In vitro susceptibility of ceftaroline against clinically important Gram-positive cocci, Haemophilus species and Klebsiella pneumoniae in Taiwan: Results from the Antimicrobial Testing Leadership and Surveillance (ATLAS) in 2012-2018.

BACKGROUND/PURPOSE: Ceftaroline, with a unique activity against methicillin-resistant Staphylococcus aureus (MRSA), was not launched in Taiwan before 2019. The in vitro susceptibility data of ceftaroline against important Taiwanese pathogens are lacking. METHODS: The in vitro susceptibility of ceftaroline against important pathogens collected from 2012 through 2018 were extracted from the Antimicrobial Testing Leadership and Surveillance program. Broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) to ceftaroline against all isolates. RESULTS: During the study period, the in vitro data regarding isolates of S. aureus (n = 2049), Staphylococcus epidermidis (n = 185), Streptococcus pneumoniae (n = 334), Streptococcus pyogenes (n = 170), Haemophilus influenzae (n = 75), Haemophilus parainfluenzae (n = 10) and Klebsiella pneumoniae (n = 680) regardless of hospital sites of collection were analyzed. Among the S. aureus isolates studied, 19.4% showed MICs of 1 mg/L to ceftaroline, and 4.4% showed in vitro susceptible-dose dependent to ceftaroline (all MICs, 2 mg/L). Most of other Gram-positive cocci, all H. influenzae and H. parainfluenzae isolates were susceptible to ceftaroline. By contrast, about one-third (35.9%) of K. pneumoniae isolates, irrespective of infection sources, exhibited non-susceptibility to ceftaroline (MIC range, 0.015-256 mg/L; MIC50 and MIC90 values, 0.12 and 256 mg/L, respectively). CONCLUSIONS: From the pharmacodynamic perspectives, the ceftaroline dosage of 600 mg as a 2-h intravenous infusion every 8 h is effective against all S. aureus and other Gram-positive isolates regardless of acquisition sites in Taiwan. Before ceftaroline is prescribed in treatment of the patient with Gram-negative infection, a cautious evaluation about patient's healthcare-associated factor is warranted.

Comparative analysis of the pulmonary microbiome in healthy and diseased pigs.

The lungs possess an effective antimicrobial system and a strong ability to eliminate microorganisms in healthy organisms, and were once considered sterile. With the development of culture-independent sequencing technology, the richness and diversity of porcine lung microbiota have been gaining attention. In order to study the relationship between lung microbiota and porcine respiratory disease complex (PRDC), the lung microbiota in healthy and diseased swine bronchoalveolar lavage fluids were analyzed and compared using the Illumina MiSeq sequencing platform. The predominant microbial communities of healthy and diseased swine were similar at the phylum level, mainly composed of Proteobacteria, Firmicutes, Tenericutes, and Bacteroidetes. However, the bacterial taxonomic communities of healthy and diseased swine differed at the genus level. The higher relative abundances of Lactococcus, Enterococcus, Staphylococcus, and Lactobacillus genera in healthy swine might provide more benefits for lung health, while the enhanced richness of Streptococcus, Haemophilus, Pasteurella, and Bordetella genera in diseased swine might be closely related to pathogen invasion and the occurrence of respiratory disease. In conclusion, the observed differences in the richness and diversity of lung microbiota can provide novel insights into their relationship with PRDC. Analyses of swine lung microbiota communities might produce an effective strategy for the control and prevention of respiratory tract infections.

The microbiome in bronchiectasis.

Bronchiectasis is increasing in prevalence worldwide, yet current treatments available are limited to those alleviating symptoms and reducing exacerbations. The pathogenesis of the disease and the inflammatory, infective and molecular drivers of disease progression are not fully understood, making the development of novel treatments challenging. Understanding the role bacteria play in disease progression has been enhanced by the use of next-generation sequencing techniques such as 16S rRNA sequencing. The microbiome has not been extensively studied in bronchiectasis, but existing data show lung bacterial communities dominated by Pseudomonas, Haemophilus and Streptococcus, while exhibiting intraindividual stability and large interindividual variability. Pseudomonas- and Haemophilus-dominated microbiomes have been shown to be linked to severe disease and frequent exacerbations. Studies completed to date are limited in size and do not fully represent all clinically observed disease subtypes. Further research is required to understand the microbiomes role in bronchiectasis disease progression. This review discusses recent developments and future perspectives on the lung microbiome in bronchiectasis.

Enterotype-based Analysis of Gut Microbiota along the Conventional Adenoma-Carcinoma Colorectal Cancer Pathway.

The dysbiosis of human gut microbiota is strongly associated with the development of colorectal cancer (CRC). The dysbiotic features of the transition from advanced polyp to early-stage CRC are largely unknown. We performed a 16S rRNA gene sequencing and enterotype-based gut microbiota analysis study. In addition to Bacteroides- and Prevotella-dominated enterotypes, we identified an Escherichia-dominated enterotype. We found that the dysbiotic features of CRC were dissimilar in overall samples and especially Escherichia-dominated enterotype. Besides a higher abundance of Fusobacterium, Enterococcus, and Aeromonas in all CRC faecal microbiota, we found that the most notable characteristic of CRC faecal microbiota was a decreased abundance of potential beneficial butyrate-producing bacteria. Notably, Oscillospira was depleted in the transition from advanced adenoma to stage 0 CRC, whereas Haemophilus was depleted in the transition from stage 0 to early-stage CRC. We further identified 7 different CAGs by analysing bacterial clusters. The abundance of microbiota in cluster 3 significantly increased in the CRC group, whereas that of cluster 5 decreased. The abundance of both cluster 5 and cluster 7 decreased in the Escherichia-dominated enterotype of the CRC group. We present the first enterotype-based faecal microbiota analysis. The gut microbiota of colorectal neoplasms can be influenced by its enterotype.

Preliminary analysis of salivary microbiome and their potential roles in oral lichen planus.

Several studies have explored the origin and development mechanism of oral lichen planus (OLP) with limited attention to the role of bacteria in the progression of this common oral disease. Here we utilized MiSeq sequencing of 16S rRNA gene amplicons to identify complex oral microbiota associated with OLP from saliva samples of two subtypes (reticular and erosive) of OLP patients and healthy controls. Our analyses indicated that the overall structure of the salivary microbiome was not significantly affected by disease status. However, we did observe evident variations in abundance for several taxonomic groups in OLP. Porphyromonas and Solobacterium showed significantly higher relative abundances, whereas Haemophilus, Corynebacterium, Cellulosimicrobium and Campylobacter showed lower abundances in OLP patients, as compared with healthy controls. In addition, we explored specific microbial co-occurrence patterns in OLP, and revealed significantly fewer linkers of Streptococcus comprising species in erosive OLP. Furthermore, the disease severity and immune dysregulation were also genus-associated, including with Porphyromonas that correlated to disease scores and salivary levels of interleukin (IL)-17 and IL-23. Overall, this study provides a general description of oral microbiome in OLP, and it will be useful for further investigation of their potential roles in the initiation and immune modulation of OLP.

No development of ciprofloxacin resistance in the Haemophilus species associated with pneumonia over a 10-year study.

BACKGROUND: The widespread overuse of antibiotics promotes the development of antibiotic resistance in bacteria, which can cause severe illness and constitutes a major public health concern. Haemophilus species are a common cause of community- and nosocomial-acquired pneumonia. The antibiotic resistance of these Gram-negative bacteria can be prevented through the reduction of unnecessary antibiotic prescriptions, the correct use of antibiotics, and good hygiene and infection control. This article examines, retrospectively, antibiotic resistance in patients with community- and nosocomial-acquired pneumonia caused by Haemophilus species. METHODS: The demographic, clinical, and laboratory data of all patients with community- and nosocomial-acquired pneumonia caused by Haemophilus species were collected from the hospital charts at the HELIOS Clinic, Witten/Herdecke University, Wuppertal, Germany, within a study period from 2004 to 2014. Antimicrobial susceptibility testing was performed for the different antibiotics that have been consistently used in the treatment of patients with pneumonia caused by Haemophilus species. RESULTS: During the study period of January 1, 2004, to August 12, 2014, 82 patients were identified with community- and nosocomial-acquired pneumonia affected by Haemophilus species. These patients had a mean age of 63.8 ± 15.5 (60 [73.2%, 95% CI 63.6%-82.8%] males and 22 [26.8%, 95% CI 17.2%-36.4%] females). Haemophilus species had a high resistance rate to erythromycin (38.3%), ampicillin (24.4%), piperacillin (20.8%), cefuroxime (8.5%), ampicillin-sulbactam (7.3%), piperacillin-sulbactam (4.3%), piperacillin-tazobactam (2.5%), cefotaxime (2.5%), and levofloxacin (1.6%). In contrast, they were not resistant to ciprofloxacin in patients with pneumonia (P = 0.016). CONCLUSION: Haemophilus species were resistant to many of the typically used antibiotics. Resistance toward ciprofloxacin was not detected in patients with pneumonia caused by Haemophilus species.

Haemophilus haemolyticus is infrequently misidentified as Haemophilus influenzae in diagnostic specimens in Australia.

The commensal Haemophilus haemolyticus is difficult to differentiate from the respiratory pathogen Haemophilus influenzae using phenotypic tests. In a study that used molecular tests to retrospectively identify 447 phenotypically identified H. influenzae isolates from diagnostic specimens in Australia, only 7 (1.5%) H. haemolyticus were identified.

Poor clinical outcome for meningitis caused by Haemophilus influenzae serotype A strains containing the IS1016-bexA deletion.

Since the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines, meningitis caused by serotypes other than Hib has gained in importance. We conducted active hospital-based surveillance for meningitis over an 11-year period in Salvador, Brazil. H. influenzae isolates were serotyped and analyzed by polymerase chain reaction, pulsed-field gel electrophoresis, and DNA sequencing to identify strains with a specific deletion (IS1016) in the bexA gene (IS1016-bexA). We identified 43 meningitis cases caused by non-type b H. influenzae: 28 (65%) were caused by type a (Hia), 9 (21%) were caused by noncapsulated strains, and 3 (7%) each were caused by types e and f. Hia isolates clustered in 2 clonal groups; clonal group A strains (n = 9) had the IS1016-bexA deletion. Among children <5 years of age, meningitis caused by Hia from clonal group A had higher case-fatality than meningitis caused by clonal group B. Despite small numbers, these results indicate that the presence of the IS1016-bexA deletion is associated with enhanced virulence in non-type b H. influenzae.

Epidural abscess caused by Haemophilus aphrophilus misidentified as Pasteurella species.

Haemophilus aphrophilus is one of the normal oropharyngeal flora and rarely implicated as a pathogen of spinal infection. A case of H. aphrophilus bacteremia complicated with epidural abscess, psoas muscle abscess, and spondylodiscitis is described in this report. The pathogen was mis-identified as Pasteurella spp. at the very start, and was confirmed by the molecular method. He was successfully treated with adequate antibiotics and surgery. The clinical features of sixteen previously reported cases of spinal infection caused by H. aphrophilus are reviewed.

Anemia falciforme / Sickle cell anemia

La anemia falciforme o drepanocitosis es una hemoglobinopatía estructural congénita que ha aumentado su prevalencia en España en la última década. Se caracteriza por una morfología del hematíe como una hoz, producida por la formación de polímeros de hemoglobina S en la célula. Esto ocasiona anemia hemolítica y trombosis. La clínica más frecuente es la siguiente: crisis de dolor óseo por vaso oclusión, accidentes cerebrovasculares, infiltrados pulmonares, secuestro esplénico, asplenia funcional y disfunción de varios órganos. El tratamiento se basa en la educación sanitaria para el reconocimiento de los síntomas de alarma, la vacunación frente a gérmenes encapsulados, la profilaxis con penicilina, las transfusiones en situaciones seleccionadas, los estimuladores de la producción de hemoglobina fetal y, en casos graves, el trasplante de progenitores hematopoyéticos de hermano compatible(AU)

Sickle cell anemia, or drepanocytosis, is a congenital structural hemoglobinopathy that has become increasingly prevalent in Spain over the past decade. It is characterized by sickles hapedred blood cells produced as a result of the formation of hemoglobin S polymers in the cell. This leads to the development of hemolytic anemia and thrombosis. The most common clinical signs are episodes of bone pain associated with vessel occlusion, stroke, pulmonary infiltrates, splenic sequestration, functional asplenia and multiple organ dysfunction. Treatment is based on health education focusing on the recognition of the warning signs, vaccination against encapsulated bacteria, penicillin prophylaxis, transfusions in selected situations, stimulators of fetal hemoglobin and, in severe cases, transplantation of hematopoietic progenitors from a compatible sibling(AU)

Infecções respiratórias altas: dor de garganta / Upper respiratory infections

As doenças das vias aéreas superiores fazem parte da rotina diária dos ambulatórios de Clínica Médica. O presente artigo destaca as doenças da orofaringe, em especial o sintoma de dor de garganta. Enfatiza os principais agentes etiológicos, por exemplo, vírus, bactérias ou fungos. Descreve o diagnóstico clínico, os exames complementares e a terapêutica específica para cada caso.

Ventriculitis por Haemophilus aphrophilus en un paciente de 21 años con shunt derecha-izquierda / Ventriculites due to Haemophilus aphrophilus in a 21 year old patient and right-left shunt

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Eustachian tube gland tissue changes are related to bacterial species in acute otitis media.

BACKGROUND AND OBJECTIVE: Prior investigations have shown that the number of mucus producing goblet cells in the middle ear and Eustachian tube (ET) mucosa is highly increased during and up to at least six months after experimental acute otitis media (AOM) caused by Streptococcus pneumoniae (SP). Further, the volume of the mucus producing paratubal gland components is increased up to 3 months after the acute infection. These changes may in conjunction with a deteriorated ET function predispose a subsequent development of secretory otitis media. The present investigation compares changes in goblet cell density and gland structures of the ET during and after AOM caused by various bacteria typically encountered in this disease, with emphasis on potential differences due to bacterial species. METHODS: Rat models of AOM caused by SP, non-typeable or type b Haemophilus influenzae (NTHI/HIB) or Moraxella catarrhalis (MC) were studied longitudinally up to 6 months after bacterial challenge. The ET was dissected and decalcified, paraffin embedded and serially sectioned, followed by PAS/alcian blue staining. The goblet cell density and the paratubal gland composition and volume were determined morphometrically in every 20th section, using a light microscope. RESULTS: Regardless of bacterial species, the ET goblet cell density was increased from day 8 and peaked day 16, followed by some degree of normalisation, although not reaching normal numbers within the 6 month period, except for MC. The highest increase was seen in AOM caused by the non-typeable Haemophilus strain, followed by HIB, SP and MC. Except with MC, pathological intra-epithelial glands formed and goblet cells were found in mucosal areas normally devoid of these. In all species but MC, the volume of the paratubal glands progressed to peak 16 days post-inoculation, followed by a gradual normalisation. The volume was still increased 3 months after the acute infection, but completely normalised after 6 months. The increase was primarily due to hypertrophy of the mucous gland components and highest in AOM caused by the Haemophilus species, followed by SP. CONCLUSION: The Eustachian tube goblet cell density is increased during and up to at least six months after AOM regardless of bacterial species, except when employing MC, by which the density was increased for a few weeks only. Except in AOM caused by MC, the volume of the ET glands increases during and up to at least 3 months after infection, primarily due to hypertrophy of the mucous gland components. The non-typeable Haemophilus strain induced the highest increase of both goblet cell density and mucous gland volume. The increased secretory capacity of the ET following AOM may by excessive mucus secretion contribute to the deteriorated ET function found after AOM and thus predispose, sustain or aggravate middle ear disease.

Levels of nicotinamide adenine dinucleotide in extracellular body fluids of pigs may be growth-limiting for Actinobacillus pleuropneumoniae and Haemophilus parasuis.

During infection, nutrient deprivation can alter bacterial phenotype. This, in turn, may have implications for pathogenesis and prophylaxis. Actinobacillus pleuropneumoniae (biotype 1) and Haemophilus parasuis, respiratory tract pathogens of swine, are both V-factor-dependent. The concentrations of V factor in the extracellular fluids of pigs are unknown and may limit the growth of these bacteria in vivo. The aim of this study was to determine the concentrations of nicotinamide adenine dinucleotide (NAD) in select porcine body fluids and to compare the availability of NAD in vivo with the affinities of the organisms for this compound. Levels in plasma, tissue fluids (peritoneal, pleural, synovial, and cerebrospinal), and laryngeal, tracheal, and lung washings were determined with an enzymatic cycling assay. We concluded that, although the NAD supply in the respiratory tract is probably not growth-limiting, it may become limiting if the organisms are disseminated.

Naturally-farrowed, artificially-reared pigs as an alternative model for experimental infection by Haemophilus parasuis.

The use of naturally-farrowed, artificially-reared piglets as an alternative model to study Haemophilus parasuis infections was evaluated. Two trials were performed in order to evaluate the proposed model. In trial 1, animals were vaccinated and challenged with H. parasuis. Results showed that the proposed model was effectively used to evaluate protective immunity against this organism. In trial 2, animals were challenged with different doses of H. parasuis. Results showed that the severity of clinical signs and lesions tended to increase with higher doses. The reproduction of clinical signs and lesions characteristic of H. parasuis systemic infection was successful in both trials, proving that this model is a viable alternative to specific-pathogen free and cesarean-derived, colostrum-deprived pigs.

An appraisal of the potential for illegitimate recombination in bacterial genomes and its consequences: from duplications to genome reduction.

An exhaustive search for shortly spaced repeats in 74 bacterial chromosomes reveals that they are much more numerous than is usually acknowledged. These repeats were divided into five classes: close repeats (CRs), tandem repeats (TRs), simple sequence repeats (SSRs), spaced interspersed direct repeats, and "others." CRs are widespread and constitute the most abundant class, particularly in coding sequences. The other classes are less frequent, but each individual element shows a higher potential for recombination, when the number of repeats and their distances are taken into account. SSRs and TRs are more frequent in pathogens, as expected given their role in contingency loci, but are also widespread in the other bacteria. The analysis of CRs shows that they have an important role in the evolution of genomes, namely by generating duplications and deletions. Several cases compatible with a significant role of small CRs in the formation of large repeats were detected. Also, gene deletion in Buchnera correlates with repeat density, suggesting that CRs may lead to sequence deletion in general and genome reductive evolution of obligatory intracellular bacteria in particular. The assembly of these results indicates that shortly spaced repeats are key players in the dynamics of genome evolution.

Infections with Haemophilus species in chronic granulomatous disease: insights into the interaction of bacterial catalase and H2O2 production.

Chronic granulomatous disease (CGD) is a rare inherited disorder in which phagocytes are incapable of generating bactericidal-reactive oxygen derivatives. Typically these patients are susceptible to life-threatening infections with catalase-producing organisms. Haemophilus species, particularly H. paraphrophilus, are not associated with CGD infections, because these organisms rarely if ever produce catalase. Haemophilus species are part of the indigenous oral microbial flora and, other than H. influenzae, are rarely recognized as pathogens. They are fastidious and require additional growth factors and capnophilic culture conditions for optimal growth and identification. Here we describe three cases of infection with non-H. influenzae (NHI) Haemophilus species in CGD patients. These organisms were catalase-negative and therefore not expected to be virulent in CGD patients, but they were also H(2)O(2) production-negative, thereby negating the putative loss of virulence of being catalase-negative. These are the first reports of NHI Haemophilus species in CGD and reinforce the critical need for careful microbiologic evaluation of infections in CGD patients.

Haemophilus parainfluenzae infection of respiratory mucosa.

The pathogenicity of Haemophilus parainfluenzae (Hpi) in the respiratory tract is unclear, in contrast to the accepted pathogenicity of its close relative non-typable H. influenzae. We have investigated the interaction of two Hpi isolates with the mucosa of adenoid and bronchial tissue organ cultures. The adherence of bacteria to the mucosa of organ cultures, the effect of broth culture filtrates on human nasal epithelium, and interleukin (IL)-8 production by A549 cell cultures was investigated. Hpi 4846 adhered infrequently in clusters of pleomorphic cocco-bacilli to areas of epithelial damage, mucus and unciliated cells in adenoid organ culture experiments at 24 h, but not bronchial mucosa. Hpi 3698 was seen in only one adenoid and no bronchial organ cultures at 24 h. In separate experiments, Hpi 3698 was cleared more rapidly from the centre of the adenoid organ culture and was not cultured at 24 h. Although not adhering to the mucosa at 24 h, Hpi 3698, but not Hpi 4846, caused an increase in the amount of epithelial damage in both types of organ culture. Broth culture filtrates of both strains caused immediate slowing of ciliary beat frequency that progressed, and disrupted epithelial integrity. Dialysed culture filtrates of both strains stimulated IL-8 production by A549 cells, with the culture filtrate of Hpi 3698 being most potent. We conclude that two strains of Hpi varied in their adherence to adenoid tissue, and neither adhered to bronchial tissue. These results lead us to speculate that Hpi is only likely to be a pathogen in the lower respiratory tract when impaired airway defences delay bacterial clearance.