Invasive Methicillin-Resistant Staphylococcus aureus USA500 Strains from the U.S. Emerging Infections Program Constitute Three Geographically Distinct Lineages.

USA500 isolates are clonal complex 8 (CC8) Staphylococcus aureus strains closely related to the prominent community- and hospital-associated USA300 group. Despite being relatively understudied, USA500 strains cause a significant burden of disease and are the third most common methicillin-resistant S. aureus (MRSA) strains identified in the U.S. Emerging Infections Program (EIP) invasive S. aureus surveillance. To better understand the genetic relationships of the strains, we sequenced the genomes of 539 USA500 MRSA isolates from sterile site infections collected through the EIP between 2005 and 2013 in the United States. USA500 isolates fell into three major clades principally separated by their distribution across different U.S. regions. Clade C1 strains, found principally in the Northeast, were associated with multiple IS256 insertion elements in their genomes and higher levels of antibiotic resistance. C2 was associated with Southern states, and E1 was associated with Western states. C1 and C2 strains all shared a frameshift in the gene encoding AdsA surface-attached surface protein. We propose that the term "USA500" should be used for CC8 strains sharing a recent common ancestor with the C1, C2, and E1 strains but not in the USA300 group.IMPORTANCE In this work, we have removed some of the confusion surrounding the use of the name "USA500," placed USA500 strains in the context of the CC8 group, and developed a strategy for assignment to subclades based on genome sequence. Our new phylogeny of USA300/USA500 will be a reference point for understanding the genetic adaptations that have allowed multiple highly virulent clonal strains to emerge from within CC8 over the past 50 years.

Diabetes mellitus and extrapulmonary tuberculosis: site distribution and risk of mortality.

Scarce data exist on the relationship between diabetes and extrapulmonary tuberculosis (EPTB). We evaluated whether diabetes impacts site of TB and risk of death in patients with EPTB. We evaluated a cohort of TB cases from the state of Georgia between 2009 and 2012. Patients aged ⩾16 years were classified by diabetes status according to medical records. Site of EPTB was determined by culture and/or state TB classification. Death was defined by all-cause mortality. Of 1325 eligible reported TB cases, 369 (27·8%) had any EPTB including 258 (19·5%) with only EPTB and 111 (8·4%) with pulmonary TB and EPTB. Of all TB cases, 158 had diabetes (11·9%). In multivariable analysis, the odds of any EPTB was similar in patients with and without diabetes [adjusted odds ratio 1·04, 95% confidence interval (CI) 0·70-1·56]. The risk of death was 23·8% in patients with EPTB and diabetes vs. 9·8% in those with no diabetes (P < 0·01); after adjusting for covariates the difference was not significant (aRR 1·19, 95% CI 0·54-2·63). Diabetes was common in patients with EPTB and risk of death was high. Improved understanding of the relationship between diabetes and EPTB is critical to determine the extent that diabetes affects TB diagnosis and clinical management.

Clinical and laboratory characteristics of invasive infections due to methicillin-resistant Staphylococcus aureus isolates demonstrating a vancomycin MIC of 2 micrograms per milliliter: lack of effect of heteroresistant vancomycin-intermediate S. aureus phenotype.

We describe clinical and laboratory characteristics of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections with vancomycin MICs of 2 µg/ml and compare heteroresistant-intermediate S. aureus (hVISA) to non-hVISA. Health care-associated community-onset infections were the most common and resulted in frequent complications and relapses. hVISA-infected patients were more likely to have been hospitalized in the year prior to MRSA culture.

Surveillance for severe community-associated methicillin-resistant Staphylococcus aureus infection.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has rapidly emerged in the USA as a cause of severe infections in previously healthy persons without traditional risk factors. We describe the epidemiology of severe CA-MRSA disease in the state of Georgia, USA and analyse the risk of death associated with three different clinical syndromes of CA-MRSA disease - pneumonia, invasive disease, and skin and soft-tissue infections (SSTIs). A total of 1670 cases of severe CA-MRSA disease were reported during 2005-2007. The case-fatality rate was 3.4%; sex and race of fatal and non-fatal cases did not differ significantly. While CA-MRSA pneumonia and invasive disease were less common than SSTIs, they were about 15 times more likely to result in death [risk ratio 16.69, 95% confidence interval (CI) 10.28-27.07 and 13.98, 95% CI 7.74-25.27, respectively]. When controlling for age and the presence of other clinical syndromes the odds of death in patients manifesting specific severe CA-MRSA syndromes was highest in those with pneumonia (odds ratio 11.34). Possible risk factors for severe CA-MRSA SSTI and pneumonia included the draining of lesions without medical assistance and an antecedent influenza-like illness.

Synthesis and biological evaluation of amide derivatives of (5,6-dimethoxy-2,3-dihydro-1H-inden-1-yl)acetic acid as anti-inflammatory agents with reduced gastrointestinal ulcerogenecity.

A variety of amide derivatives of (5,6-dimethoxy-2,3-dihydro-1H-inden-1-yl)acetic acid were synthesized and screened for their analgesic and anti-inflammatory activities. The compounds were found to have longer activity profile exceeding that of indomethacin in carrageenan-induced rat paw edema model. Few selected compounds were also screened for their antipyretic, anti-arthritic and ulcerogenecity potential. From these studies it can be concluded that these compounds though have significant antipyretic activity did not act through the inhibition of TNF-alpha. The test compounds failed to prevent the development of secondary inflammation in adjuvant-induced arthritis assay. However, these compounds showed no ulcer formation at the tested dose level of 100 mg/kg p.o.

Aromatic amide derivatives of 5,6-dimethoxy-2,3-dihydro-1H-inden(-1-yl)acetic acid as anti-inflammatory agents free of ulcerogenic liability.

Amide derivatives of 5,6-dimethoxy-2,3-dihydro-1H-inden(-1-yl)acetic acid were synthesized and evaluated for their anti-inflammatory and analgesic activity. Few selected compounds were also screened for their antipyretic, anti-arthritic, and ulcerogenic potential. Most of the compounds exhibited good activity profile and were free of gastrointestinal toxicity of common NSAIDs. However these compounds failed to decrease secondary lesions of adjuvant induced arthritis and also did not inhibit TNF-alpha in lipopolysaccharide induced pyresis.

Effect of dissolved organic matter on the uptake of trace metals by American oysters.

To examine the effects of dissolved organic matter on metal bioavailability, uptake of trace metals (Cd, Co, Hg, Cr, Ag, Zn) by American oysters (Crassostrea virginica) was compared between treatments with different dissolved organic carbon (DOC) concentrations and contrasting low molecular weight (LMW, 1 kDa) and high molecular weight (HMW, 1 kDa-0.2 micron) DOC fractions, using radiotracer techniques and short-term exposure experiments. Uptake rate constants (mL g-1 h-1) of metals, in general, increased with increasing DOC concentrations, with an initial decrease at lower DOC concentrations. Oyster dry weight concentration factors (DCF, mL g-1), determined at the end of exposure experiments (8 h), also increased for Cd, Co, Cr, Ag, and Zn, but decreased for Hg, with increasing DOC concentrations. Changes of metal uptake rate constants and DCF values with DOC concentration suggest that metal uptake pathways by American oysters vary from predominantly uptake (by diffusion of neutral) of free ionic, inorganically complexed, and LMW organic ligand complexed metals at very low DOC concentration to direct ingestion and digestion of HMW or colloidally complexed metals at higher DOC concentrations. Measured partition coefficients (Kc) between dissolved and colloidal phases were comparable between metals, ranging from 10(5.12) to 10(5.75) mL g-1. However, DCF values and uptake rate constants differed considerably between metals, with the highest DCF values and uptake rate constants found for B-type metals, e.g., Ag, Hg, Zn, and Cd, and the lowest ones for several intermediate-type metals (e.g., Co, Cr). Metal types and thus the interaction of metals with organic ligands, such as strong complexation of B-type metals with S-containing organic ligands, may play an important role in the bioavailability and toxicity of metals to aquatic organisms. Differences in metal uptake in contrasting LMW and HMW DOC treatments suggest a generally depressed bioavailability of colloidally complexed metals at low DOC concentration (0.5 ppm) but a generally enhanced uptake at higher DOC concentrations.

The influence of the composition of the nursing staff on primary bloodstream infection rates in a surgical intensive care unit.

OBJECTIVES: To determine the risk factors for acquisition of nosocomial primary bloodstream infections (BSIs), including the effect of nursing-staff levels, in surgical intensive care unit (SICU) patients. DESIGN: A nested case-control study. SETTING: A 20-bed SICU in a 1,000-bed inner-city public hospital. PATIENTS: 28 patients with BSI (case-patients) were compared to 99 randomly selected patients (controls) hospitalized > or =3 days in the same unit. RESULTS: Case- and control-patients were similar in age, severity of illness, and type of central venous catheter (CVC) used. Case-patients were significantly more likely than controls to be hospitalized during a 5-month period that had lower regular-nurse-to-patient and higher pool-nurse-to-patient ratios than during an 8-month reference period; to be in the SICU for a longer period of time; to be mechanically ventilated longer; to receive more antimicrobials and total parenteral nutrition; to have more CVC days; or to die. Case-patients had significantly lower regular-nurse-to-patient and higher pool-nurse-to-patient ratios for the 3 days before BSI than controls. In multivariate analyses, admission during a period of higher pool-nurse-to-patient ratio (odds ratio [OR]=3.8), total parenteral nutrition (OR=1.3), and CVC days (OR=1.1) remained independent BSI risk factors. CONCLUSIONS: Our data suggest that, in addition to other factors, nurse staffing composition (ie, pool-nurse-to-patient ratio) may be related to primary BSI risk. Patterns in intensive care unit nurse staffing should be monitored to assess their impact on nosocomial infection rates. This may be particularly important in an era of cost containment and healthcare reform.

Tuberculosis in the inner city: impact of a continuing epidemic in the 1990s.

Tuberculosis cases have recently declined in the United States, renewing interest in disease elimination. We examined the epidemiology of tuberculosis from 1991 through 1997 at an inner-city public hospital and assessed population-based tuberculosis rates by ZIP code in the 8 metropolitan Atlanta counties. During the 7 years, 1378 new patients had tuberculosis diagnosed at our hospital (mean, 197 patients/year), accounting for 25% of tuberculosis cases in Georgia. Coinfection with human immunodeficiency virus (HIV) was common, but a significant decrease in the proportion of HIV-infected patients with tuberculosis was noted over time. Most patients were members of a minority group (93%) and were born in the United States (96%). Two inner-city ZIP code areas had annual tuberculosis rates >120 cases per 100,000 persons, and 8 ZIP code areas had annual rates of 47-88 cases per 100,000 persons between 1993 and 1997, compared with the annual national average of 8.7 cases per 100,000 persons. Our hospital continues to care for large numbers of tuberculosis patients, and rates of tuberculosis remain high in the inner city. These data mandate a concentration of efforts and resources in urban locations if tuberculosis control and elimination is to be achieved in the United States.

Epidemiology of device-associated infections related to a long-term implantable vascular access device.

OBJECTIVE: To examine risk factors for, and determine the incidence of, device-associated infections among patients with an implantable vascular access device. SETTING: Grady Health System, including a 1,000-bed, inner-city, public, teaching hospital and human immunodeficiency virus (HIV), oncology, and sickle cell clinics in Atlanta, Georgia. PATIENTS: 123 consecutive patients who received a PAS-Port implantable venous access device between January 1 and June 30, 1995. DESIGN: Retrospective cohort study with follow-up > or = 1 year following device implantation. RESULTS: Underlying illnesses included HIV infection in 66 patients (median CD4 count, 24.4 cells/mm3), malignancy in 51, and sickle cell disease in 6. Mean age of patients was 43.7 years, 50% were male, and 74% were black. Thirty-one (25%) of 123 patients developed a primary or device-associated bloodstream infection (BSI), and 3 of the 31 patients experienced two separate episodes of infection. The overall rate of infection was 1.23 primary BSIs per 1,000 device days. Patients with cancer had a lower rate of infection than those with HIV infection, but the difference was not statistically significant (0.96 vs 1.50 BSIs/1,000 device days; relative risk, 0.58; 95% confidence interval, 0.27-1.26). Subgroup analysis of patients with different malignancies indicated that infection rates differed according to type of cancer, and there was a trend for heterogeneity across the different cancer strata (P=.06). Gram-positive pathogens accounted for 60% of the pathogens recovered. Six (19%) of 31 patients who developed an infection did so within the first 14 days after implantation. In 11 (32%) of the 34 BSIs, the port required removal; two patient deaths were attributed to device-associated bacteremias (0.072 deaths/1,000 device days). CONCLUSIONS: Approximately one fourth of patients who had a vascular access device implanted developed a primary BSI, but the overall infection rate (per 1,000 device days) was relatively low, even among those with HIV infection. Primary BSI rates in patients with vascular access devices appeared to differ according to the specific underlying illness.

Pollen tube guidance by the female gametophyte.

In flowering plants, pollen grains germinate on the pistil and send pollen tubes down the transmitting tract toward ovules. Previous genetic studies suggested that the ovule is responsible for long-range pollen tube guidance during the last phase of a pollen tube's journey to the female gametes. It was not possible, however, to unambiguously identify the signaling cells within an ovule: the haploid female gametophyte or the diploid sporophytic cells. In an effort to distinguish genetically between these two possibilities, we have used a reciprocal chromosomal translocation to generate flowers wherein approximately half the ovules do not contain a functional female gametophyte but all ovules contain genotypically normal sporophytic cells. In these flowers, pollen tubes are guided to the normal but not to the abnormal female gametophytes. These results strongly suggest that the female gametophyte is responsible for pollen tube guidance, but leave open the possibility that the gametophyte may accomplish this indirectly through its influence on some sporophytic cells.

Nosocomial exposure to parvovirus B19: low risk of transmission to healthcare workers.

OBJECTIVE: To evaluate the risk of nosocomial transmission of parvovirus B19 (B19) infection to healthcare workers (HCWs) exposed to patients with transient aplastic crisis (TAC) caused by acute B19 infection. DESIGN: Cohort study. SETTING: 1,000-bed, urban teaching hospital in Atlanta, Georgia. PARTICIPANTS: Eighty-seven exposed HCWs who cared for two patients with TAC prior to the time they were isolated and a comparison group of 88 unexposed HCWs from wards or clinics where the patients did not receive care. INTERVENTION: Self-administered questionnaire on hospital contact with index patients, B19 community risk factors, and signs and symptoms suggestive of B19 disease. Serology for B19-specific IgM and IgG antibodies measured by antibody-capture enzyme-linked immunosorbent assay. RESULTS: 1 (3.1%) of the 32 nonimmune exposed HCWs had serologic evidence of recent B19 infection compared to 3 (8.1%) of the 37 nonimmune HCWs in the comparison group (P = .6). In a subgroup analysis of exposed HCWs who cared for index patients during the time when the virus load was expected to be greatest, a recent infection rate of 5.8% (1/17) was found among nonimmune HCWs. CONCLUSIONS: The finding of similar rates of recent infection in nonimmune exposed and unexposed HCWs suggests that transmission to HCWs did not occur, despite failure to place the patients in isolation at the onset of hospitalization.

Alpha 1-adrenergic receptor antagonist blocks acute cocaine action on the compound action potential of the auditory nerve in the chinchilla.

Acute systemic cocaine injection is known to significantly decrease the compound action potential (CAP) amplitude of the auditory nerve. In an attempt to elucidate the mechanism underlying this phenomenon, the present study investigated the influence of prazosin, an adrenergic alpha 1-receptor antagonist, on the effect of cocaine on the CAP. Amplitude-intensity functions at 1 and 8 kHz were obtained before and after treatment with cocaine (experimental group) or saline (control group) in prazosin pretreated subjects. The characteristic reduction in CAP amplitude after an acute cocaine injection was blocked by 0.05 mg/kg prazosin. When subjects were re-injected with cocaine or saline one h after prazosin, the reduction in CAP amplitude following cocaine injection had recovered.

Preventing the nosocomial transmission of tuberculosis.

OBJECTIVE: To study the efficacy of expanded tuberculosis infection control measures consisting primarily of administrative controls. DESIGN: Descriptive case series. SETTING: University-affiliated, inner-city hospital. INTERVENTIONS: Introduction of expanded tuberculosis infection control measures (including an expanded respiratory isolation policy). MEASUREMENTS: The number of tuberculosis exposure episodes and skin test conversion rates of health care workers were measured before and after implementation of expanded infection control measures. Tuberculosis exposure episodes (the number of patients who were not placed in respiratory isolation at admission but who subsequently had a diagnosis of acid-fast bacilli smear-positive pulmonary tuberculosis during that admission or within 2 weeks of discharge) were compared for two time periods: the 8 months before and the 28 months after implementation of infection control measures. Tuberculin skin test conversion rates among health care workers were evaluated during a 2.5-year period. RESULTS: After expanded infection control measures were implemented, the number of tuberculosis exposure episodes decreased from 4.4 per month (35 episodes among 103 patient admissions for potentially infectious tuberculosis over 8 months) to 0.6 per month (18 episodes among 358 patient admissions for smear-positive pulmonary tuberculosis over 28 months) (odds ratio, 9.72; 95% CI, 4.99 to 19.25 [P < 0.001]). The cumulative number of days per month that potentially infectious patients with tuberculosis were not in isolation decreased from 35.4 to 3.3 (P < 0.001). A concomitant decrease in tuberculin skin test conversion rates in health care workers was seen; 6-month tuberculin skin test conversion rates decreased steadily from 3.3% (118 conversions in 3579 health care workers; 1/92 to 6/92), 1.7%, 1.4%, 0.6%, to 0.4% (23 conversions in 5153 workers [1/94 to 6/94]) (P < 0.001). CONCLUSIONS: Infection control measures effectively prevented nosocomial transmission of tuberculosis to health care workers. Administrative controls appear to be the most important component of a tuberculosis infection control program and should be the first focus of such a program, especially at public hospitals, where resources are most likely to be limited.

Instantaneous Reproductive Effort in Female American Oysters, Crassostrea virginica, Measured by a New Immunoprecipitation Assay.

An immunoprecipitation assay was developed for measuring instantaneous reproductive effort in female American oysters, Crassostrea virginica. Oysters were injected with 14C-leucine and incubated in situ for 1 to 30 h periodically throughout the annual gametogenic cycle. Gonadal protein labeled with 14C-leucine was precipitated from an oyster homogenate with rabbit anti-oyster egg IgG as the primary antibody. Antibody-oyster egg protein complex was further purified by immunoadsorption with staphylococcal protein A cell suspension. The quantity of oyster eggs was determined by single-ring immunodiffusion. A mathematical model was developed to calculate the instantaneous reproductive rate of oysters and to estimate the number of days required from the initiation of gonadal development to spawning. The oyster population was lightly to moderately infected with a protozoan parasite, Perkinsus marinus. A negative correlation between the intensity of infection and the rate of gonadal production suggests that P. marinus retards the rate of gamete development. The seasonal cycle of gamete production determined by direct measurements of egg protein production was not equivalent to that determined by standard gonadal-somatic index (GSI), except at the most basic level. GSI was highest during the spring spawning peak, but the rate of gamete production was highest in the fall. Accordingly, the two measurements, rate versus standing crop (volume of gonad), reveal a substantially different picture about the details of the spawning season. Estimates of the time required to reach spawning condition ranged from several weeks to 1 or 2 months; these values agree with published estimates derived from less direct methods. Direct rate measurements thus seem to accurately reflect the true rate at which gametic tissue is produced in the field. A positive correlation between oyster size and the estimated days to spawn suggests that larger oysters require longer to prepare to spawn. Furthermore, the range in observed somatic and gametic growth emphasizes the conservatism of somatic growth and the volatility of gonadal growth that is borne out by the results of population dynamics models of oysters.

Differential effects of atrial natriuretic peptide infusion at physiological doses in different postures in humans.

To evaluate potential physiological actions of atrial natriuretic peptide (ANP) in humans, normal male volunteers were studied in the supine and head-up tilt positions both in the absence and presence of an ANP infusion at a rate which increased plasma ANP levels to ranges observed during physiological stimuli such as volume expansion. Infusion of ANP in the supine position provoked a significant natriuresis and diuresis and suppressed aldosterone secretion. Head-up tilt alone caused expected decreases in urine flow rate and the absolute and fractional excretion rates of sodium and increases in plasma renin activity and aldosterone levels. The combination of head-up tilt and ANP infusion resulted in a less marked decrease in urine flow rate and sodium excretion and a similar increase in plasma renin activity. However, there was a significant decrease in plasma aldosterone levels. These data support a physiologic action of ANP on renal and adrenal function.

Studies on non-steroidal anti-inflammatory and related biological activities of 5-(indan-1'-yl)tetrazoles and their intermediates.

Anti-inflammatory, analgesic and anti-pyretic activities of three new 5-(Indan-1'-yl)tetrazoles and anti-inflammatory activity of corresponding carboxamides were compared to those of standard drugs, phenylbutazone and aspirin. The results indicated 5-(Indan-1'-yl)tetrazole as the most promising compound in chronic anti-inflammatory and anti-pyretic tests.

Peritonitis following colonoscopy in a peritoneal dialysis patient.

A 65-year-old woman on continuous ambulatory peritoneal dialysis (CAPD) developed blood-tinged dialysate and bacterial peritonitis following a colonoscopic polypectomy. She grew multiple anaerobic organisms in her dialysate despite antibiotic prophylaxis with vancomycin and gentamicin prior to the procedure. This case confirms the need for broad spectrum antibiotic prophylaxis prior to colonoscopic procedures, especially if polypectomy is planned. The antibiotic chosen should cover anaerobes as well as gram-positive and gram-negative enteric organisms. We suggest the use of ampicillin, clindamycin, and an aminoglycoside antibiotic for this prophylaxis.