A Study on the Prescription Pattern of Antimicrobial Agents Used in the Treatment of Infectious Disease

Antibiotics are anti-infective agents produced from natural sources, whereas antimicrobial agents are generated through chemical synthesis. It was a prospective and observational study and was conducted in the medicine, OBG, and urology departments in Sagar Hospitals. The study was conducted over a period of 18 to 20 months. Among 542 participants, 325 (60%) were males, while 217 (40%) were females. The frequency of patients surviving different hospital departments was 416 (76.6%), and they survived the medicine department. Moreover, the urology department had 80 (14.8%) patient visits, while in the obstetrics and gynaecology departments, only 46 (8.5%) patients visited. It was found that the percentage and order of various micro-organisms isolated as Neisseria meningitides 20 (3.7%) and a lesser number of organisms were found in K. Pneumonia 01 (0.2%), respectively. The cephalosporin class of drugs is commonly prescribed in empirical and prophylactic therapy because they are more effective in infectious diseases Furthermore, 36 patients out of 542 had drug interactions; quinoline derivatives, such as Ciprofloxacin, typically have a higher number of drug interactions. Among 542 patients, 38 had severe drug reactions in that most of the reactions were dermatological reactions caused by cephalosporin drugs. Most of our physicians prescribed based on patient characteristics and behaviors, and the recovery rate was also good. In our study, we observed common outcomes of DIs, such as increased theophylline toxicity and digoxin toxicity, increased laboratory values, and also reduced some drugs' effectiveness. Correlations of drug and disease characteristics were found more in ciprofloxacin drugs.

Enigma of Respiratory Carriage of Kingella kingae and Neisseria meningitides in Young Jordanian Children

Background: Kingella kingae and Neisseria meningitides are gram-negative bacteria, causing several life-threatening diseases and considered as opportunistic pathogens in the upper respiratory tract of healthy carriers. The detection of these both bacteria species is difficult in routine culture methods. Objective: This study aimed to find the occurrence rate of K. kingae and N. meningitides colonizing upper respiratory tract of young Jordanian children, and to determine the antimicrobial susceptibility profile of the isolates. Methods: A total of 300 samples of throat and nasal swabs were collected from out- patients Jordanian children aged between 6 months and 5 years, who were admitted to Pediatrics' clinics department at the Jordan University Hospital and Al-Bashir Hospital over the period October 2018 through January 2019. Samples were cultured for detection K. kingae and Neisseria species including specially N. meningitides. Their suspected growth was identified and tested using microbiology culture methods and polymerase chain reaction (PCR) method. Additionally, DNA was extracted directly from one 100 samples and was investigated only for K. kingae using real- time PCR assay. Results: This study showed the absence of K. kingae in all cultured samples, while Neisseriaspecies was detected in 21 (7 %)including one N. meningitides isolate(0.3%). The results of antibiotic susceptibility testing indicated presence of few percentage of Neisseria species isolates resistant 100 % to clindamycin, oxacillin and vancomycin, whereas all were susceptible for chloramphenicol (100%)levofloxacin and gentamycin , and less to ampicillin(90.6%) and erytromycin ( 85.7%), respectively. Conclusion: This study shows the absence of K. kingae and the rare occurrence of N. meningitides colonizing the upper respiratory tract of young Jordanian children over the 4-month period of study.

A novel design of multi-epitope peptide vaccine against Pseudomonas aeruginosa

Background: As an opportunistic pathogen, Pseudomonas aeruginosa causes many different hazardous infections. The high mortality rate resulting from infection with this antibiotic-resistant pathogen has made it a major challenge in clinical treatment; it has been listed as the most harmful bacterium to humans by the WHO. So far, no vaccine has been approved for P. aeruginosa. Objective: Infections performed by bacterial attachment and colonization with type IV pili (T4P), known as the most essential adhesive vital for adhesion, while pilQ is necessary for the biogenesis of T4P, also outer membrane proteins of a pathogen is also effective in stimulating the immune system; in this regard, pilQ, OprF, and OprI, are excellent candidate antigens for production of an effective vaccine against P. aeruginosa. Methods: In this research, various bioinformatics methods were employed in order to design a new multi-epitope peptide vaccine versus P. aeruginosa. Since T CD4+ cell immunity is important in eradicating P. aeruginosa, OprF, OprI, and pilQ antigens were analyzed to determineHelper T cell Lymphocyte (HTL) epitopes by many different immunoinformatics servers. One of the receptor agonists 2 (TLR2), a segment of the Por B protein from Neisseria meningitides was used as an adjuvant in order to stimulate an effective cellular immune response, and suitable linkers were used to connect all the above mentioned parts. In the vaccine construct, linear B cell epitopes were also identified. Results: Conforming the bioinformatics forecasts, the designed vaccine possesses high antigenicity and is not allergen. Conclusion: In this regard, the designed vaccine candidate is strongly believed to possess the potential of inducing cellular and humoral immunity against P. aeruginosa.

Simultaneous Immunization with Multiple Diverse Immunogens Alters Development of Antigen-Specific Antibody-Mediated Immunity

Vaccination remains one of the most successful medical interventions in history, significantly decreasing morbidity and mortality associated with, or even eradicating, numerous infectious diseases. Although traditional immunization strategies have recently proven insufficient in the face of many highly mutable and emerging pathogens, modern strategies aim to rationally engineer a single antigen or cocktail of antigens to generate a focused, protective immune response. However, the effect of cocktail vaccination (simultaneous immunization with multiple immunogens) on the antibody response to each individual antigen within the combination, remains largely unstudied. To investigate whether immunization with a cocktail of diverse antigens would result in decreased antibody titer against each unique antigen in the cocktail compared to immunization with each antigen alone, we immunized mice with surface proteins from uropathogenic Escherichia coli, Mycobacterium tuberculosis, and Neisseria meningitides, and monitored the development of antigen-specific IgG antibody responses. We found that antigen-specific endpoint antibody titers were comparable across immunization groups by study conclusion (day 70). Further, we discovered that although cocktail-immunized mice initially elicited more robust antibody responses, the rate of titer development decreases significantly over time compared to single antigen-immunized mice. Investigating the basic properties that govern the development of antigen-specific antibody responses will help inform the design of future combination immunization regimens.

Current Update on Intrinsic and Acquired Colistin Resistance Mechanisms in Bacteria

Colistin regained global interest as a consequence of the rising prevalence of multidrug-resistant Gram-negative Enterobacteriaceae. In parallel, colistin-resistant bacteria emerged in response to the unregulated use of this antibiotic. However, some Gram-negative species are intrinsically resistant to colistin activity, such as Neisseria meningitides, Burkholderia species, and Proteus mirabilis. Most identified colistin resistance usually involves modulation of lipid A that decreases or removes early charge-based interaction with colistin through up-regulation of multistep capsular polysaccharide expression. The membrane modifications occur by the addition of cationic phosphoethanolamine (pEtN) or 4-amino-l-arabinose on lipid A that results in decrease in the negative charge on the bacterial surface. Therefore, electrostatic interaction between polycationic colistin and lipopolysaccharide (LPS) is halted. It has been reported that these modifications on the bacterial surface occur due to overexpression of chromosomally mediated two-component system genes (PmrAB and PhoPQ) and mutation in lipid A biosynthesis genes that result in loss of the ability to produce lipid A and consequently LPS chain, thereafter recently identified variants of plasmid-borne genes (mcr-1 to mcr-10). It was hypothesized that mcr genes derived from intrinsically resistant environmental bacteria that carried chromosomal pmrC gene, a part of the pmrCAB operon, code three proteins viz. pEtN response regulator PmrA, sensor kinase protein PmrAB, and phosphotransferase PmrC. These plasmid-borne mcr genes become a serious concern as they assist in the dissemination of colistin resistance to other pathogenic bacteria. This review presents the progress of multiple strategies of colistin resistance mechanisms in bacteria, mainly focusing on surface changes of the outer membrane LPS structure and other resistance genetic determinants. New handier and versatile methods have been discussed for rapid detection of colistin resistance determinants and the latest approaches to revert colistin resistance that include the use of new drugs, drug combinations and inhibitors. Indeed, more investigations are required to identify the exact role of different colistin resistance determinants that will aid in developing new less toxic and potent drugs to treat bacterial infections. Therefore, colistin resistance should be considered a severe medical issue requiring multisectoral research with proper surveillance and suitable monitoring systems to report the dissemination rate of these resistant genes.

The Position of EGF Deprivation in the Management of Advanced Non-Small Cell Lung Cancer

Advanced non-small cell lung cancer (NSCLC) has faced a therapeutic revolution with the advent of tyrosine kinase inhibitors (TKIs) and immune checkpoints inhibitors (ICIs) approved for first and subsequent therapies. CIMAvax-EGF is a chemical conjugate between human-recombinant EGF and P64, a recombinant protein from Neisseria meningitides, which induces neutralizing antibodies against EGF. In the last 15 years, it has been extensively evaluated in advanced NSCLC patients. CIMAvax-EGF is safe, even after extended use, and able to keep EGF serum concentration below detectable levels. In a randomized phase III study, CIMAvax-EGF increased median overall survival of advanced NSCLC patients with at least stable disease after front-line chemotherapy. Patients bearing squamous-cell or adenocarcinomas and serum EGF concentration above 870 pg/ml had better survival compared to control patients treated with best supportive care as maintenance, confirming tumors’ sensitivity to the EGF depletion. This manuscript reviews the state-of-the-art NSCLC therapy and proposes the most promising scenarios for evaluating CIMAvax-EGF, particularly in combination with TKIs or ICIs. We hypothesize that the optimal combination of CIMAvax-EGF with established therapies can further contribute to transform advanced cancer into a manageable chronic disease, compatible with years of good quality of life.

Clinical features and management strategies of Meningitis in adult patients: A hospital based study from Kuwait

Introduction: High mortality rate of meningitis has been reported in Kuwait, however, limited data is available describing this disease in adult patients. With this background, we conducted a prospective study on patients admitted with meningitis, with an objective to describe the risk factors, clinical presentation, disease course and outcome; focus given on diagnostic problems and consequent management difficulties. Methods: Our team diagnosed, managed and documented hospital records of patients (n=44) admitted with suspected meningitis at a referral hospital during 2010-12. Detailed information was collected regarding clinical presentation, CSF analysis, treatment, hospital course and outcome as per Glasgow Outcome Scale (GOS). Results: Bacterial, viral, and tuberculosis (TB) meningitis were seen in 22.8%, 52.3%, and 15.9% of patients. Clinical features of our cohort were consistent with available literature. Positive identification of organism by culture, gram stain, or antigen test was possible in only 6 patients i.e. Streptococcus pneumonae-(n=3), Streptococcus agalactiae-(n=2), Neisseria meningitides-(n=1). CSF polymerase chain reaction was detected positive for Enterovirus RNA, and Herpes simplex virus DNA for one patient each. Empirical antimicrobial treatment directed against common causative organisms was the mainstay of management of bacterial meningitis. Viral meningitis was managed symptomatically. TB meningitis patients were administered anti-tubercular treatment. As per GOS, 38(85.4%) patients recovered with no neurological deficit. Six patients recovered with mild to moderate deficit. Conclusion: Low positive culture rates and inability to identify pathogens have been a diagnostic challenge faced by our team. Strong clinical suspicion, early empiric antibiotic and dexamethasone therapy perhaps contributed to very good recovery in our study. Keywords: Meningitis, Kuwait, Clinical Suspicion, Antibiotic, Dexamethasone

Microbial aspects and potential markers for differentiation between bacterial and viral meningitis among adult patients

Objectives Meningitis is a medical emergency with permanent disabilities and high mortality worldwide. We aimed to determine causative microorganisms and potential markers for differentiation between bacterial and viral meningitis. Methodology Adult patients with acute meningitis were subjected to lumber puncture. Cerebrospinal fluid (CSF) microorganisms were identified using Real-time PCR. PCT and CRP levels, peripheral and CSF-leucocyte count, CSF-protein and CSF-glucose levels were assessed. Results Out of 80 patients, infectious meningitis was confirmed in 75 cases; 38 cases were bacterial meningitis, 34 cases were viral meningitis and three cases were mixed infection. Higher PCT, peripheral and CSF-leukocytosis, higher CSF-protein and lower CSF-glucose levels were more significant in bacterial than viral meningitis patients. Neisseria meningitides was the most frequent bacteria and varicella-zoster virus was the most common virus. Using ROC analyses, serum PCT and CSF-parameters can discriminate bacterial from viral meningitis. Combined ROC analyses of PCT and CSF-protein significantly improved the effectiveness in predicting bacterial meningitis (AUC of 0.998, 100%sensitivity and 97.1%specificity) than each parameter alone (AUC of 0.951 for PCT and 0.996 for CSF-protein). Conclusion CSF-protein and serum PCT are considered as potential markers for differentiating bacterial from viral meningitis and their combination improved their predictive accuracy to bacterial meningitis.