Hypophosphatemia after high-dose iron repletion with ferric carboxymaltose and ferric derisomaltose-the randomized controlled HOMe aFers study.

BACKGROUND: In patients with iron deficiency anemia, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) allow high-dose iron repletion. While FCM is reported to induce hypophosphatemia, the frequency of hypophosphatemia after an equivalent dosage of FDI had not been assessed prospectively. METHODS: In the prospective, single-center, double-blind HOMe aFers study, 26 women with iron deficiency anemia (hemoglobin < 12 g/dL plus either plasma ferritin ≤ 100 ng/mL or a plasma ferritin ≤ 300 ng/mL and transferrin saturation (TSAT) ≤ 30%) were randomized to a single intravenous infusion of 20 mg/kg body weight (up to a maximum of 1000 mg) FCM or FDI. The primary endpoint was the incidence of hypophosphatemia (plasma phosphorus levels < 2.0 mg/dL at day 1, day 7 ± 2, and/or day 35 ± 2 after the infusion). In order to investigate potential skeletal and cardiovascular implications, we assessed changes in other components of mineral and bone metabolism, left ventricular function, and arrhythmias. RESULTS: Hypophosphatemia occurred more frequently in women treated with FCM (9 out of 12 [75%]) than in those treated with FDI (1 out of 13 [8%]; p = 0.001). Within 24 h after iron supplementation, women in the FCM group had significant higher plasma intact FGF23 (p < 0.001) and lower plasma 1.25-dihydroxyvitamin D (p < 0.001). As an indicator of urinary phosphorus losses, urinary fractional phosphorus excretion was higher in the FCM group (p = 0.021 at day 7 ± 2 after iron supplementation). We did not observe differences in skeletal and cardiovascular markers, potentially because of the limited number of participants. CONCLUSIONS: While both FCM and FDI provide efficient iron repletion in participants with iron deficiency anemia, FCM induced hypophosphatemia more often than FDI. TRIAL REGISTRATION: Clinical Trials.gov NCT02905539. Registered on 8 September 2016. 2015-004808-36 (EudraCT Number) U1111-1176-4563 (WHO Universal Trial Number) DRKS00010766 (Deutsches Register Klinischer Studien).

Fatal outcomes in family transmission of Mycoplasma pneumoniae.

BACKGROUND: Mycoplasma pneumoniae continues to be a significant cause of community-acquired pneumonia and, on rare occasions, manifests as fulminant disease that leads to mortality, even in healthy individuals. METHODS: We conducted a retrospective study on members of a family who were quarantined by the Centers for Disease Control and Prevention in 2002 for respiratory failure and death of a 15-year-old brother (sibling 1) and a 13-year-old sister (sibling 2). Collected airway, cerebrospinal fluid (CSF), and serum samples from both deceased siblings and serum samples from both parents and the remaining 3 ill siblings (sibling 3-5) were tested using a range of diagnostic assays. Autopsy lung tissue samples from sibling 2 were also assessed using immunohistochemical and immunoelectron microscopic methods. RESULTS: Autopsy evaluation of sibling 1 revealed cerebral edema consistent with hypoxic ischemic encepatholopathy and pulmonary findings of bronchiolitis obliterans with organizing pneumonia (BOOP). Postmortem lung examination of sibling 2 revealed lymphoplasmacytic bronchiolitis with intraluminal purulent exudate, BOOP, and pulmonary edema. Results of diagnostic assays implicated the household transmission of M. pneumoniae among all 5 siblings and both parents. Further analysis of lung tissue from sibling 2 demonstrated the presence of M. pneumoniae organisms and community-acquired respiratory distress syndrome toxin. M. pneumoniae was cultured directly from sibling 2 autopsy lung tissue. CONCLUSION: Evidence is provided that M. pneumoniae was readily transmitted to all members of the household and that the resulting infections led to a spectrum of individual responses with variation in disease progression, including lymphoplasmacytic bronchiolitis, BOOP, and death.

Prevalence of nosocomial infections in neonatal intensive care unit patients: Results from the first national point-prevalence survey.

OBJECTIVES: Patients admitted to neonatal intensive care units (NICUs) are at high risk of nosocomial infection. We conducted a national multicenter assessment of nosocomial infections in NICUs to determine the prevalence of infections, describe associated risk factors, and help focus prevention efforts. STUDY DESIGN: We conducted a point prevalence survey of nosocomial infections in 29 Pediatric Prevention Network NICUs. Patients present on the survey date were included. Data were collected on underlying diagnoses, therapeutic interventions/treatments, infections, and outcomes. RESULTS: Of the 827 patients surveyed, 94 (11.4%) had 116 NICU-acquired infections: bloodstream (52.6%), lower respiratory tract (12.9%), ear-nose-throat (8.6%), or urinary tract infections (8.6%). Infants with infections were of significantly lower birth weight (median 1006 g [range 441 to 4460 g] vs 1589 g [range 326 to 5480 g]; P <.001) and had longer median durations of stay than those without infections (88 days [range 8 to 279 days] vs 32 days [range 1 to 483 days]; P <.001). Most common pathogens were coagulase-negative staphylococci and enterococci. Patients with central intravascular catheters (relative risk = 3.81, CI 2.32-6.25; P <.001) or receiving total parenteral nutrition (relative risk = 5.72, CI 3.45-9.49; P <.001) were at greater risk of bloodstream infection. CONCLUSIONS: This study documents the high prevalence of nosocomial infections in patients in NICUs and the urgent need for more effective prevention interventions.

Reality check: how should we control antimicrobial use? Current practices and controversies.

The infectious diseases community shares a wide consensus about the need for control of antimicrobial use. However, current practices toward this goal remain controversial. This "Reality Check" session assessed attendees of the 4th Decennial Conference regarding their knowledge and practices about control of antimicrobial use in hospitals.

Prophylaxis for neonatal group B streptococcus infections.

For the past two decades, group B streptococcus (GBS) has been the pathogen most frequently isolated from neonates with invasive bacterial disease. This is a review of the relevant aspects of microbiology, epidemiology, and clinical manifestations and a summary of the major studies of prevention strategies that led to the development of the 1996 consensus guidelines for prevention of perinatal GBS disease. There is now sufficient experience to know that > or = 80% of cases of early onset GBS disease can be prevented when a protocol for intrapartum chemoprophylaxis with either penicillin or ampicillin is implemented consistently within a delivery population. Present controversies revolve around the choice between a universal screening-based strategy versus a risk factor-based strategy, optimal management of the neonate born to a mother who received intrapartum antimicrobial prophylaxis, and effective methods to ensure implementation. The present guidelines will likely be refined as additional experience is gained.

Prevention of early-onset group B streptococcal disease: another look at single-dose penicillin at birth.

OBJECTIVE: To determine the effect of single-dose penicillin given at birth on the rate of early-onset group B streptococcal (GBS) invasive disease in an inner-city population. METHODS: Laboratory-based surveillance of GBS disease from 1972-1994 at Parkland Memorial Hospital and Children's Medical Center in Dallas, Texas, was reviewed retrospectively. All infants born at Parkland Memorial Hospital from January 1, 1972 to December 31, 1994, or a total of 259,049 live births, were included. Early-onset (within 3 days) GBS disease rates were compared for each of five observation groups to determine the efficacy of a single dose of aqueous penicillin G 50,000 U for infants weighing 2,000 g or more and 25,000 U for those weighing less than 2,000 g) administered intramuscularly within 1 hour of delivery for prevention of GBS disease. RESULTS: The rates of early-onset GBS disease were compared in five observation groups: A) pre-study, January 1, 1972 to December 3, 1977--no GBS prophylaxis; B) prospective, controlled intervention study, December 4, 1977 to May 31, 1981, including infants who received a single dose of penicillin at birth (group B1) and those who did not (group B2); C) universal penicillin prophylaxis, June 1, 1981 to October 31, 1986; and D) no routine penicillin prophylaxis, November 1, 1986 to December 31, 1994. The incidence of early-onset GBS disease in the penicillin groups (B1, C) was significantly lower than that in the untreated groups (A, B2, D): 0.25 and 0.63 per 1,000 versus 1.59, 1.19, and 1.95 per 1,000, respectively (P < or = .03). The incidence of late-onset GBS disease was unaffected by penicillin prophylaxis, and there was no increase in the incidence of disease caused by penicillin-resistant pathogens or associated mortality in penicillin-treated infants; 2.2 and 2.1 per 1,000 versus 1.6 and 3.3 per 1,000 for disease; 1.0 and 0.5 per 1,000 versus 0.4 and 0.3 per 1,000 for deaths. CONCLUSION: Universal administration of single-dose penicillin at birth is a safe and effective intervention for the prevention of early-onset GBS disease.

Eradication of endemic methicillin-resistant Staphylococcus aureus infections from a neonatal intensive care unit.

To control infections with endemic methicillin-resistant Staphylococcus aureus (MRSA) in a neonatal intensive care unit (NICU), triple dye was applied to the umbilical cords of infants in the intermediate-care but not the intensive-care area. The rate of MRSA infection, adjusted for time and intensity of care, decreased in the intermediate-care area (rate ratio, 0.35; 95% confidence interval [CI], 0.14-0.87; P < .01) but not in the intensive-care area (rate ratio, 0.92; 95% CI, 0.41-2.24; P = .48). After 22 months, the rate increased in both areas (Mantel-Haenszel rate ratio, 1.7; 95% CI, 1.0-2.8; P < .05) after overcrowding and understaffing increased. After temporary reduction of overcrowding and understaffing, extension of triple dye use to the intensive-care area and dedication of an infection control nurse to the NICU, MRSA colonization and infection rates decreased to near zero in both areas (infection rate ratios, 0.09 and 0.11, respectively; P < .005). The endemic MRSA strain, identified by pulsed-field gel electrophoresis, was eradicated.

Parasitic infections of the central nervous system in children. Part I: Congenital infections and meningoencephalitis.

This review article presents the epidemiology, pathogenesis, clinical presentation, laboratory and radiologic findings, and treatment of parasitic infections of the central nervous system in children. Some obscure parasitic infections are included. To assist the clinician faced with a specific case, infections are categorized first by predominant clinical manifestations: congenital disease, meningoencephalitis, focal lesions, and disseminated multisystem disease. Within the clinical categories, parasites are grouped according to the geographic area where most human infections occur. Congenital infections and those that present most frequently as meningoencephalitis are discussed in this part of the review.

Subacute measles encephalitis in the young immunocompromised host: report of two cases diagnosed by polymerase chain reaction and treated with ribavirin and review of the literature.

Two young patients with subacute measles encephalitis are described: a 20-year-old male hemophiliac infected with human immunodeficiency virus (HIV) and a 4-year-old girl with acute leukemia. Both patients were afebrile and had persistent focal seizures and slurred speech beginning 2 and 7 months, respectively, after the onset of uncomplicated acute measles. The diagnosis of subacute measles encephalitis was established by demonstration of paramyxovirus nucleocapsid on electron microscopy of brain tissue in one case and by detection of measles virus genome with the polymerase chain reaction in both. Treatment of the HIV-infected man with intravenous ribavirin was begun when the patient lost consciousness after several weeks of seizures; he died. The girl with leukemia was treated early after the onset of symptoms and recovered after a 15-week course. Review of 31 previously published cases revealed a typical clinical presentation. Cerebrospinal fluid (CSF) analysis, electroencephalography, measurement of measles antibody in serum and CSF, and computed tomography of the brain were not helpful in the diagnosis of subacute measles encephalitis. In contrast, histologic examination of brain tissue proved useful in establishing the diagnosis. On the basis of our experience and our literature review, we conclude that histologic and polymerase chain reaction studies of brain tissue are required for the early diagnosis of subacute measles encephalitis and that therapy with intravenous ribavirin is effective when administered early.

Infections and pseudoinfections due to povidone-iodine solution contaminated with Pseudomonas cepacia.

In 1989 we investigated the first instance of Pseudomonas cepacia infections due to intrinsic contamination of a povidone-iodine product. Six patients in a Texas pediatric facility had P. cepacia infection or pseudoinfection (three, peritonitis; one, pseudoperitonitis; and two, pseudobacteremia). Epidemiological studies showed one risk factor for infection of peritoneal fluid with P. cepacia: performance of peritoneal dialysis in the dialysis unit with use of one lot of povidone-iodine later found to be intrinsically contaminated (4/5 vs. 0/16, P = .001). Blood cultures yielded P. cepacia after nurses wiped the tops of blood culture bottles with the povidone-iodine solution before inoculation. P. cepacia was cultured from three povidone-iodine containers used at the hospital and from four containers of the same lot obtained from other health-care facilities in Texas and California. Isolates from patients and the povidone-iodine had similar antibiograms, identical plasmid profiles, and identical DNA banding patterns on the basis of results of ribonucleotide typing. This investigation demonstrates that intrinsic contamination of povidone-iodine solution with P. cepacia can result in infections in addition to colonization and/or pseudoinfection.

Significance of a positive urine group B streptococcal latex agglutination test in neonates.

We assessed the clinical significance of a reactive urine latex agglutination (LA) test in neonates without bacteriologically confirmed group B streptococcal (GBS) infection. In a retrospective review of a 3 1/2-month period, during which 367 urine specimens from newborn infants evaluated for suspected sepsis were tested by LA, 25 infants (6.9%) with sterile blood cultures but positive urine LA test results were compared with a control group of 112 infants with both blood cultures and urine LA test results negative for GBS. When the data were studied with stepwise discriminant analysis, the only variables significantly associated with a positive urine LA test result were immature to total neutrophil ratios greater than or equal to 0.16 at 0 and 12 hours. The influence of mucosal GBS colonization on urine LA test results was then investigated prospectively in 98 healthy infants (83 born to mothers colonized with GBS and 15 born to mothers with negative GBS cultures). Eight (8.2%) of the infants studied, or 8 of 52 (15.4%) infants colonized with GBS, had a positive urine LA test result. GBS was isolated from urine cultures of all infants with a positive urine LA test result. A positive urine LA test result was associated with positive GBS rectal and vaginal cultures and with increased density of colonization at those sites. We conclude that contamination of bag specimens of urine with GBS from perineal and rectal colonization may produce a positive urine LA test result in an infant with no systemic sign of infection.

Infectious complications of craniofacial surgery in children.

During the 10-year period 1975 through 1984, 219 children with congenital anomalies underwent oromaxillary or craniofacial surgery at Children's Medical Center, Dallas. There were no infectious complications following 56 oromaxillary procedures. The overall rate of infection following craniofacial surgery was 14.7% (24 of 163). Infection rates were significantly increased when a combined (monoblock) repair was performed (45% [15 of 33]), compared with either intracranial (8% [six of 72]) or extracranial (5% [three of 58]) procedures alone (P less than .001). The variables identified by multivariate discriminant analysis as useful independent predictors of postoperative infection were, in order of decreasing importance: length of operation, type of procedure (intracranial, extracranial, or combined), and age. Staged procedures are recommended for craniofacial surgery whenever possible because of the significant increase in rate of infection associated with the monoblock repair.

Computerized diagnosis: implications for clinical education.

The advent of the small computer as a basic clinical tool will have a significant impact on clinical practice and medical training. The application of probability theory to clinical diagnosis has led to the development of several practical diagnostic programs which run on small computers. Expert systems--interactive programs which function as 'electronic consultants'--have now been successfully developed for a number of clinical situations. Experience with two of these, INTERNIST/CADUCEUS and MYCIN, has provided insight into problems and prospects for expert systems in medicine. Less complex programs, particularly those employing clinical prediction rules, and expert system shells, seem well suited for clinical environments. Although computerized medical diagnosis holds great promise as an aid to clinicians, its success will largely be determined by the quality of the information that clinicians provide for analysis. A brief review of the status of bedside diagnosis reveals that data-gathering strategies and techniques must be better understood. In order to take full advantage of computer programs for diagnosis, basic diagnostic skills must be more heavily emphasized in clinical training.