterologous E. coli O4 and O6 antigens were also found. Serologic and cultural findings of other Gram-negative bacteria were more randomly distributed. These serologic methods offer promise in documenting urinary tract infections and separating such severe infections as acute and chronic pyelonephritis from cystitis.

Arthropod-borne virus infections occurred in a small group of human subjects in Miami, Florida, in 1958. Serologic studies in four of the five cases reported herein indicate that St. Louis encephalitis virus or a closely related agent was the probable cause. Autopsy specimens in one case revealed microscopic evidence of viral encephalitis. These cases in Miami were associated in time with similar ones in Jamaica, Trinidad and the Republic of Panama; this points to an outbreak involving the Caribbean and adjacent areas. A survey of serum specimens obtained from sixty-four Miami residents prior to the outbreak revealed that six had neutralizing antibodies to one or more arthropod-borne viruses. Serologic evidence of infection with a group B arthropod-borne virus other than St. Louis encephalitis is presented. These findings suggest that Florida, together with the Caribbean Islands and the Spanish Main, is an endemic area of arthropod-borne virus disease.

Summary Antibody responses after 17D yellow fever (YF) vaccination in persons with no known previous arbovirus infection or only prior vaccination, were compared with similar measurements in those who had recovered from St. Louis encephalitis (SLE) or dengue. All of the eight subjects infected with SLE virus 20 to 69 months before, and five of eight with dengue six to 19 months earlier had a broad heterotypic hemagglutination-inhibiting (HI) antibody response to all eight antigens used, whereas the nine uninfected and the six prior vaccinated individuals developed HI antibodies to YF alone. Three persons with past dengue but with no changes in HI antibody titer after vaccination, had prevaccination HI antibody titers of 1:40 or more to at least one of the arbovirus antigens; only one of the five dengue subjects with HI antibody increases had prevaccination titers of this level. By contrast, the prevaccination titers in persons who had recovered from SLE infection were unrelated to their subsequent serologic responses. In addition to a heterotypic response, those who had recovered from both diseases had a greater homotypic response than did the others. HI antibodies to group B arboviruses were measured in 38 Miccosukee Indians of South Florida before and after 17D yellow fever vaccination. Initially, antibodies were present in only three individuals. Following vaccination all Indians showed a YF response and 14 developed a heterotypic response similar to that of persons with past SLE infection and dengue. The CF antibody responses after vaccination in general followed the same pattern as the HI responses but were at considerably low levels and were more variable. There was no firm correlation with prior group B arbovirus exposure and heterotypic CF responses. It is concluded that YF vaccination is a potent tool to recall past elevated HI titers of SLE and dengue antibodies for epidemiologic purposes in order to detect populations in which outbreaks of group B arbovirus infections have previously occurred and may recur.

Two strains isolated from a recent outbreak of infections by gentamicin-resistant Staphylococcus aureus were examined to determine whether genetic control of this resistance is plasmid or chromosomally mediated. Curing techniques indicated a plasmid location in both strains. Physical isolation and characterization of the plasmid deoxyribonucleic acid from one strain revealed that the determinant for gentamicin resistance resides on a 50S plasmid.

cultures of effluent on both days grew A. calcoaceticus var. anitratus. On the second day of infection a culture of the water bath used to warm dialysate bottles also yielded 19,000 colony-forming units per milliliter (du/ml) of the same organism, which also had the same antibiogram as that found in the patient's dialysis effluent. Gentamicin, administered via oddnumbered dialysates and in a single intravenous dose, resulted in sterile cultures of effluent and clearance of symptoms by the time dialysis was discontinued on the thirteenth hospital day. That evening peritoneal dialysis had to be resumed for 4 additional days. On the second day after its resumption and daily until discontinued, Candida albicans was cultured from effluent. The patient remained asymptomatic, and Gram stains of the effluent were negative for bacteria, yeasts, and hyphae, but showed numerous PMNLs. On the twenty-eighth hospital day the patient died of aspiration pneumonia. While autopsy findings included purulent ascites, peritonitis, and a cul-de-sac abscess, cultures were not obtained.

A 21-year old man sustained multiple facial fractures and skin lacerations during an automobile accident, with resultant necrosis of the left upper eyelid and exposure of the cornea. Bacterial and secondary fungal corneal ulceration and perforation occurred, leading to enucleation. Cultures from the noninfected anophthalmic orbit approximately eight weeks after enucleation yielded Pseudomonas pseudomallei. This is the second isolate of this domallei. This is the second isolate of this organism in the United States and the first apparent association with the ocular adnexa.

This paper describes the implementation of a computerized nosocomial infection control system for a 500-bed tertiary-care teaching hospital. It is implemented on a minicomputer that uses the relational data base management system INGRES, which is marketed by Relational Technology, Inc. This system, which replaces a manual one that depended on "needle sort" data cards, is designed to provide for entry of infection data that have been collected onto abstracting forms; decision support in the prospective analysis of suspicious infection rates or trends; generation of monthly, on-demand, and annual infection rate reports; retrospective interrogation and analysis of infection data for rates and trends that may explain or clearly indicate the sources of in-hospital (nosocomial) infections; updating of infection records as additional infection-related data become available and known to the hospital's infection control team; and ad hoc analysis and comparisons between data on control and infected patients, both prospectively and retrospectively.

Excerpt To the editor: It appears that a prankster has inserted the final paragraph into the report of an interesting and well-done study, "Cutaneous Abscesses. Anaerobic and Aerobic Bacteriology a...

The area between research advances and their utilization in clinical microbiology laboratories needs special thought. Antibody titers, serogrouping, and antibody-coated bacteria are data most helpf...