Impact of severe hematological abnormalities in the outcome of hospitalized patients with influenza virus infection.

Although hematological abnormalities have been described among patients with influenza virus infection, little is known about their impact on the outcome of the patients. The aim of this study was to assess the frequency and clinical impact of severe hematological abnormalities in patients with confirmed influenza virus infection. This was an observational retrospective study including all adult patients with diagnosis of influenza virus infection hospitalized from January to May 2016 in our institution. Influenza virus infection was diagnosed by means of rRT-PCR assay performed on respiratory samples. Poor outcome was defined as a composite endpoint in which at least one of the following criteria had to be fulfilled: (a) respiratory failure, (b) SOFA ≥2, or (c) death. Two hundred thirty-nine patients were included. Applying the HLH-04 criteria for the diagnosis of hemophagocytic syndrome, cytopenias (hemoglobin ≤9 g/dl, platelets <100,000/µl or neutrophils <1,000/µl) were present in 51 patients (21%). Patients with hematological abnormalities showed higher SOFA scores, respiratory failure, septic shock and in-hospital mortality than the remaining patients. The composite endpoint was present in 33.3% in the cytopenias group vs. 13.3% in the group without cytopenias (p=0.001). In a multivariate analysis, variables associated with the composite endpoint were: use of steroids prior to present admission (OR: 0.12; 95% CI: 0.015-0.96, p=0.046), presence of any hematological abnormality (OR: 3.54; 95% CI:1.66-7.51, p= 0.001), and LDH>225 U/l (OR:4.45; CI:1-19.71, p=0.049). Hematological abnormalities are not uncommon among hospitalized patients with influenza virus infection, and they are associated with a poorer outcome.

Comparison of American and European practices in the management of patients with primary immunodeficiencies.

Primary immunodeficiency diseases (PIDs) comprise a heterogeneous group of rare disorders. This study was devised in order to compare management of these diseases in the northern hemisphere, given the variability of practice among clinicians in North America. The members of two international societies for clinical immunologists were asked about their management protocols in relation to their PID practice. An anonymous internet questionnaire, used previously for a survey of the American Academy of Allergy, Asthma and Immunology (AAAAI), was offered to all full members of the European Society for Immunodeficiency (ESID). The replies were analysed in three groups, according to the proportion of PID patients in the practice of each respondent; this resulted in two groups from North America and one from Europe. The 123 responses from ESID members (23·7%) were, in the majority, very similar to those of AAAAI respondents, with > 10% of their practice devoted to primary immunodeficiency. There were major differences between the responses of these two groups and those of the general AAAAI respondents whose clinical practice was composed of < 10% of PID patients. These differences included the routine use of intravenous immunoglobulin therapy (IVIg) for particular types of PIDs, initial levels of IVIg doses, dosing intervals, routine use of prophylactic antibiotics, perceptions of the usefulness of subcutaneous immunoglobulin therapy (SCIg) and of the risk to patients' health of policies adopted by health-care funders. Differences in practice were identified and are discussed in terms of methods of health-care provision, which suggest future studies for ensuring continuation of appropriate levels of immunoglobulin replacement therapies.

Elevation of serum ferritin levels for predicting a poor outcome in hospitalized patients with influenza infection.

OBJECTIVES: There is increasing evidence that ferritin is a key marker of macrophage activation, but its potential role in influenza infection remains unexplored. Our aim was to assess whether hyperferritinaemia (ferritin ≥500 ng/mL) could be a marker of poor prognosis in hospitalized patients with confirmed influenza A infection. METHODS: We prospectively recruited all hospitalized adult patients who tested positive for the influenza A rRT-PCR assay performed on respiratory samples in two consecutive influenza periods (2016-17 and 2017-18). Poor outcome was defined as the presence of at least one of the following: respiratory failure, admission to the intensive care unit, or in-hospital mortality. RESULTS: Among 494 patients, 68 (14%) developed poor outcomes; 112 patients (23%) had hyperferritinaemia (39/68, 57% in the poor-outcome group versus 73/426, 17% in the remaining patients, p < 0.0001). Median serum ferritin levels were significantly higher in the subgroup of patients with poor outcomes (609 ng/mL, range 231-967 versus 217 ng/mL, range 140-394, p < 0.0001). In multivariate analysis, hyperferritinaemia was associated with a five-fold increase in the odds ratio of developing poor outcome. After adjusting for classic influenza risk factors, ferritin remained as a significant predictive factor in all exploratory models. Ferritin levels had a good discriminative capacity with an area under the ROC curve of 0.72 (95% confidence interval (CI) 0.65-0.8, p < 0.001) and an overall diagnostic accuracy for predicting poor outcome of 79.3% (95%CI 75.4-82.7%). CONCLUSIONS: Serum ferritin may discriminate a subgroup of patients with influenza infection who have a higher risk of developing a poor outcome.

High Intraspecific Genetic Diversity of Nocardia brasiliensis, a Pathogen Responsible for Cutaneous Nocardiosis Found in France: Phylogenetic Relationships by Using sod and hsp65 Genes.

This study aims at genetic characterization and phylogenetic relationships of Nocardia brasiliensis focusing by using housekeeping rrs, hsp65, and sodA genes. N. brasiliensis is the species responsible for 80% of cases of actinomycetoma, one form of cutaneous nocardiosis which occurs mainly in tropical regions reaching immunocompetent patients in which the disease can lead to amputation. We analyze 36 indigenous cases of N. brasiliensis that happened in France. Phylogenetic analysis targeting rrs gene showed no robustness at phylogenetic nodes level. However, the use of a concatenation of hsp65 and sodA genes showed that the tested strains surprisingly ranked in 3 well-defined genotypes. Genotypes 2 and 3 were phylogenetically closer to each other and both diverged from genotype 1 sustained by a high bootstrap of 81%. This last genotype hosts all the cases of pulmonary forms (3), the sole cerebral form, and almost all the cases of immunocompromised patients (3 out of 4). Moreover, excepting one of them, all the strains belonging to this group present a susceptibility to imipenem which is not the case in the other genotypes that rarely count among them strains being susceptible to this drug. The haplotype diversity (Hd) of hsp65 (0.927) and sodA (0.885) genes was higher than that of rrs (0.824). For this gene, we obtained 16 polymorphic sites whereas, for hsp65 and sodA genes, up to 27 and 29 were identified, respectively. This study reveals that these two genes have an important genetic discriminatory power for the evaluation of the intraspecies genetic variability of N. brasiliensis and they may be useful for identification purposes at species level. This study also reveals the possible existence of a new species harbored by genotype 1.

Frequency of respiratory syncytial virus in hospitalized infants with lower acute respiratory tract infection in Colombia.

PIP: In Colombia, health workers obtained a nasopharyngeal wash from 103 infants aged less than 12 months hospitalized for acute lower respiratory infection (ALRI) at the General Hospital of Medellin during April 1994 to April 1995 so researchers could determine the frequency of ALRI caused by respiratory syncytial virus (RSV) in hospitalized children. Immunofluorescence detected RSV infection in 43 (41.7%) patients. The presence of the following signs and symptoms allowed a clinical diagnosis of a viral infection: rhinorrhea, prolonged expiration, expiratory wheezing, interstitial infiltrates, and hyperinflation on chest radiographs as well as negative tests for 3 or 4 acute phase reactants. The physicians initiated antibiotic therapy (for 1-3 days) in 12 cases (27.9%) based on acute phase reactant findings who actually had an RSV infection. When the physicians learned that the laboratory confirmed RSV infection, they stopped antibiotic therapy. Antibiotics were continued in 16 (37.2%) other RSV infected infants, all of whom were less than 2 months old, due to mixed pneumonia (viral and bacterial). 39.4% of RSV-infected children whose clinical findings strongly suggested RSV received no antibiotics. None of these children or other ALRI patients with a viral disease suffered complications. They required less hospitalization time--since no further diagnostic tests were needed--than ALRI patients with a bacterial infection. Admissions for both ALRI and RSV infection peaked during November to January. RSV incidence peaked in January (23.3%). The leading reasons for hospitalization were pneumonia and bronchiolitis. These findings show that RSV diagnosis is useful and it lessens the indiscriminate use of antibiotics.^ieng

Bacteriology of middle ear fluid specimens obtained by tympanocentesis from 111 Colombian children with acute otitis media.

We cultured middle ear fluid specimens obtained by tympanocentesis from 111 Colombian infants and children, ages 11 days to 11 years, with acute otitis media. Bacteria were isolated in 82 patients (74%). Haemophilus influenzae, the most common isolate, was present in 40 cases (36%); 32 were nontypable strains and 8 were type b. Streptococcus pneumoniae, identified in 26 cases (22%), was the second most common pathogen. All H. influenzae and S. pneumoniae strains were susceptible to ampicillin and penicillin, respectively. We conclude that amoxicillin remains the drug of choice for treatment of acute otitis media in our country.

Disseminated histoplasmosis in children: the role of itraconazole therapy.

OBJECTIVES: To describe the clinical characteristics and laboratory diagnosis of seven children with disseminated histoplasmosis and evaluate the effectiveness of itraconazole therapy in this severe form of the mycosis as well as to determine the long term results of such treatment. METHODS: The diagnosis of histoplasmosis was based on the direct observation of Histoplasma capsulatum var. capsulatum and/or on the isolation of the fungus from pathologic materials; the results of the serologic tests were taken into consideration. Chest roentgenograms also contributed to the diagnosis. PATIENTS: The patients were seven rural children, five girls and two boys, ages 1 to 14 years (mean, 4.6), with a confirmed diagnosis of disseminated histoplasmosis and who had no underlying disease other than malnourishment. RESULTS: The seven children experienced a subacute febrile syndrome for 4 months accompanied by anorexia, weight loss and signs of reticuloendothelial involvement such as lymph node hypertrophy, hepatomegaly and/or splenomegaly. The lung revealed roentgenographic alterations consisting mainly of nodular infiltrates. All patients received itraconazole orally in a mean dosage of 7.2 mg/kg/day, for variable periods (3 to 12 months), depending on the individual response and the toxic effects of the medication. One of the patients who was improving after 1 month of treatment was taken from the hospital by his guardian against medical advice and died shortly afterward. The remaining six patients responded to the treatment with marked clinical improvement and showed negative cultures and decreases in anti-H. capsulatum antibody titers after 3 months of treatment. Only one patient, the youngest and most severely affected child, exhibited hepatotoxicity, which subsided when itraconazole was discontinued. Extended follow-up studies revealed no relapses. CONCLUSION: The results of this study indicate that itraconazole is effective for treatment of disseminated childhood histoplasmosis. More studies should be performed to determine the most appropriate dosage and the optimal duration of itraconazole treatment in children.

Distribution of capsular types and antimicrobial susceptibility of invasive isolates of Streptococcus pneumoniae in Colombian children. Pneumococcal Study Group in Colombia.

Streptococcus pneumoniae is the leading bacterial cause of childhood pneumonia in the developing world. This study describes the type distribution and antimicrobial susceptibility of invasive pneumococcal isolates from Colombian children and is part of the Sistema Regional de Vacunas (SIREVA), a PAHO regional initiative designed to determine the ideal serotype composition of a protein polysaccharide pneumococcal conjugate vaccine for use in children less than 5 years old in Latin America. In Colombia, during the study period, centres in Bogota, Medellin, and Cali collected 324 S. pneumoniae isolates from invasive diseases, 238 (73.5%) from children under the age of 2. Pneumonia was the clinical diagnosis in 41.3% cases, meningitis in 41%, and sepsis in 11.2%. The seven most frequent types included 14(21.9%), 5(10.5%), 23F(9.6%), 1(9%), 6B(9%), 19F(7.1%), and 6A(6.2%). The frequency of diminished susceptibility to penicillin (DSP) was 12%, with 8.9% of isolates showing intermediate level resistance and 3.1% showing high level resistance. Among DSP isolates, 23% were also resistant to cefotaxime, 33.3% to erythromycin, 48.7% to chloramphenicol, and 74.3% to trimethoprim/sulfamethoxazole. Multiple resistance was detected in 59% of the isolates that have DSP. Penicillin resistance was associated with types 23F (53.8%) and 14 (25.6%). These data provides information on capsular types prevalent in Colombia that will not only allow the formulation of an ideal vaccine for the region but also reinforce the need for ongoing regional surveillance.

In vitro evaluation of lomefloxacin activity in Colombia.

As part of the worldwide in vitro program to determine the antimicrobial activity of lomefloxacin, our study tested susceptibility of bacterial isolates from hospitals in Medellin, Colombia. A total of 504 bacterial isolates were obtained from patients at three different centers. For Enterobacteriaceae, 0.5 micrograms/ml inhibited 100% of the indole-positive Proteus and Salmonella spp.; 1 microgram/ml inhibited 100% of Shigella and Citrobacter, 2 microgram/ml inhibited 100% of Enterobacter spp., E. coli, Proteus mirabilis, and Serratia marcescens isolates tested. The MIC90 for Klebsiella spp. and Pseudomonas spp. was 4 micrograms/ml. The MIC90 was 4 micrograms/ml for S. aureus and 2 micrograms/ml for S. epidermidis and S. saprophyticus. The MIC90 of Streptococcus spp. were less than or equal to 4 micrograms/ml for all isolates tested. Considering that 97.8% were susceptible to concentrations of less than or equal to 4 micrograms/ml of lomefloxacin, this new quinolone offers potential in the therapy of a variety of systemic infections, especially in patients with multiply resistant pathogens.

Microcolony detection in 7H11 thin layer culture is an alternative for rapid diagnosis of Mycobacterium tuberculosis infection.

SETTING: Radiometric technology and molecular biology are used in rapid diagnosis of tuberculosis in laboratories around the world. However, these technologies increase costs and are not available in laboratories where economic resources are limited. OBJECTIVE: To compare sensitivity and time for detection of positive cultures in a microcolony method, Middlebrook 7H11 thin layer agar plate (TL7H11), and a conventional culture, Lowenstein-Jensen (L-J). DESIGN: A total of 761 clinical samples were processed using acid-fast smear and culture on TL7H11 plates and L-J tubes. TL7H11 plates were checked microscopically for microcolony growth twice weekly for 4 weeks, and L-J tubes were checked once a week for 8 weeks. RESULTS: Overall positivity was 11.0%. More than 60% of the positive samples were detected within the first 10 days on TL7H11, and none on L-J. After 2 weeks, more than 80% were positive on TL7H11 compared to 10% on L-J. In paucibacillary samples, TL7H11 detected 2.18% and L-J 4.57% (P < 0.001). Microcolony morphology was 100% distinctive for Mycobacterium tuberculosis on TL7H11. The calculated cost of TL7H11 prepared in the laboratory was US$2.90 per unit. CONCLUSION: The TL7H11 method is an inexpensive, rapid and reliable alternative for diagnosing M. tuberculosis infection. It is therefore a valuable option for laboratories in low income countries.

Mathematical models of synaptic plasticity: I. Posttetanic potentiation.

A mathematical model of post-tetanic potentiation is proposed. The model uses differential equations and is based upon physiological postulates of the electrical, metabolic, and neuroendocrine activities that are related to synaptic connectivity. These activities may modify some important parameters in synaptic function. In the proposed model these parameters are restricted to the presynapse in view of the physiological evidence indicating that posttetanic potentiation is probably due to presynaptic mechanisms. The model takes into consideration the size of the transmitter pool available for release, the mobilization of transmitter from and to this pool, and the fraction of transmitter released. Based upon the above postulates, we have simulated different phases of the phenomenon of posttetanic potentiation, and we have presented the results of several preparations in which this event has been studied. This work represents a successful attempt to reproduce the dynamics of posttetanic potentiation based upon physiological results with a mathematical model.

Mathematical model of synaptic plasticity: II. Habituation.

A mathematical model of the phenomenon of habituation as a homosynaptic depression of the amount of transmitter release is proposed. The model is based on the physiological studies of habituation in invertebrates and in the spinal cord of vertebrates, where a single synapse has been isolated and some of the physiological mechanisms of this process have been elucidated. The model simulates the following properties of habituation: (1) reduced amount of transmitter release attributed to a repetitive stimulus through changes in the membrane permeability to Ca2+ ions; (2) spontaneous recovery by rest; (3) the amplitude and frequency dependence of habituation; (4) modulation of habituation: sensitization, through an increase in membrane Ca2+ permeability, and presynaptic inhibition, through a reduced depolarization of the physiological stimulus; (5) long-term habituation attributed to repetitive trials of habituation and spontaneous recovery.

Mathematical model of synaptic plasticity: III. Heterosynaptic changes.

A mathematical model, using differential equations, of heterosynaptic plasticity is proposed. The model is based on physiological studies of invertebrates in which nonspecific conditioning, such as sensitization and heterosynaptic inhibition, starts to be elucidated and behavioral studies of classical and instrumental conditioning, which we postulate to have the same mechanisms as those found in nonspecific conditioning. The model permits us to simulate the following heterosynaptic changes: sensitization, heterosynaptic inhibition, classical and instrumental conditioning--including short- and long-term memory--extinction and recuperation--spontaneously and by stimulation.

Clinical and bacteriologic efficacy of amoxycillin b.d. (45 mg/kg/day) versus amoxycillin t.d.s (40 mg/kg/day) in children with group A beta-hemolytic streptococcal tonsillopharyngitis.

This randomized, observer-blind, multicenter, parallel-group study compared the clinical and bacteriologic efficacy and safety of amoxycillin, 45 mg/kg/day b.d. and amoxycillin, 40 mg/kg/day t.d.s. after 7 days of treatment in 517 children with acute bacterial tonsillopharyngitis. At the end of treatment, a successful clinical response was recorded in more than 96% of patients in each of the treatment groups. A similar result was obtained at follow-up. Among those patients who were bacteriologically evaluable at the end of treatment, a successful bacteriologic response was achieved in more than 94% in each treatment group. Both treatments were well tolerated. Drug-related adverse events were recorded in just 12 patients (4.6%) in the b.d. group and six (2.4%) in the t.d.s. group. The study demonstrated that a twice-daily regimen of amoxycillin, 45 mg/kg/day, was as effective and as well tolerated as the standard three-times-daily regimen of amoxycillin, 40 mg/kg/day, in the treatment of acute bacterial tonsillopharyngitis in children.

Cefadroxil monohydrate versus erythromycin in paediatric patients.

Cefadroxil monohydrate, an oral cephalosporin with a long half-life, was compared to erythromycin estolate for efficacy in treating upper respiratory tract infections in children. The study was carried out on forty patients, twenty receiving cefadroxil and twenty receiving erythromycin. Each drug was dosed at 50 mg/kg/day and was given every 12 hours in two equally divided doses. The complete cure rate was 95% for the cefadroxil group and 80% for the erythromycin group. Two patients originally in the erythromycin test group showed no improvement either bacteriologically or clinically after 3 days of treatment. It was found that these patients harboured S. aureus which had become resistant to erythromycin during the course of therapy. Both patients were shifted to cefadroxil treatment and achieved complete cures. Two patients in the erythromycin group and one in the cefadroxil group were diagnosed as having scarlet fever. All three responded clinically, yet cultures from the two treated with erythromycin showed persistence of bacteria while the one treated with cefadroxil proved to be cured both clinically and bacteriologically.

Safety and efficacy of netilmicin in neonates with serious systemic infections.

Twenty-five hospitalized neonates, each with two or more serious symptomatic infections, were given netilmicin by intramuscular injection. The antibiotic was administered usually at 1.5 or 3.0 mg/kg twice a day (q 12 hr) for 7 to 13 days. At the end of therapy the signs and symptoms of infection were completely resolved in twenty-four of the twenty-five patients and markedly improved in the remaining one. Thirty-five causative organisms were isolated from 30 of the 59 infection sites; after netilmicin therapy 31 causative organisms were completely eliminated and 4 were markedly reduced in number. One of the babies had a slight increase in serum creatinine level, possibly related to therapy, and a mild transient rash which was doubtfully related to netilmicin. None of the other neonates had adverse reactions.

Serum levels and urinary concentrations of kanamicin, bekanamicin and amikacin (BB-K8) in diabetic children and a control group.

Serum levels of kanamicin, bekanamicin, and amikacin were studied, after a single intramuscular dose of each antibiotic, in three groups of diabetic children, with their respective normal controls, paired by age, weight and sex. Lower serum levels were observed with kanamicin and bekanamicin in diabetic children compared to their controls. The difference in low serum levels was less noticeable with amikacin.

Amikacin (BBK8) in infections due to gram-negative organisms in children over the age of one month.

Thirty children over the age of one month were treated with amikacin (BBK8), a new aminoglycoside derived from kanamycin A, with three intramuscular dosage schedules. Each group consisted of ten patients. The first received 7-5 mg/kg/12 hours, the second 7-5 mg/kg/24 hours and the third, 3-75 mg/kg/12 hours. The infections and the bacteria were similar in all three groups: pyelonephritis, abscesses of soft tissues, infected wounds, septicaemia, superinfected empyema, gastro-enteritis, chronic otitis media; the bacteria were E. coli, Klebsiella, Pseudomonas and Salmonella. A were sensitive by the Kirby-Bauer method, although two were resistant by dilution in Petri dish. Of the thirty patients, twenty four (80%) were cured. The schedule of 3-75 mg/kg/12 hours was as effective as the schedule of 7-5 mg/kg/12 hours for infections such as pyelonephritis, superficial abscesses, contaminated wounds, gastro-enteritis and sepsis. The cases with infections localized in rather unaccessible sites required double the dose and strict drainage and cleanliness. Plasma levels with the administration of 3-75 mg/kg fluctuated between 8-3 and 12-6 mcg/ml; with 7-5 mg/kg they fluctuated between 8-6 and 13-1. The minimum inhibitory level (MIL) for the majority of the bacteria was 1-25 mcg/ml. No toxic reactions were observed.

Effectiveness of two new cephalosporins, cephazolin and cephapirin, administered intermittently in acute and chronic osteomyelitis in children.

Ten patients were treated, most of pre-school age, with acute osteomyelitis, produced by Staphylococcus aureus and Salmonella, having evolved for approximately one week, with sodium cephazolin at doses of 60 mg/kg/day intramuscularly in two daily injections for the first seven days and then in a single dose every twenty-four hours for four to seven weeks. Nine of ten patients were asymptomatic six months after this treatment. The patient who manifested chronic signs at the end of six weeks of therapy continued to be treated with three weekly injections of the same drug at an equal dose until the completion of six months, at the end of which he was asymptomatic. Ten patients with chronic osteomyelitis having evolved for two months to five years, due to penicillin-resistant Staphylococcus aureus, were treated with cephapirin at the dose of 30 mg/kg in one daily injection intramuscularly for three to four weeks and then the same dose on Mondays, Wednesdays and Fridays until the completion of six months. Eight patients who required it were sequestrectomized. Seven of the ten patients improve and remained asymptomatic for the same period of observation. The three patients who did not show marked clinical improvement did exhibit an appreciable radiological recovery. We have presented these regimens of treatment with a view of encouraging research into the intermittent administration of bactericidal antibiotics for pyogenic infections; in spite of the good results, we do not dare to recommend them in daily practice.

Amikacin in gram-negative paediatric infections.

Amikacin was used in the treatment of various Gram-negative infections in sixty-six children ranging in age from two days to thirteen years. Over 72% of the infections treated were classified as severe and the remainder were moderate. Among infections in which the site of origin was the urinary or gastro-intestinal tract, amikacin achieved thirty-eight (95%) complete or partial cures in forty patients. In respiratory tract infections, amikacin completely or partially cured six (75%) out of eight patients. The remaining eighteen infections involved skin, soft tissue and other miscellaneous categories in which amikacin therapy resulted in seventeen (94%) complete or partial cures. Overall, amikacin achieved fifty-four complete cures and seven clinical or bacteriological cures in sixty-six patients, which represents an 82% complete cure rate and 10% partial cure rate for all the patients in the study.