Michael M. McNeil

Trends in Mortality Due to Invasive Mycotic Diseases in the United States, 1980–1997

To determine national trends in mortality due to invasive mycoses, we analyzed National Center for Health Statistics multiple-cause-of-death record tapes for the years 1980 through 1997, with use of their specific codes in the International Classification of Diseases, Ninth Revision (ICD-9 codes 112.4-118 and 136.3). In the United States, of deaths in which an infectious disease was the underlying cause, those due to mycoses increased from the tenth most common in 1980 to the seventh most common in 1997. From 1980 through 1997, the annual number of deaths in which an invasive mycosis was listed on the death certificate (multiple-cause [MC] mortality) increased from 1557 to 6534. In addition, rates of MC mortality for the different mycoses varied markedly according to human immunodeficiency virus (HIV) status but were consistently higher among males, blacks, and persons > or =65 years of age. These data highlight the public health importance of mycotic diseases and emphasize the need for continuing surveillance.

POSTOPERATIVE INFECTIONS TRACED TO CONTAMINATION OF AN INTRAVENOUS ANESTHETIC, PROPOFOL

BACKGROUND Between June 1990 and February 1993, the Centers for Disease Control and Prevention conducted investigations at seven hospitals because of unusual outbreaks of bloodstream infections, surgical-site infections, and acute febrile episodes after surgical procedures. METHODS We conducted case-control or cohort studies, or both, to identify risk factors. A case patient was defined as any patient who had an organism-specific infection or acute febrile episode after a surgical procedure during the study period in that hospital. The investigations also included reviews of procedures, cultures, and microbiologic studies of infecting, contaminating, and colonizing strains. RESULTS Sixty-two case patients were identified, 49 (79 percent) of whom underwent surgery during an epidemic period. Postoperative complications were more frequent during the epidemic period than before it. Only exposure to propofol, a lipid-based anesthetic agent, was significantly associated with the postoperative complications at all seven hospitals. In six of the outbreaks, an etiologic agent (Staphylococcus aureus, Candida albicans, Moraxella osloensis, Enterobacter agglomerans, or Serratia marcescens) was identified, and the same strains were isolated from the case patients. Although cultures of unopened containers of propofol were negative, at two hospitals cultures of propofol from syringes currently in use were positive. At one hospital, the recovered organism was identical to the organism isolated from the case patients. Interviews with and observation of anesthesiology personnel documented a wide variety of lapses in aseptic techniques. CONCLUSIONS With the increasing use of lipid-based medications, which support rapid bacterial growth at room temperature, strict aseptic techniques are essential during the handling of these agents to prevent extrinsic contamination and dangerous infectious complications.

Adverse events following influenza A (H1N1) 2009 monovalent vaccines reported to the Vaccine Adverse Event Reporting System, United States, October 1, 2009-January 31, 2010.

The United States (US) influenza A (H1N1) 2009 monovalent (2009-H1N1) vaccination program began in October 2009. Reports to the vaccine adverse event reporting system (VAERS), a US spontaneous reporting system, were reviewed to identify potential rare events or unusual adverse event (AE) patterns after 2009-H1N1 vaccination. The adverse event profile after 2009-H1N1 vaccine in VAERS (∼10,000 reports) was consistent with that of seasonal influenza vaccines, although the reporting rate was higher after 2009-H1N1 than seasonal influenza vaccines, this may be, at least in part, a reflection of stimulated reporting. Death, Guillain-Barré syndrome and anaphylaxis reports after 2009-H1N1 vaccination were rare (each <2 per million doses administered).

Effects of a Reduced Dose Schedule and Intramuscular Administration of Anthrax Vaccine Adsorbed on Immunogenicity and Safety at 7 Months: A Randomized Trial

CONTEXT In 1999, the US Congress directed the Centers for Disease Control and Prevention to conduct a pivotal safety and efficacy study of anthrax vaccine adsorbed (AVA). OBJECTIVE To determine the effects on serological responses and injection site adverse events (AEs) resulting from changing the route of administration of AVA from subcutaneous (s.q.) to intramuscular (i.m.) and omitting the week 2 dose from the licensed schedule. DESIGN, SETTING, AND PARTICIPANTS Assessment of the first 1005 enrollees in a multisite, randomized, double-blind, noninferiority, phase 4 human clinical trial (ongoing from May 2002). INTERVENTION Healthy adults received AVA by the s.q. (reference group) or i.m. route at 0, 2, and 4 weeks and 6 months (4-SQ or 4-IM; n = 165-170 per group) or at a reduced 3-dose schedule (3-IM; n = 501). A control group (n = 169) received saline injections at the same time intervals. MAIN OUTCOME MEASURES Noninferiority at week 8 and month 7 of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer (GMT), and proportion of responders with a 4-fold rise in titer (%4 x R). Reactogenicity outcomes were proportions of injection site and systemic AEs. RESULTS At week 8, the 4-IM group (GMC, 90.8 microg/mL; GMT, 1114.8; %4 x R, 97.7) was noninferior to the 4-SQ group (GMC, 105.1 microg/mL; GMT, 1315.4; %4 x R, 98.8) for all 3 primary end points. The 3-IM group was noninferior for only the %4 x R (GMC, 52.2 microg/mL; GMT, 650.6; %4 x R, 94.4). At month 7, all groups were noninferior to the licensed regimen for all end points. Solicited injection site AEs assessed during examinations occurred at lower proportions in the 4-IM group compared with 4-SQ. The odds ratio for ordinal end point pain reported immediately after injection was reduced by 50% for the 4-IM vs 4-SQ groups (P < .001). Route of administration did not significantly influence the occurrence of systemic AEs. CONCLUSIONS The 4-IM and 3-IM regimens of AVA provided noninferior immunological priming by month 7 when compared with the 4-SQ licensed regimen. Intramuscular administration significantly reduced the occurrence of injection site AEs. Trial Registration clinicaltrials.gov Identifier: NCT00119067.

Nosocomial Malassezia pachydermatis bloodstream infections in a neonatal intensive care unit

Malassezia pachydermatis, a lipophilic yeast, has been described to cause sporadic nosocomial bloodstream infections (BSI). Nosocomial outbreaks of M. pachydermatis BSI have never been described. A cluster of M. pachydermatis BSIs in the neonatal intensive care unit at Louisiana State University Medical Center, University Hospital provided the opportunity to investigate the epidemiology of this organism and apply molecular epidemiologic typing techniques. A case-patient was defined as any neonatal intensive care unit patient in University Hospital with a blood culture positive for M. pachydermatis from January 1, 1989, through August 15, 1991. Five patients met the case definition. Case-patients were premature as estimated by gestational age and required prolonged hospitalization. Case-patients received parenteral nutrition and intravenous lipids for twice as many days as randomly selected controls. No environmental source of M. pachydermatis was identified; however, infants on each side of a previously identified M. pachydermatis-colonized infant became colonized with M. pachydermatis during a 20-day period. Chromosomal analysis of five M. pachydermatis blood isolates from two case-patients had identical banding patterns. These data show that M. pachydermatis can cause nosocomial BSI outbreaks, that premature infants receiving parenteral nutrition and/or lipids may be at greatest risk and that transmission is most likely from person to person, probably via the hands of medical personnel.

Candida parapsilosis bloodstream infections in neonatal intensive care unit patients : epidemiologic and laboratory confirmation of a common source outbreak

BACKGROUND Candida parapsilosis is a common cause of sporadic and epidemic infections in neonatal intensive care units (NICUs). When a cluster of C. parapsilosis bloodstream infections occurred in NICU patients in a hospital in Louisiana, it provided us with the opportunity to conduct an epidemiologic investigation and to apply newly developed molecular typing techniques. METHODS A case-patient was defined as any NICU patient at Louisiana State University Medical Center, University Hospital, with a blood culture positive for C. parapsilosis during July 20 to 27, 1991. To identify risk factors for C. parapsilosis bloodstream infection, a cohort study of all NICU infants admitted during July 17 to 27, 1991, was performed. Electrophoretic karyotyping was used to assess the relatedness of C. parapsilosis isolates. RESULTS The receipt of liquid glycerin given as a suppository was identified as a risk factor (relative risk, 31.2; 95% confidence intervals, 4.3 to 226.8). Glycerin was supplied to the NICU in a 16-oz multidose bottle. Bottles used at the time of the outbreak were not available for culture. All six available isolates from four case-patients had identical chromosomal banding patterns; six University Hospital non-outbreak isolates had different banding patterns. CONCLUSIONS This study demonstrates the utility of combined epidemiologic and laboratory techniques in identifying a novel common source for a C. parapsilosis bloodstream infection outbreak and illustrates that extreme caution should be exercised when using multidose medications in more than one patient.

The Vaccine Safety Datalink: successes and challenges monitoring vaccine safety

The Vaccine Safety Datalink (VSD) is a collaborative project between the Centers for Disease Control and Prevention (CDC) and 9 health care organizations. Established in 1990, VSD is a vital resource informing policy makers and the public about the safety of vaccines used in the United States. Large linked databases are used to identify and evaluate adverse events in over 9 million individuals annually. VSD generates rapid, important safety assessments for both routine vaccinations and emergency vaccination campaigns. VSD monitors safety of seasonal influenza vaccines in near-real time, and provided essential information on the safety of influenza A (H1N1) 2009 monovalent vaccine during the recent pandemic. VSD investigators have published important studies demonstrating that childhood vaccines are not associated with autism or other developmental disabilities. VSD prioritizes evaluation of new vaccines; searches for possible unusual health events after vaccination; monitors vaccine safety in pregnant women; and has pioneered development of biostatistical research methods.

Mycobacterium septicum sp. nov., a new rapidly growing species associated with catheter-related bacteraemia.

Rapidly growing mycobacteria are capable of causing several clinical diseases in both immunosuppressed and immunocompetent individuals. A previously unidentified, rapidly growing mycobacterium was determined to be the causative agent of central line sepsis in a child with underlying metastatic hepatoblastoma. Four isolates of this mycobacterium, three from blood and one from the central venous catheter tip, were studied. Phenotypic characterization, HPLC and genetic analysis revealed that while this organism most closely resembled members of the Mycobacterium fortuitum complex and Mycobacterium senegalense, it differed from all previously described species. Phenotypic tests useful in differentiating this species from similar rapidly growing mycobacteria included: growth at 42 degrees C, hydrolysis of acetamide, utilization of citrate, production of arylsulfatase (3-d), acidification of D-mannitol and i-myo-inositol, and susceptibility to erythromycin, vancomycin and tobramycin. The name Mycobacterium septicum is proposed for this new species. The type strain has been deposited in Deutsche Sammlung von Mikroorganismen und Zellkulturen as DSM 44393T and in the American Type Culture Collection as strain ATCC 700731T.

Microbial Growth and Endotoxin Production in the Intravenous Anesthetic Propofol

OBJECTIVE In this study, we measured microbial growth and endotoxin production in the intravenous anesthetic propofol using 10 different microbial strains; 6 isolated from outbreak cases and 4 from laboratory stock cultures. DESIGN In each trial, endotoxin-free glass tubes containing 10 ml propofol were inoculated with 10(0)-10(3) CFU/ml of the test organism and incubated at 30 degrees C for 72 hours. SETTING In May and June 1990, the Centers for Disease Control received reports of 5 outbreaks in 5 states of postsurgical patient infections and/or pyrogenic reactions. Epidemiologic and laboratory investigations implicated extrinsic contamination of an intravenous anesthetic, propofol, as the probable source of these outbreaks. RESULTS After 24 hours, 9 of the 10 cultures increased in viable counts by 3 to 6 logs. At least 1 ng/ml of endotoxin was produced within 24 hours by Escherichia coli, Enterobacter cloacae, and Acinetobacter calcoaceticus subspecies anitratus. CONCLUSIONS Propofol can support rapid microbial growth and endotoxin production. To avoid infectious complications, scrupulous aseptic technique should be used when preparing or administering this anesthetic.

Investigation of an epidemic of invasive aspergillosis: utility of molecular typing with the use of random amplified polymorphic Dna probes

When seven immunocompromised patients developed invasive aspergillosis during construction at a hospital, new methods were performed to compare fungal isolates and a case-control study was conducted to determine risks for infection. Typing of Aspergillus flavus with the use of restriction endonuclease analysis and restriction fragment length polymorphism using random amplified polymorphic DNA reactions to generate DNA probes revealed different patterns between isolates from two patients and a similar pattern among those from one patient, a health care worker, and an environmental source. Case patients were more likely than controls to have longer periods of hospitalization (median, 83 vs. 24 days; P < 0.01), neutropenia (median, 33 vs. 6 days; P < 0.05), and exposure to broad spectrum antimicrobials (median, 56 vs. 15 days; P = 0.08). No patients restricted to protected areas developed aspergillosis. Risk of exposure of immunocompromised patients to opportunistic organisms stirred up by construction activity may be decreased by admitting these patients to protected areas away from construction activity and by restricting traffic from construction sites to these areas. Although typing of A. flavus isolates did not reveal a single type or source of organism responsible for infection, this method may facilitate epidemiologic investigation of possible nosocomial sources and transmission in similar settings.