- Volume 67, Issue 10, 2018
Volume 67, Issue 10, 2018
- Review
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Microbial otitis media: recent advancements in treatment, current challenges and opportunities
More LessOtitis media (OM) is a common disease affecting humans, especially paediatric populations. OM refers to inflammation of the middle ear and can be broadly classified into two types, acute and chronic. Bacterial infection is one of the most common causes of OM. Despite the introduction of vaccines, the incidence of OM remains significantly high worldwide. In this mini-review article, we discuss the recent treatment modalities for OM, such as suspension gel, transcutaneous immunization, and intranasal and transtympanic drug delivery, including therapies that are currently undergoing clinical trials. We provide an overview of how these recent advancements in therapeutic strategies can facilitate the circumvention of current treatment challenges involving preadolescence soft palate dysfunction, biofilm formation, tympanic membrane (ear drum) barrier and the attainment of efficacious drug concentrations in the middle ear. While traditional first-line immunization strategies are generally not very efficacious against biofilms, new technologies that use transdermal or intranasal drug delivery via chitosan–PsaA nanoparticles have shown promising results in experimental animal models of OM. Sustained drug delivery systems such as penta-block copolymer poloxamer 407–polybutylphosphoester (P407-PBP) or poloxamer 407 (e.g. OTO-201, with the brand name ‘OTIPRIO’) have demonstrated that treatments can be reduced to a single topical application. The emergence of effective new treatment modalities opens up promising new avenues for the treatment of OM that could lead to improved quality of life for many children and their families.
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Review of vaccination in pregnancy to prevent pertussis in early infancy
Maternal pertussis vaccination has been introduced in several countries to protect infants from birth until routine infant vaccination takes place. This review assesses existing evidence on the effectiveness and safety of immunization in pregnancy. The search was finalized in April 2017 and was based on searches using several databases. The selection criteria included any experimental or observational study reporting on the immunogenicity, effectiveness or safety of vaccination with a pertussis-containing vaccine in pregnant women and their infants. Following de-duplication and exclusions, we identified 8395 studies, which were reduced to 46 for inclusion. The overall risk of bias was low, with the exception of some early studies and pharmacovigilance safety data. The evidence demonstrates efficient transplacental transfer of maternal antibodies in infants whose mothers were vaccinated with Tdap or Tdap/IPV in pregnancy, with good evidence that this protects against disease in young infants. Safety studies covering more than 150 000 women vaccinated mostly in the late second or third trimesters are generally consistent and provide reassurance of no significant increased risk of recognized maternal conditions or of adverse events (including congenital anomalies) in infants born to vaccinated women. The clinical significance of reduced seroconversion to pertussis following routine immunization is not yet clear, but no increased risk of pertussis in infants whose mothers were vaccinated in pregnancy was found following primary immunizations in North American and English studies. Most post-booster studies suggest that any blunting effect is short-lived and that longer-term protection in infants from active immunization is not compromised.
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- Antimicrobial Resistance
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Excess body weight and age associated with the carriage of fluoroquinolone and third-generation cephalosporin resistance genes in commensal Escherichia coli from a cohort of urban Vietnamese children
Purpose. Antimicrobial-resistant bacterial infections in low- and middle-income countries (LMICs) are a well-established global health issue. We aimed to assess the prevalence of and epidemiological factors associated with the carriage of ciprofloxacin- and ceftriaxone-resistant Escherichia coli and associated resistance genes in a cohort of 498 healthy children residing in urban Vietnam.
Methodology. We cultured rectal swabs onto MacConkey agar supplemented with resistant concentrations of ciprofloxacin and ceftriaxone. Additionally, we screened meta-E. coli populations by conventional PCR to detect plasmid-mediated quinolone resistance (PMQR)- and extended-spectrum β-lactamase (ESBL)-encoding genes. We measured the associations between phenotypic/genotypic resistance and demographic characteristics using logistic regression.
Results/Key findings. Ciprofloxacin- and ceftriaxone-resistant E. coli were cultured from the faecal samples of 67.7 % (337/498) and 80.3 % (400/498) of children, respectively. The prevalence of any associated resistance marker in the individual samples was 86.7 % (432/498) for PMQR genes and 90.6 % (451/498) for β-lactamase genes. Overweight children were significantly more likely to carry qnr genes than children with lower weight-for-height z-scores [odds ratios (OR): 1.24; 95 % confidence interval (CI): 10.5–1.48 for each unit increase in weight for height; P=0.01]. Additionally, younger children were significantly more likely to carry ESBL CTX-M genes than older children (OR: 0.97, 95 % CI: 0.94–0.99 for each additional year, P=0.01).
Conclusion. The carriage of genotypic and phenotypic antimicrobial resistance is highly prevalent among E. coli in healthy children in the community in Vietnam. Future investigations on the carriage of antimicrobial resistant organisms in LMICs should focus on the progression of carriage from birth and structure of the microbiome in obesity.
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Resistance pattern and distribution of carbapenemase and antiseptic resistance genes among multidrug-resistant Acinetobacter baumannii isolated from intensive care unit patients
More LessPurpose. Nosocomial infections caused by multidrug resistant Acinetobacter baumannii have emerged as a serious problem in healthcare settings worldwide.
Methodology. A total of 100 A. baumannii clinical isolates from immunocompromised patients hospitalized in ICUs in Iran were investigated for antimicrobial susceptibility and the presence of carbapenemase and antiseptic resistance genes.
Results. All isolates were resistant to one or more antibiotics, with the most frequent resistance found against ciprofloxacin and imipenem (100 %) and piperacillin (99 %). The MICs of biocides were determined by the agar dilution method. No apparent resistance to biocides was seen among the 100 A. baumannii isolates. All isolates were effectively inhibited by the user’s defined concentrations of cetrimide, benzalkonium chloride and glutardaldehyde. The intrinsic β-lactamase gene, bla OXA-51-like, was detected in all A. baumannii isolates. Coexistence of bla OXA-51 andbla OXA-23 was encountered in 89 % of isolates. However, genes bla OXA-58, bla SIM and bla IMP were not detected in any isolates. While A. baumannii isolates were sensitive to biocides, they carried qac genes with the qacEΔ1 gene being the most common, at a frequency of 91 %.
Conclusion. Our study revealed the high frequency of multidrug- and carbapenem-resistant isolates of A. baumannii in ICU patients, with a high prevalence of the genes bla OXA-23 and bla OXA-51. However, no apparent biocide resistance was seen in A. baumannii isolates. It appears that appropriate surveillance and control measures are essential to prevent the emergence and transmission of MDR A. baumannii in Iran.
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Evaluation of rapid KPC carbapenemase detection method based on MALDI-TOF VITEK MS spectra analysis
Clinical microbiology laboratories in hospital settings need to be able to identify patients who carry carbapenemase-producing bacterial strains quickly in order to contain their spread and initiate proper pharmacological therapy. The aim of this study was to confirm the correlation between KPC production and a characteristic mass spectrometry (MS) peak (11 109 Da±8) to validate the use of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS as a rapid screening tool. With this aim, 176 selected clinical samples that were KPC-producing and 260 control samples that were carbapenem-susceptible or carbapenem-resistant through other resistance mechanisms, or were producing hydrolytic enzymes other than KPC, were analysed. The presence of the 11 109 Da peak in the spectra of 99.4 % (175/176) of the KPC-producing strains compared to the controls, which all lacked the peak, confirmed a strong correlation between KPC production and the presence of the 11 109 Da peak in the MALDI-TOF MS spectrum. The high sensitivity (98.7 %) and specificity (100 %) of the peak searching in the MALDI-TOF MS spectra mean that 11 109 Da peak searching is a suitable screening tool in KPC-endemic regions.
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- Clinical Microbiology
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Icelandic ovine Mycoplasma ovipneumoniae are variable bacteria that induce limited immune responses in vitro and in vivo
More LessPurpose. Mycoplasma ovipneumoniae is a pathogen that causes atypical pneumoniae in sheep and goats. While infection of lambs can induce strong immune responses, typically measured as serum antibodies, experimental vaccines appear to induce lower antibody titres. The purpose of this study was to better understand the bacterium and its interaction with the host, in order to improve the vaccination strategy.
Methodology. We designed primers to compare seven M. ovipneumoniae gene sequences, in addition to the 16S sequence typically used, to estimate the variability between isolates. In addition, we labelled bacteria with a two-step process to examine whether bacteria could be intracellular as well as on the host surface in vitro. Finally, we vaccinated sheep four times and examined the induction of humoral and cellular responses.
Results. We were able to reliably amplify the seven housekeeping gene sequences to examine variability of the different isolates, and the bacteria could be found intracellularly, as well as on the host cell surface. Four vaccinations of sheep produced only modest humoral and cellular responses in this study, likely due to previous exposure of the animals to mycoplasmas.
Conclusions. The moderate immune responses seen in this study indicate that previous exposure to mycoplasmas is a challenge for vaccination of lambs against M. ovipneumoniae. However, an alternative vaccination strategy, e.g. utilizing a recombinant vaccine, may overcome this vaccination hurdle in endemic regions and we suggest a possible vaccine candidate.
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Aerosolization of Mycobacterium avium and Mycobacterium abscessus from a household ultrasonic humidifier
More LessPurpose. To measure the aerosolization of Mycobacterium avium subspecies hominissuis and Mycobacterium abscessus subspecies abscessus from ultrasonic humidifiers.
Methodology. An ultrasonic humidifier was filled with sterile tap water and inoculated with water-acclimated cells of either the M. avium or M. abscessus strains to achieve a range of densities similar to those of mycobacteria found in drinking waters. During operation of the humidifier, aerosols were collected using an Andersen 6-Stage Cascade Sampler.
Results. Cells of the M. avium and M. abscessus strains were readily aerosolized and recovered in particles (1–5 µm diameter); small enough to enter the furthest reaches of the human lung. Aerosolization of M. abscessus was significantly reduced in the presence of a normal drinking water bacterial flora. Significantly greater numbers of M. avium cells were aerosolized from high-density suspensions (1200 c.f.u. ml−1), than from low-density (120 c.f.u. ml−1) and very low-density (12 c.f.u. ml−1) suspensions.
Conclusions. This report documents the potential for M. avium subspecies hominissuis and M. abscessus subspecies abscessus cells in drinking water to be aerosolized from one type of portable humidifier; an ultrasonic humidifier. Care should be taken in using an ultrasonic humidifier where an individual at risk for mycobacterial pulmonary disease could be exposed.
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Role of BK polyomavirus (BKV) and Torque teno virus (TTV) in liver transplant recipients with renal impairment
Purpose. Renal impairment is a common complication after liver transplantation (LT). While BK polyomavirus (BKV) has been linked to renal failure in kidney transplant recipients, Torque teno virus (TTV) is a surrogate marker for immunosuppression that does not have a clear association with any human disease. The impact of BKV and TTV on renal impairment after LT is unknown.
Methodology. In this retrospective study, urine and serum samples from 136 liver transplant recipients were screened for BKV and TTV by quantitative PCR. In addition, serum was screened for BKV-specific antibodies and the VP1 typing region was sequenced for BKV genotyping. All parameters were correlated with clinical data.
Results/Key findings. BK viruria was detected up to 21 years after transplantation in 16.9 % of cases. BK viraemia was detected in 8.7 % of patients with BK viruria up to 4 years after LT. BKV-specific antibodies were detected in 93.6 % of all LT recipients and correlated with BKV viral load in urine. There was no correlation between renal impairment and the detection of BK DNA in urine (OR 0.983). TTV DNA was detected in 84.6 % of serum samples and in 66.6 % of urine samples. The TTV viral load in serum correlated with the BKV viral load but had no impact on renal impairment.
Conclusion. Our data indicate that the detection of BKV and TTV is not a risk factor for renal impairment after LT. A correlation of TTV and BKV viral load seems to be an indicator for the immune status of the host.
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Development and validation of a multiplex reverse transcript real-time PCR for E6/E7 mRNA detection of high-risk human papillomavirus
More LessPurpose. Human papillomavirus (HPV) E6/E7 mRNA is a more specific marker for cervical lesion screening than HPV DNA. Here, we aimed to develop a new one-step multiplex reverse transcript real-time PCR (MRT-PCR) to detect E6/E7 mRNA from 14 high-risk HPV (hrHPV) genotypes.
Methodology. The analytical sensitivity and specificity of the MRT-PCR system were validated. Its clinical performance was evaluated by comparing the results with bDNA signal amplification assay and histopathological results.
Results. The detection limit of MRT-PCR was 20 to 200 copies per reaction of different HPV genotypes, and no cross-reactivity was observed with any other low-risk HPV or other pathogens commonly found in the female genital tract. Using the bDNA signal amplification assay for comparison, a test on 166 clinical samples showed that the overall agreement between the two methods was 95.18 % and the one-step MRT-PCR was more sensitive. Further, compared with the histopathological results for the 166 clinical samples, the sensitivity and specificity of the MRT-PCR method were 88.9 and 71.6 %, respectively, and the positive rate for hrHPV E6/E7 mRNA increased with the severity of the cervical lesions.
Conclusion. The one-step multiplex RT-PCR for E6/E7 mRNA detection is a simple, fast, universally applicable, sensitive and highly specific method for hrHPV E6/E7 mRNA detection. It is reliable for cervical lesion screening and of potential value in future clinical applications.
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- Disease, Diagnosis and Diagnostics
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Correlation between serum cryptococcal antigen titre and meningitis in immunocompetent patients
The aim of this paper was to determine the correlation between serum cryptococcal antigen and a diagnosis of cryptococcal meningitis in the immunocompetent cohort. A retrospective multicentre analysis of immunocompetent patients diagnosed and treated for cryptococcal meningitis between January 2000 and December 2017 was performed. Sixty-seven of the 143 cases of cryptococcosis occurred in immunocompetent patients. The serum cryptococcal antigen titre was significantly higher in the meningitis group [1 : 256 (IQR: 64–1024)] compared with that for non-meningitis patients [1 : 64 (IQR: 8–256)], P=0.012. The relative risk of meningitis with a serum cryptococcal antigen (CRAG) >1 : 64 was 1.8 (95 % CI: 1.15–2.82). This study demonstrates a clear correlation between serum cryptococcal antigen titre and meningitis. While the serum titre is not definitive for meningitis, in resource-limited settings or cases where lumbar puncture may be contraindicated, this evidence may aid diagnosis and subsequent therapeutic decisions.
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- Microbial Ecology and Health
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Characterization of pelvic and cervical microbiotas from patients with pelvic inflammatory disease
More LessPurpose. The aims of this work were: (i) to profile and compare pelvic and cervical microbiota from patients with pelvic inflammatory disease (PID); (ii) to test the ascending infection hypothesis that the microbes in the vagina or cervix spread to the upper genital tract and cause PID.
Methodology. Thirty-eight PID patients and 19 control patients were enrolled in this study and received salpingectomy or salpingo-oophorectomy. Both pelvic and cervical samples were collected during surgery, which were subject to culture diagnosis and next-generation sequencing (NGS)-based 16S rRNA profiling.
Results. For the PID group, the NGS-based method revealed that half of the pelvic samples were dominated by a single organism while the other half exhibited a polymicrobial infection. The pelvic and cervical microbiota were similar in terms of both taxonomic richness and evenness. Pelvic microbiota was dominated by Acinetobacter, Escherichia, Sneathia and Streptococcus whereas cervical microbiota was dominated by Lactobacillus and Gardnerella. Only six pelvic samples were positive by culture diagnosis, three of which matched the NGS-based results. The PID group was further divided into 23 hydrosalpinx and 15 pyosalpinx samples according to the pelvic mass collected during surgery, the former showing a richer bacterial composition than the latter.
Conclusion. The NGS-based method provides a more informative profile of pelvic microbiota than the culture method. The pelvic and cervical microbiota from the same patient were inconsistent with each other, and thus therapeutic decisions based on cervical microbiota may lead to antimicrobial misuse.
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- Pathogenicity and Virulence/Host Response
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Intranasal coinfection model allows for assessment of protein vaccines against nontypeable Haemophilus influenzae in mice
Purpose. Nontypeable Haemophilus influenzae (NTHi) is a commensal in the human nasopharynx and the cause of pneumonia, meningitis, sinusitis, acute exacerbations of chronic obstructive pulmonary disease and acute otitis media (AOM). AOM is the most common ailment for which antibiotics are prescribed in the United States. With the emergence of new strains of antibiotic-resistant bacteria, finding an effective and broad coverage vaccine to protect against AOM-causing pathogens has become a priority. Mouse models are a cost-effective and efficient way to help determine vaccine efficacy. Here, we describe an NTHi AOM model in C57BL/6J mice, which also utilizes a mouse-adapted H1N1 influenza virus to mimic human coinfection.
Methodology. We tested our coinfection model using a protein vaccine formulation containing protein D, a well-studied NTHi vaccine candidate that can be found in the 10-valent Streptococcus pneumoniae conjugate vaccine. We verified the usefulness of our mouse model by comparing bacterial loads in the nose and ear between protein D-vaccinated and control mice.
Results. While there was no measurable difference in nasal bacterial loads, we did detect significant differences in the bacterial loads of ear washes and ear bullae between vaccinated and control mice.
Conclusion. The results from this study suggest that our NTHi AOM coinfection model is useful for assessing protein vaccines.
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- Corrigendum
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Volumes and issues
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Volume 73 (2024)
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Volume 72 (2023 - 2024)
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Volume 71 (2022)
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Volume 70 (2021)
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Volume 69 (2020)
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Volume 68 (2019)
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Volume 67 (2018)
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Volume 66 (2017)
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Volume 65 (2016)
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Volume 64 (2015)
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Volume 63 (2014)
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Volume 62 (2013)
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Volume 61 (2012)
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Volume 60 (2011)
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Volume 59 (2010)
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