A systematic review and meta-analysis on the antibiotic resistance of Neisseria meningitidis in the last 20 years in the world

BackgroundNeisseria meningitidis is one of the most important causes of meningitis and pathogens-associated deaths in developing and developed countries. Effective anti-microbial agents are pivotal to treat and control N. meningitidis infections. The aim of the present study was to systematically review published studies on the antibiotic resistance of N. meningitidis in the last 20 years (2000–2020) in the world.MethodsPublished researches were identified through a literature search using reputable databases including PubMed, Scopus, and Web of Science. Finally, 24 studies were included for a random-effects model meta-analysis.ResultsThe overall resistance to most commonly used antibiotics such as ceftriaxone, cefotaxime, ciprofloxacin and rifampin was low, ranging from 1 to 3.4%. However, non-sensitivity to penicillin, as the first-line antibiotic against N. meningitidis, was higher (27.2%). Altogether, the resistance to the first-line antibiotics (except penicillin) is still low indicating these drugs are effective against meningococcal meningitis. We also found a significant gap between MIC and disk diffusion for evaluating resistance to antibiotics in which disk diffusion overestimate the resistance rate.ConclusionsTo properly management and prevent the spread of N. miningitidis isolates resistant antibiotics, it is necessary to monitor the pattern of antibiotic susceptibility regionally and globally using the MIC methods.     

Methemoglobinemia

Oxygen transport, the major function of hemoglobin, is dependent upon reduced heme iron. In the red cell, the heme iron is maintained in the reduced form by the methemoglobin reduction system. When the balance between oxidation and reduction of heme iron is perturbed due to the presence of excessive oxidants, decreased reducing capacity or the presence of abnormal hemoglobin, methemoglobinemia ensues. In most cases methemoglobinemia is transitory and of no major clinical consequence. Occasionally, however, it can be life threatening and must be rapidly diagnosed and treated. When methemoglobinemia is of hereditary nature, either due to deficiency of red cell NADH-methemoglobin reductase or due to the presence of M hemoglobin, it is a lifelong problem. Since most of these patients do not have major disabling symptoms, the treatment is aimed at correction of cyanosis.     

MnSOD overexpression prevents liver mitochondrial DNA depletion after an alcohol binge but worsens this effect after prolonged alcohol consumption in mice

Both acute and chronic alcohol consumption increase reactive oxygen species (ROS) formation and lipid peroxidation, whose products damage hepatic mitochondrial DNA (mtDNA). To test whether manganese superoxide dismutase (MnSOD) overexpression modulates acute and chronic alcohol-induced mtDNA lesions, transgenic MnSOD-overexpressing (TgMnSOD(+++)) mice and wild-type (WT) mice were treated by alcohol, either chronically (7 weeks in drinking water) or acutely (single intragastric dose of 5 g/kg). Acute alcohol administration increased mitochondrial ROS formation, decreased mitochondrial glutathione, depleted and damaged mtDNA, durably increased inducible nitric oxide synthase (NOS) expression, plasma nitrites/nitrates and the nitration of tyrosine residues in complex V proteins and decreased complex V activity in WT mice. These effects were prevented in TgMnSOD(+++) mice. In acutely alcoholized WT mice, mtDNA depletion was prevented by tempol, a superoxide scavenger, L-NAME and 1400W, two NOS inhibitors, or uric acid, a peroxynitrite scavenger. In contrast, chronic alcohol consumption decreased cytosolic glutathione and increased hepatic iron, lipid peroxidation products and respiratory complex I protein carbonyls only in ethanol-treated TgMnSOD(+++) mice but not in WT mice. In chronic ethanol-fed TgMnSOD(+++) mice, but not WT mice, mtDNA was damaged and depleted, and the iron chelator, deferoxamine (DFO), prevented this effect. In conclusion, MnSOD overexpression prevents mtDNA depletion after an acute alcohol binge but aggravates this effect after prolonged alcohol consumption, which selectively triggers iron accumulation in TgMnSOD(+++) mice but not in WT mice. In the model of acute alcohol binge, the protective effects of MnSOD, tempol, NOS inhibitors and uric acid suggested a role of the superoxide anion reacting with NO to form mtDNA-damaging peroxynitrite. In the model of prolonged ethanol consumption, the protective effects of DFO suggested the role of iron reacting with hydrogen peroxide to form mtDNA-damaging hydroxyl radical.     

Distinct gene expression profiles in subsets of chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B-cell receptors

Background

Numerous subsets of patients with chronic lymphocytic leukemia display similar immunoglobulin gene usage with almost identical complementarity determining region 3 sequences. Among IGHV4-34 cases, two such subsets with “stereotyped” B-cell receptors were recently identified, i.e. subset #4 (IGHV4-34/IGKV2-30) and subset #16 (IGHV4-34/IGKV3-20). Subset #4 patients appear to share biological and clinical features, e.g. young age at diagnosis and indolent disease, whereas little is known about subset #16 at a clinical level.

Design and Methods

We investigated the global gene expression pattern in sorted chronic lymphocytic leukemia cells from 25 subset/non-subset IGHV4-34 patients using Affymetrix gene expression arrays.

Results

Although generally few differences were found when comparing subset to non-subset 4/16 IGHV4-34 cases, distinct gene expression profiles were revealed for subset #4 versus subset #16. The differentially expressed genes, predominantly with lower expression in subset #4 patients, are involved in important cell regulatory pathways including cell-cycle control, proliferation and immune response, which may partly explain the low-proliferative disease observed in subset #4 patients.

Conclusions

Our novel data demonstrate distinct gene expression profiles among patients with stereotyped IGHV4-34 B-cell receptors, providing further evidence for biological differences in the pathogenesis of these subsets and underscoring the functional relevance of subset assignment based on B-cell receptor sequence features.     

Lethal Tuberculosis in a Previously Healthy Adult with IL-12 Receptor Deficiency

A 33-year-old man was admitted in hospital due to fever, generalized lymphadenopathy, and hepatosplenomegaly. He had a history of anti-tuberculosis treatment in the previous 3 years. Despite normal chest radiograph, a sputum sample was smear-positive for acid-fast bacilli, and polymerase chain reaction was positive for Mycobacterium tuberculosis complex. Drug susceptibility test revealed resistance to isoniazid and rifampin. Evaluation of the patient’s immune system revealed IL-12Rβ1 deficiency. The patient died of disseminated tuberculosis (TB), despite appropriate antibiotic treatment. This is the first IL-12 receptor-deficient patient presenting with disseminated TB in adulthood, without any previous relevant medical history. This diagnosis should be considered in selected adult patients with unexplained, overwhelming TB. IL-12Rβ1 deficiency is a genetic etiology of severe TB in adults and should be considered in adult patients with disseminated TB.     

Lesion area assessment in psoriasis patients

Psoriasis is an autoimmune skin disease, afflicting skin with red plaques that are usually accompanied by silvery-white scales. Various medical treatments are used, with different impacts on the patients, but there is no definite cure for the disease. The PASI standard is employed to measure the performance of the treatments. It includes four parameters, namely area, erythema, scaliness and skin thickness. The PASI parameters are usually measured manually by physicians through subjective clinical observations which are imprecise, time consuming and in some cases lead to diverse results. This paper presents a computer-based automatic method to measure the area parameter in the PASI standard. In the proposed method, the YCbCr colour space is used to differentiate the plaques from the skin by applying an optimal threshold method. Performance evaluation results indicate that the proposed method is able to determine lesion areas with accuracy higher than 96% for 18 out of 20 cases and higher than 92% for another case. As well as high accuracy the proposed method has another advantage over previous methods: it can automatically detect plaques with silvery-white scales, plaques on hairy skins and tiny plaques, as well as simple (scale-less) plaques.     

Study of programmed cell death 1 (PDCD1) gene polymorphims in Iranian patients with ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory disease, characterized by axial arthritis in which the genetic-environmental factors seem to be involved in the pathogenesis of the disease. This study was performed to investigate the role of polymorphisms of the programmed cell death 1 (PDCD1) gene on susceptibility to AS. In this study, 161 Iranian patients with AS and 208 normal controls were enrolled; two single-nucleotide polymorphisms (SNPs) of the PDCD1 gene PD-1.3 (G, A) in nucleotide position +7146 of intron 4 and PD-1.9 (C, T) in nucleotide +7625 of exon 5 were studied. Analysis of PD-1.3 revealed that 82% of patients and 79% of controls had GG genotype, while GA and AA genotypes were detected in 17% and 0.6% of patients, respectively, and 20% and 1.4% of controls, respectively. Moreover, the genotype CC (PD-1.9) was present in 92% of patients and 97% of controls. Although these differences were not statistically significant between patients and controls, comparisons of genotypes frequencies in the AS patients, based on human leukocyte antigen (HLA)-B27, revealed that all patients who had CT genotype (PD-1.9) were HLA-B27 positive, whereas 30% of patients with CC genotype were HLA-B27 negative. There was no evidence of association for PDCD1 SNPs with AS in our study, but CT genotype (PD-1.9) seems to be associated with HLA-B27 positivity in the patients with AS.     

Comparative Assessment of Antimicrobial Activities of Antibiotic-Treated Penile Prostheses

Background

Although infections associated with penile implants are relatively infrequent, they result in serious medical consequences. Because treatment of these infections usually requires removal of the infected penile implant, prevention of infection is crucial. Since bacterial colonization of the implant is a prelude to clinical infection, antimicrobial modification of the devices may inhibit device colonization and subsequent infection.

Objective

We compared the spectrum and durability, both in vitro and in vivo, of two antibiotic-treated penile prostheses: InhibiZone implants pre-impregnated with minocycline and rifampin (M/R) and Titan implants dipped in vancomycin.

Design, setting, and participants

1 × 1-cm cylinder segments of (1) control untreated, (2) M/R-impregnated, and (3) vancomycin-dipped implants were studied. Baseline zones of inhibition (ZI) were determined against clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant S. epidermidis (MRSE), vancomycin-resistant Enterococcus (VRE), and Escherichia coli. In addition, ZI against methicillin-susceptible S. aureus were compared both in vitro after being washed in a flow chamber and after subcutaneous implantation in rabbits for 1, 2, 7, and 14 d.

Measurements

ZI were measured as the diameter of the clear zone around each test device minus the external diameter of the device.

Results and limitations

Implants pre-impregnated with M/R displayed a broader spectrum of antimicrobial activity than vancomycin-dipped implants against both gram-positive and -negative bacteria. The M/R-impregnated devices also yielded significantly larger zones of inhibition against S. aureus than vancomycin-dipped implants, both in vitro (p < 0.003) and in vivo throughout the 14-d period of device implantation in rabbits (p ≤ 0.03).

Conclusions

Penile prostheses impregnated with M/R have a broader spectrum in vitro and a more durable antimicrobial activity in vitro and in an animal model than implants dipped in vancomycin. Therefore, along with being a more practical model for incorporating antimicrobials onto the device, the use of implants pre-impregnated with M/R may help reduce the incidence of penile implant infection.