Investigation of the First Seven Reported Cases of Candida auris, a Globally Emerging Invasive, Multidrug-Resistant Fungus-United States, May 2013-August 2016.

November 11, 2016/65(44);1234-1237. What is already known about this topic? Candida auris is an emerging pathogenic fungus that has been reported from at least a dozen countries on four continents during 2009-2015. The organism is difficult to identify using traditional biochemical methods, some isolates have been found to be resistant to all three major classes of antifungal medications, and C. auris has caused health care-associated outbreaks. What is added by this report? This is the first description of C. auris cases in the United States. C. auris appears to have emerged in the United States only in the last few years, and U.S. isolates are related to isolates from South America and South Asia. Evidence from U.S. case investigations suggests likely transmission of the organism occurred in health care settings. What are the implications for public health practice? It is important that U.S. laboratories accurately identify C. auris and for health care facilities to implement recommended infection control practices to prevent the spread of C. auris. Local and state health departments and CDC should be notified of possible cases of C. auris and of isolates of C. haemulonii and Candida spp. that cannot be identified after routine testing.

An in vitro evaluation of disinfection protocols used for needleless connectors of central venous catheters.

UNLABELLED: A repeatable and sensitive method to evaluate the effect of three antiseptics and two disinfection techniques on viable micro-organisms on luer-activated catheter needleless connectors (NCs) was developed. NCs were inoculated with Staphylococcus epidermidis or Klebsiella pneumoniae and disinfected with 3·15% chlorhexidine gluconate + 70% isopropanol (CGI), 70% isopropanol (IPA) or 10% PVP povidone-iodine (PI) antiseptic pads using: (i) scrubbing the NC septum and threaded external surfaces or (ii) wiping only the surface of the septum. Treatments were also evaluated against NCs pretreated with human serum and exposed for 18 h to Staph. epidermidis prior to testing. Viable cells were quantified by plate count. The method for inoculation and recovery of luminal micro-organisms was repeatable (SD, 0·31; n = 28). IPA disinfection provided an approximate 3 log10  CFU reduction; CGI and PI provided 3-4 log10 reductions. PI and CGI were more effective than IPA (P < 0·05), but differences between CGI and PI were not significant for either disinfection method. IPA, but not CGI and PI was also less effective (P < 0·05) against NCs inoculated with Kl. pneumoniae than Staph. epidermidis. Pretreatment with serum and prolonged Staph. epidermidis inoculation removed the advantage seen with CGI and PI; log10 reductions were 1·80, 1·73 and 2·50 for CGI, PI and IPA, respectively. PI or CGI may be more effective than IPA for NC disinfection but effectiveness may be reduced on NCs contaminated with blood or serum. SIGNIFICANCE AND IMPACT OF THE STUDY: sensitive and repeatable protocol was developed to evaluate antiseptics for disinfecting catheter needleless connectors (NCs). Povidone-iodine (PI) and chlorhexidine gluconate plus isopropanol (CGI) were more effective than isopropanol (IPA) for reducing Staphylococcus epidermidis contamination of NCs. The effectiveness of PI and CGI was reduced on NCs pre-exposed to human serum and prolonged bacterial inoculation. IPA was also less effective against NCs contaminated with Klebsiella pneumoniae.

Staphylococcus aureus community-onset pneumonia in patients admitted to children's hospitals during autumn and winter of 2006-2007.

Staphylococcus aureus is a relatively uncommon cause of community-onset pneumonia (COP) that may complicate influenza infection. We reviewed admissions to children's hospitals to describe more systematically this entity. Records of patients hospitalized at three children's hospitals between 1 October 2006 and 30 April 2007 who had a positive S. aureus culture from a sterile site or respiratory specimen were reviewed and data were abstracted for episodes of primary S. aureus COP. Overall, 30 episodes met criteria for primary S. aureus COP; 12 (41%) involved methicillin-resistant S. aureus. Patients in 11 (37%) episodes were seen by a healthcare provider for their symptoms prior to hospital admission; three received an antimicrobial, none of which had activity against the S. aureus isolated. Mechanical ventilation was required in 21 (70%) episodes; five (17%) patients died. When evaluating patients with severe COP, providers should be aware of the potential for S. aureus, including methicillin-resistant strains.

Direct Detection of Carbapenem-Resistant Organisms from Environmental Samples Using the GeneXpert Molecular Diagnostic System.

In this pilot study, traditional culture and PCR methods were compared to the Cepheid GeneXpert IV molecular diagnostic system with the Xpert Carba-R assay (Carba-R assay) for detection of carbapenem resistance genes in primary environmental samples collected during a health care-related outbreak. Overall, traditional culture-dependent PCR and the Carba-R assay demonstrated 75% agreement. The Carba-R assay detected carbapenemase genes in five additional samples and in two samples that had additional genes when compared to culture-dependent PCR. The Carba-R assay could be useful for prioritizing further testing of environmental samples during health care-related outbreaks.IMPORTANCE Use of the Carba-R assay for detection of carbapenem-resistant Gram-negative organisms (CROs) can provide data for implementation of a rapid infection control response to minimize the spread of CROs in the health care setting.

Long-term xanthine therapy of asthma. Enprofylline and theophylline compared. International Enprofylline Study Group.

BACKGROUND: Enprofylline is a new xanthine derivative that shares theophylline's bronchodilator properties but is free of theophylline's adenosine receptor antagonist activity. We compared the long-term efficacy and tolerability of enprofylline and theophylline given over a 1-year period to adults with asthma. METHODS: Patients were recruited from 18 centers and 4 countries to participate in a 1-month double-blind comparison of enprofylline or theophylline in the treatment of asthma and were subsequently maintained on a regimen with the assigned medication for a further 11 months. The dosage of each xanthine was incremented from 150 mg twice daily at initiation to 300 and later 450 mg twice daily depending on the patient's tolerance and, in the case of theophylline, the rapidly assayed serum theophylline level. Patients kept a diary in which they recorded peak expiratory flow rate (PEFR) measured morning and evening, asthma symptom score, and the number of beta 2-agonists taken. Spirometry was checked at clinic visits at 3, 6, 9, and 12 months following randomization. RESULTS: Three-hundred forty-eight patients (174 enprofylline, 174 theophylline) participated in the trial. For both drugs there were significant improvements in PEFR and FEV1 during the first month of treatment with no significant difference between drugs (0.25 L for enprofylline vs 0.30 L for theophylline). Similarly, there were no differences in clinical outcome such as asthma exacerbations or beta 2-agonist usage between the two groups over follow-up. However, inhaled steroid dosage was more likely to have been incremented in theophylline-treated than enprofylline-treated patients (18% vs 8%, p = 0.025). Both drugs produced a modest increase in heart rate throughout the trial (approximately 5 beats/min). In 31 patients (26 enprofylline, 5 theophylline), asymptomatic elevations in aspartate aminotransferase and/or alanine aminotransferase occurred at least once during the study. In five patients (four enprofylline, one theophylline), the increase exceeded three times the upper limit of the normal range. In some subjects receiving enprofylline, serum enprofylline levels rose progressively despite constant oral dosage of the drug. CONCLUSIONS: Long-term xanthine therapy is well-tolerated by most adult asthmatics. However, long-term enprofylline administration may be associated with elevation in liver enzyme levels and unpredictable blood levels, thereby limiting its clinical usefulness.

Increase in community-acquired methicillin-resistant Staphylococcus aureus at a Naval Medical Center.

A retrospective review of methicillin-resistant Staphylococcus aureus isolates from the Naval Medical Center, San Diego, for the years 1994 through 1997, found that the annual number of community-acquired MRSA isolates increased during the period. These outpatient isolates were more likely than inpatient isolates to be sensitive to a greater number of antibiotics.

16alpha-bromoepiandrosterone, a dehydroepiandrosterone (DHEA) analogue, inhibits Plasmodium falciparum and Plasmodium berghei growth.

Dehydroepiandrosterone (DHEA) and its analogue, 16alpha-bromoepiandrosterone (alpha-epi-Br), may have activity against viral and parasitic infections, including human immunodeficiency virus (HIV) and Cryptosporidium parvum. Therefore, we evaluated its antimalarial effects on Plasmodium falciparum and Plasmodium berghei. In vitro, chloroquine (CQ)-sensitive and resistant strains of P. falciparum parasitized red blood cells were incubated with escalating doses of alpha-epi-Br or CQ. In vivo, 62 rats were infected with P. berghei and treated with CQ or alpha-epi-Br. At the highest doses tested against a CQ-sensitive strain, parasitemias decreased from 25.4% in the saline control group to 4.3% and 4.8% in the alpha-epi-Br and CQ groups, respectively (P < 0.05). Against two CQ-resistant strains, parasitemias decreased from 22.3-28.8% and 24.8-30% in the CQ and saline groups, respectively, to 2.5-2.7% in the alpha-epi-Br groups (P = 0.003). In vivo, on Day 4, parasitemias decreased from 23% in the saline group to 9-12% and 12% in the in alpha-epi-Br and CQ groups, respectively (P < 0.05). These data demonstrate that alpha-epi-Br shows activity against CQ-sensitive and resistant strains of P. falciparum in vitro. At the doses tested against P. berghei in vivo in rats, alpha-epi-Br is comparable to CQ.

Psoralen photochemotherapy (PUVA) and pregnancy.

BACKGROUND AND DESIGN: Psoralen photochemotherapy (PUVA) may carry a risk of mutagenesis and teratogenesis. Using a medical birth registry and other health registries, infants born to women who had been treated with PUVA were identified. Exposure information was obtained from treating hospitals and from the license-granting agency. A total of 504 infants were born of pregnancies occurring after PUVA treatment, and 689 infants were born of pregnancies occurring before such treatment. In another 14 cases, treatment occurred during pregnancy. RESULTS: No increase in infant or child mortality or in the presence of congenital malformations could be seen after PUVA treatment. There was a marked increase in low-birth-weight infants when pregnancy occurred after treatment, and this is probably not explained by maternal smoking, but could be an effect of the underlying disease. CONCLUSIONS: The theoretical mutagenic and teratogenic effect of PUVA treatment apparently does not carry any significant risk for abnormal delivery outcome.

Maternal carbamazepine and infant spina bifida.

Women with epilepsy giving birth during 1973 to 1991 were identified by record linkage of Swedish health registries. Among 3,625 identified infants, 9 had spina bifida. A nested case-control study was performed, comparing drugs used in early pregnancy in the 9 cases and in 18 controls, matched for year of delivery, maternal age, and parity. Six of the spina bifida mothers had used carbamazepine and two had used valproic acid. Among the controls, 5 women used carbamazepine and one valproic acid. There is an apparent excess risk for spina bifida after use of either of these two drugs, but it is not statistically significant when the analysis is restricted to drug-using women. The findings support earlier reports in the literature of an association between carbamazepine and spina bifida.

Drug intoxication during pregnancy: a study with central registries.

By linking two health registries, one on all infants born and one on hospital discharges, 424 infants were identified born after pregnancies when the mothers had been hospitalized for an intoxication, mainly with drugs. In 126 infants, exposure had occurred during the organ forming period, 99 of them because of suicidal or accidental overdosage of drugs; 70 of these were psychoactive drugs. None of the 70 infants had a congenital malformation, but the upper 95% confidence limit includes a 10% risk increase. An effect on low birth weight rate was seen only after drug complications following medical treatments during weeks 12 to 30. The study supports an earlier study from Hungary that reported that drug intoxication during pregnancy does not carry a substantial teratogenic risk.

Cell cycle time, growth fraction and cell loss in xenografted head and neck cancer.

In a previous cell kinetic study with DNA flow cytometry (FCM) on xenografted human squamous cell carcinoma of the head and neck (HNSCC), there were significant variations in cell cycle phase distribution during early growth of the transplanted tumors. The object of the present study was to investigate further the cell kinetic mechanisms associated with variation in the growth rate of HNSCC. Xenografts from the same tumor line were examined on three different occasions: 12, 25 and 36 days following transplantation into nude mice. Cell cycle time "Tc", tumor growth fraction (GF) and cell loss factor were determined by computerized curve-fit analysis from percentage labelled mitoses curves. The mean growth curve of the tumors was logistic, with tumor doubling time (Td) ranging from 7.39 days to 8.86 days, and increasing as tumor volume increased. Although growth rate was higher in younger tumors, the cell cycle was longer with a median "Tc" of 69 hours on day 12 versus 34 hours on day 36. There were only minor variations in cell cycle phase distribution as measured by FCM. The growth fraction decreased slightly from 80% to 69% between day 12 and day 36, whereas cell loss factor increased markedly from 49% on day 12 to 78% on day 36. The results of the study emphasize the fact that cell loss is one of the most important cell kinetic determinants of tumor growth rate. This should be borne in mind when calculating proliferative cell kinetics in HNSCC.

Infant mortality in Denmark and Sweden. A comparison based on data in two national registries.

OBJECTIVES: To study in detail the differences in infant mortality between Denmark and Sweden. STUDY DESIGN: Data retrieved from national health registers on infant death rates were compared for 1980-1988, supplemented with a study on the impact of socio-economic conditions in 1985-86 (Denmark) or 1986 (Sweden). RESULTS: Even after stratification for maternal age, parity, and socio-economic group, the Danish mortality rate was higher in all age-at-death intervals except for stillbirths. Maternal age-parity distribution was more favourable in Denmark, the socio-economic distribution in Sweden. The most marked country differences was seen in young women. The difference in the rate of perinatal deaths but not of later deaths is explainable by a more favourable birth weight distribution in Sweden than in Denmark. CONCLUSIONS: The studied variables do not explain the difference in mortality risk but it may be due to life style factors so far not identified.

Canines as sentinels for Lyme disease in San Diego County, California.

Prevalence of Lyme borreliosis in canine sentinels has been shown to correlate with infection in humans. One thousand canine sera (917 dogs, 83 coyotes) obtained from animal control authorities and area veterinarians were screened by ELISA for antibodies to Borrelia burgdorferi. Results were validated by Western blot and indirect fluorescent antibody (IFA) tests at referee laboratories. Criterion for a positive Western blot was presence of 5 of 10 of the most common antigen IgG bands; for IFA, >1:128 or the equivalent when correcting for interlaboratory variability. Twenty-two of 1,000 canines were confirmed serologically positive (21 dogs and 1 coyote; seroprevalence 2.3% and 1.2%, respectively). Lifestyle, breed size, gender, and age were not statistically predictive of seropositive status. No regional clustering of seropositive animals was detected. The low prevalence of seropositivity in sentinel canines suggests the Lyme borreliosis hazard in San Diego County is minimal.

Twin births to mothers who are twins: a registry based study.

OBJECTIVES: To estimate the risk of having twin infants for mothers who are twins; to investigate the genetic influence on twinning. DESIGN: Retrospective study of multiple births in two nationwide registries. SETTING: Sweden. SUBJECTS: Multiple births among 31,586 deliveries between 1973 and 1991 to women who were twins. MAIN OUTCOME MEASURES: Numbers of monozygotic and dizygotic twin births expected and estimated. RESULTS: Women who are dizygotic twins have a moderately increased risk of having twins (relative risk 1.30, 95% confidence interval 1.14 to 1.49) which seems to be completely the result of dizygotic twinning. When a mother is a monozygotic twin, her risk of having twins of the same sex is significantly increased (1.47; 1.10 to 1.97). This is the result of an excess of monozygotic twins (39 pairs estimated, 18 expected). CONCLUSIONS: Women who are twins have an increased risk of giving birth to twins. Genetic components of monozygotic and dizygotic twinning seem to be independent.

On the history and definition of Preiser's disease.

In 1910, Georg Preiser (1876-1913) described five cases of rarifying osteitis. Based on his imaging studies, he diagnosed post-traumatic avascular necrosis (AVN) of the scaphoid without any sign of primary fracture. This was followed by an article in 1911 in which Preiser related his findings to Kienböck's disease and Köhler's disease of the tarsal navicular. Upon searching the literature, we found descriptions and discussions of Preiser's imaging; however, the original images have never been published. We reproduce Preiser's original imaging in this current review. All of these appear to show a fracture and no signs of AVN, suggesting that Georg Preiser misinterpreted his findings. There is no apparent uniformity in the literature regarding the definition, description, or aetiology of Preiser's disease, and it is for this reason that we find the use of eponyms to be confusing.

Is there an increased risk for drug treated attention deficit/hyperactivity disorder in children born after in vitro fertilization?

BACKGROUND: There is mounting evidence that children born after in vitro fertilization (IVF) run an increased risk of neurological complications and notably cerebral palsy. Whether developmental disturbances occur more often than expected is debated. AIM: To investigate the risk for ADHD in children conceived after IVF. METHODS: Children conceived after IVF and born between 1982 and 2005 were identified from all IVF clinics in Sweden. Children who developed attention deficit/hyperactivity disorder (ADHD) were identified with the use of a register over all prescribed drugs in Sweden, using prescriptions for methylphenidate or atomixetine as indicators of ADHD. Maternal and neonatal characteristics were obtained by linkage with the Medical Birth Register and relevant confounders were adjusted for using Mantel-Haenszel procedures. We studied 28 158 children born after IVF and compared them with 2 417 886 children in the population. RESULTS: After adjustment for year of birth, maternal age, parity, smoking, BMI, and maternal education and after exclusion of women who did not cohabit, a weak but statistically significant association was found with an odds ratio=1.18, 95% confidence interval 1.03-1.36. The effect was stronger in girls (OR=1.40) than boys (OR=1.11) but this difference could be random. After adjustment for length of involuntary childlessness, the OR decreased slightly and lost statistical significance. CONCLUSIONS: The study suggests a weak association between IVF and drug treated ADHD.

Cerebral palsy in children born after in vitro fertilization. Is the risk decreasing?

BACKGROUND: Infants born after in vitro fertilization (IVF) differ from spontaneously conceived infants in a number of aspects which could increase the risk for future cerebral palsy (CP), e.g., multiple births, preterm births, neonatal complications. AIMS: To follow up children conceived by IVF with respect to risk for CP. METHODS: Infants born after IVF were identified from all IVF clinics in Sweden 1982-2007. Perinatal characteristics were obtained by linkage with the Medical Birth Register. The presence of CP in children born after IVF and in other children was identified from the Patient Register which contains diagnoses given at hospitalizations or specialist outpatient clinics. The risk for CP after IVF was studied after adjustment for year of birth, maternal age, parity, and smoking, all factors which co-vary both with IVF and with CP. Stratification was made for singletons and multiple births and for various neonatal outcomes. RESULTS: The adjusted odds ratio for CP after IVF was 1.81 (95% confidence interval, 95% CI 1.52-2.13), lower and not statistically significant when singletons or when unlike-sexed twins were analyzed. Stratification for various neonatal characteristics also reduced odds ratios to non-significant levels. For the last few years of the study (2004-2007) when the twinning rate after IVF was <10%, the odds ratio for CP was 0.97 (95% CI 0.57-1.66). CONCLUSIONS: The moderately increased risk for CP was most likely a consequence of an increased risk of neonatal morbidity, notably associated with multiple births.

In search of a rational approach to chronic kidney disease detection and management.

Rates of incident end-stage renal disease persist above established goals, driving efforts for early identification of chronic kidney disease (CKD) to reduce progression. The detection of CKD using existing electronic data sources has been proposed as an efficient identification method; however, this method is not without potential challenges and limitations.