EXECUTIVE SUMMARYMonitoring multidrug-resistant organisms (MDROs) and the infections they cause in a healthcare setting is important to detect newly emerging antimicrobial resistance profiles, to identify vulnerable patient populations, and to assess the need for and effectiveness of interventions; however, it is unclear which metrics are the best, because most of the metrics are not standardized. This document describes useful and prac tical metrics and surveillance considerations for measuring MDROs and the infections they cause in the practice of in fection prevention and control in healthcare settings. These metrics are designed to aid healthcare workers in docu menting trends over time within their facility and should not be used for interfacility comparison.The following MDROs are addressed: (1) methicillin-re sistant Staphylococcus aureus; (2) vancomycin-resistant En terococcus species; (3) multidrug-resistant gram-negative ba cilli; and (4) vancomycin-resistant S. aureus. We convened a working group of experts that reviewed current practices, the peer-reviewed literature, and existing guidelines on surveil lance strategies and key metrics.We propose that healthcare facilities use the following 4 routine metrics to monitor MDROs and the infections they cause: (1) an MORO-specific line list for tracking patients who have acquired an MDRO; (2) an antibiogram for mon itoring susceptibility patterns of isolates recovered from pa tients; (3) the incidence of hospital-onset MDRO bacteremia, which is an objective, laboratory-based metric that is highly associated with invasive disease and does not require chart review to estimate infection burden; and ( 4) clinical culture results, to measure incidence of infection or colonization, to quantify the number of people whose MORO acquisition is healthcare associated. In addition, healthcare facilities may want to calculate both the overall prevalence of carriage and the prevalence of carriage at admission, the latter of which can be useful in detecting importation of methicillin-resistant S. aureus into healthcare facilities, to estimate the exposure burden. Active surveillance testing can augment and increase the accuracy of some metrics. Healthcare facilities not per forming active surveillance testing might wish to consider point-prevalence screening, to help assess how much the number of positive clinical culture results underestimates the hidden reservoir of MDROs. It is important to understand the limitations of all proxy metrics. Because of the paucity of published research findings focused on this area of study, most recommendations were based on opinion and were heavily influenced by the perceived usefulness and simplicity of the metric for assessing MDROs in the hospital setting and for determining the impact of interventions.

Culture of human peripheral blood lymphocytes (PBL) in partially purified and lectin-free interleukin 2 results in the generation of cytotoxic effector cells which have the unique property of lysing natural killer (NK)-resistant fresh human tumor cells. We have termed these effector cells "lymphokine- activated killer" cells (LAK). LAK are generated from both normal and cancer patients' PBL and are able to lyse both autologous and allogeneic tumor cells from all histologic tumor types tested. Our previous studies suggested that the LAK phenomenon was distinct from either the cytotoxic thymus-derived lymphocyte (CTL) or NK systems based on a variety of criteria. This study reports that the cell type involved is also distinct, as determined by phenotypic characteristics. The LAK effector cell phenotype was analyzed in parallel with alloimmune CTL, and LAK were found to be similarly susceptible to the monoclonal anti-T cell antibodies OKT-3 or OKT-8 plus complement. In contrast the LAK precursor was not susceptible to the OKT-3 or Leu-1 antibodies plus complement, while the ability to generate alloimmune CTL was totally obliterated when tested using the same PBL responder population; in fact, generation of LAK was found to be augmented five- to sixfold, clearly suggesting that LAK precursor cells are not T lymphocytes as defined by these antibodies. LAK precursors were found to be abundant in NK cell-enriched Percoll gradient fractions, which had been depleted of the 29 degrees C E- rosetting "high affinity" T cells. However, LAK precursors were found to be distinct from the majority of NK cells since lysis of fresh PBL with the monoclonal antibodies OKM-1, Leu-7, or OKT-11 significantly depleted or totally eliminated NK activity, while subsequent activation of the remaining cells generated high levels of LAK and in some cases augmented levels of LAK. LAK precursors were found to be distributed in the thymus, bone marrow, spleen, lymph node, and thoracic duct in addition to the PBL. Therefore, while the cell(s) responsible for activation and expression of LAK activity have some common features with the classic T cell-mediated CTL and NK cell systems, the LAK precursor cells are clearly distinct as determined by phenotype analysis using monoclonal antibodies and complement, and at present must be classified as a "null" cell.

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The Towne strain cytomegalovirus and a low-passage strain, Toledo-1, were compared for virulence and immunogenicity in healthy adult male subjects to determine the suitability of the Towne strain for vaccination. Five seropositive subjects who received the Toledo-1 strain developed infections ranging in severity from laboratory abnormalities to mild mononucleosis syndromes (mean incubation, 4.7 weeks). None of the four seronegative subjects receiving the Towne strain developed systemic infection, but all developed delayed local reactions at the injection sites. All subjects developed cytotoxic lymphocyte responses specific to cytomegalovirus, usually HLA-restricted, but these were of greater magnitude and duration in the Toledo-1 recipients. The latter also developed natural killer cell and interferon responses, atypical lymphocytosis, inversion of helper/suppressor cell ratios, and depressed responses to T-cell mitogens, none of which occurred in Towne strain recipients. The results further substantiate the avirulence and immunogenicity of the Towne strain cytomegalovirus.