Number Of Bacterial Infections Research Articles

Diagnostic performance of procalcitonin for bacterial infection in severe alcoholic hepatitis compared with C-reactive protein

BackgroundSevere alcoholic hepatitis is a catastrophic disease with a mortality rate of up to 35–50% at 30 days. Bacterial infection is an important prognostic factor in patients with severe alcoholic hepatitis, but it is difficult to detect the presence of infection immediately. Procalcitonin (PCT) is a well-known inflammatory marker that can detect bacterial infections in various diseases early. Therefore, we aimed to evaluate the diagnostic accuracy of PCT for bacterial infection in severe alcoholic hepatitis.MethodsWe prospectively enrolled patients with severe alcoholic hepatitis, defined as modified Maddrey’s Discriminant Function ≥ 32, from 10 medical centers. At admission, we performed an initial evaluation including physical examination, laboratory test, radiology, blood and urine culture, PCT, and C-reactive protein (CRP). We compared the receiver operating characteristic (ROC) curves of PCT and CRP for bacterial infection, systemic inflammatory response syndrome (SIRS), and sepsis among total patients.ResultsA total of 108 patients with severe alcoholic hepatitis were enrolled. The number of bacterial infections, SIRS, and sepsis were 31 (28.7%), 41 (38.0%), and 19 (17.6%), respectively. The patients with bacterial infection had significantly higher MELD scores (24.0 vs. 15.0), PCT levels (1.5 vs. 0.4 ng/mL), and CRP levels (4.9 vs. 2.5 mg/dL) compared to those without bacterial infection. The area under the ROC curve (AUROC) of PCT vs. CRP for bacterial infection was 0.752 and 0.655, respectively (P = 0.113). The AUROC of PCT vs. CRP for SIRS was 0.699 and 0.662, respectively (P = 0.490). The AUROC of PCT vs. CRP for sepsis was 0.780 and 0.630, respectively (P = 0.027).ConclusionsAmong patients with severe alcoholic hepatitis, PCT showed a trend of superior diagnostic performance in the early detection of bacterial infection and sepsis compared to CRP. Although PCT might have better potential to diagnose sepsis in the setting of severe alcoholic hepatitis, it is necessary to find more reliable diagnostic markers.

The Role of Biofilms in the Pathogenesis of Animal Bacterial Infections.

Biofilms are bacterial aggregates embedded in a self-produced, protective matrix. The biofilm lifestyle offers resilience to external threats such as the immune system, antimicrobials, and other treatments. It is therefore not surprising that biofilms have been observed to be present in a number of bacterial infections. This review describes biofilm-associated bacterial infections in most body systems of husbandry animals, including fish, as well as in sport and companion animals. The biofilms have been observed in the auditory, cardiovascular, central nervous, digestive, integumentary, reproductive, respiratory, urinary, and visual system. A number of potential roles that biofilms can play in disease pathogenesis are also described. Biofilms can induce or regulate local inflammation. For some bacterial species, biofilms appear to facilitate intracellular invasion. Biofilms can also obstruct the healing process by acting as a physical barrier. The long-term protection of bacteria in biofilms can contribute to chronic subclinical infections, Furthermore, a biofilm already present may be used by other pathogens to avoid elimination by the immune system. This review shows the importance of acknowledging the role of biofilms in animal bacterial infections, as this influences both diagnostic procedures and treatment.

Activities of Eravacycline, Tedizolid, Norvancomycin, Nemonoxacin, Ceftaroline, and Comparators against 1,871 Staphylococcus and 1,068 Enterococcus Species Isolates from China: Updated Report of the CHINET Study 2019.

To evaluate the in vitro activities of eravacycline, tedizolid, nemonoxacin, norvancomycin, and ceftaroline against Staphylococcus and Enterococcus species isolates were collected as part of the China Antimicrobial Surveillance Network (CHINET) in 2019 to provide susceptibility data for Staphylococcus spp. and Enterococcus spp. for their future development and application in clinical practice. Antimicrobial susceptibility testing was performed using the CLSI broth microdilution reference method. Eravacycline was highly active against Staphylococcus and Enterococcus species isolates, proved by the MIC50/90: 0.06/0.125, 0.06/0.25, 0.06/0.25, 0.06/0.25, 0.125/0.5, 0.125/0.25, and 0.03/0.06 mg/L for Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), S. epidermidis, S. hominis, S. haemolyticus, Enterococcus faecalis, and E. faecium, respectively. S. aureus isolates tested were fully susceptible to tedizolid. Still, nonsusceptible isolates were found for E. faecalis (72/567 [12.7%]) and E. faecium (12/501 [2.4%]). Norvancomycin at 2 mg/L could inhibit 100% of Staphylococcus spp., while 1 mg/L of ceftaroline could inhibit 78.9% of MRSA and 99.9% of methicillin-susceptible S. aureus (MSSA) isolates. Additionally, nemonoxacin was also active against Staphylococcus and Enterococcus species isolates tested (shown by the following MIC90s and ranges, in milligrams per liter: 2 and ≤0.015 to 8 for MRSA, 0.25 and ≤0.015 to 4 for MSSA, 0.5 and ≤0.015 to 8 for S. epidermidis, and 4 and ≤0.015 to >32 for E. faecalis). In conclusion, both eravacycline and tedizolid were highly active against clinical isolates of Staphylococcus spp. and Enterococcus spp. recently collected across China. Nemonoxacin showed potent activity against Staphylococcus spp. and E. faecalis but limited activity against E. faecium. Norvancomycin and ceftaroline displayed highly potent activity against Staphylococcus spp. IMPORTANCE Antimicrobial resistance has become a severe threat to global public health. According to statistics, nearly 700,000 people die from bacterial infections worldwide (J. O'Neill, Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations, 2014; C. Y. Chin, K. A. Tipton, M. Farokhyfar, E. M. Burd, et al., Nat Microbiol 3:563-569, 2018, https://doi.org/10.1038/s41564-018-0151-5). The number of bacterial infections is expected to climb to 10 million by 2050, showing that bacterial resistance has become a significant problem that cannot be ignored. It is crucial to develop new antimicrobial agents to combat antimicrobial-resistant bacteria. In this study, we evaluated the in vitro activities of eravacycline, tedizolid, nemonoxacin, norvancomycin, and ceftaroline against Staphylococcus spp. and Enterococcus species isolates which were collected as part of CHINET in 2019. We believe that this study can provide susceptibility data for Staphylococcus spp. and Enterococcus spp. for their future development and application in clinical practice.

638P Burden of infection in patients with multiple myeloma and secondary immunodeficiencies: A retrospective cohort study

This study aimed to provide insights into the burden of infection in patients with multiple myeloma (MM) with or without secondary immunodeficiencies (SID). In this retrospective cohort study, data were extracted from the Optum-Humedica electronic record database during the period 01-Oct-2015 to 10-Mar-2020, which included a 6-month pre-index period (PIP) and 12-month follow-up following patient identification. Patients aged ≥18 years with a confirmed diagnosis of MM in the PIP were included in the analysis and stratified into two cohorts: those with (SID cohort) and those without SID (no-SID cohort). If a patient had SID or primary immunodeficiencies in the PIP, they were excluded. The first occurrence of a hypogammaglobulinemia ICD-10 code, or a low (<5.0 g/L) serum Immunoglobulin G level was defined as the SID index date. Of patients with MM, 870 with SID and 3768 without SID were included (mean age: 66.5 and 68.7 years; males: 54.3% and 53.6%; respectively). At 12-month follow-up, significantly more patients in the SID cohort experienced ≥1 infection than the no-SID cohort (58.9% vs 32.1%, p<0.001). A similar pattern was observed for mean number of infections, patients experiencing ≥1 severe bacterial infection or ≥1 infection-associated hospitalization (Table). The most common infection in both cohorts was bacterial: SID, mean (standard deviation [SD]) number of bacterial infections 6.83 (8.04) and no-SID, 4.73 (6.57), p<0.001. Kaplan–Meier analysis showed overall survival (OS) at 24 months was lower in the SID cohort (74.9% of patients alive) than the no-SID cohort (81.8%).Table: 638POutcome measures at 12 monthsSID n=870No-SID n=3768p value SID vs no-SIDNumber of infections, mean (SD)7.07 (9.23)4.58 (6.45)<0.001Patients with ≥1 severe bacterial infection,a n (%)276 (31.7)510 (13.5)<0.001Patients with ≥1 hospitalization associated with any infection, n (%)231 (26.6)350 (9.3)<0.001Number of hospitalizations, mean (SD)6.55 (8.65)5.47 (6.90)0.11Length of hospital stay, mean (SD), days13.02 (34.95)9.69 (26.88)0.22aDefined using ICD-10 codes for bacteremia or sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia and visceral abscess. Open table in a new tab aDefined using ICD-10 codes for bacteremia or sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia and visceral abscess. Patients with MM and SID have a substantially higher burden of infection and healthcare resource use, and lower OS than those without SID. Understanding this burden will allow for earlier targeted treatment of individuals at risk of SID. Study/medical writing support funder: Takeda Development Center Americas, Inc.

Characterization of anti-microbial peptides and proteins from maggots of Calliphoridae and Sarcophagidae fly species (Diptera)

Removal of infected wounds using maggots has been known for centuries. Early research has shown that the maggot exosecretion, whole body, and fecal waste products of Calliphoridae and Sarcophagidae species contain a variety of alkaline peptides capable of inhibiting bacterial growth. Since the wide application of antibiotics such as penicillin, a number of bacterial infections have become insensitive to antibiotic treatment. In many of these instances, maggot therapy has been successfully applied for the treatment of chronic wounds. To identify and compare the expression patterns of anti-microbial peptides (AMPs) from some dipteran species, transcriptome analyses were conducted for the maggots of 11 Calliphoridae and Sarcophagidae species. Species of the subfamily Calliphorinae showed relatively higher expression levels of AMPs and anti-microbial proteins compared with those of Luciliinae and Sarcophagidae species. Furthermore, among all of the dipteran species examined, Lucilia illustris exhibited the highest transcription levels of AMPs. Cecropin A2 and defensin, whose expression levels were the highest among the anti-microbial peptides, were synthesized to test their biological activity. The synthesized peptides showed anti-microbial activities without hemolytic activities. In particular, cecropin A2 of L. illustris exhibited the highest anti-microbial activity against all of the bacteria and fungi examined, thereby possessing the potential to be developed as a new alternative to antibiotics. This comparative transcriptomic study may provide new insights into anti-microbial compositions of some dipteran species.

Antimicrobial properties of common household spices on microbes cultured from two kitchen locations

The number of bacterial infections in humans is rising, and a major contributor is foodborne illnesses, which affect a large portion of the population and result in many hospitalizations and deaths. Common household cleaners are an effective strategy to combat foodborne illness, but they are often costly and contain harmful chemicals. Thus, we sought to test the antimicrobial effectiveness of readily available, low cost, and relatively harmless spices (clove, nutmeg, astragalus, cinnamon, turmeric, and garlic) on microbes cultured from refrigerator handles and cutting boards. We hypothesized that cutting boards would have microbes that were more resistant to spices given the properties that make them conducive to microbial growth, whereas the microbes cultured from refrigerator handles would be more prone to the antimicrobial effects of the spices. We found that clove, garlic, and nutmeg were able to completely prevent the growth of microbes from cutting boards. Clove and garlic also prevented microbial growth from refrigerator handle samples, but nutmeg only reduced the growth of these microbes over a week. Similarly, turmeric and cinnamon only reduced the growth of microbes over a week from both culture samples. Our results demonstrate long-lasting, antimicrobial effects of multiple spices that support their use as alternatives to common household cleaners.

In vivo study on the effects of intercellular adhesion operon of Staphylococcus epidermidis on the inflammation associated with bacteria-fungal mixed biofilm

To study the effect of intercellular adhesion (ica) operon of Staphylococcus epidermidis on the inflammation associated with mixed biofilm of Staphylococcus epidermidis and Candida albicans on endotracheal tube material in rabbits. The standard strains of Staphylococcus epidermidis RP62A (ica operon positive, positive group) and ATCC12228 (ica operon negative, negative group) were taken to prepare a bacterial solution with a concentration of 1×10 6 CFU/mL, respectively. Then, the two bacterial solutions were mixed with the standard strain of Candida albicans ATCC10231 of the same concentration to prepare a mixed culture solution at a ratio of 1∶1, respectively. The mixed culture solution was incubated with endotracheal tube material for 24 hours. The formation of mixed biofilm on the surface of the material was observed by scanning electron microscope. Thirty New Zealand rabbits, aged 4-6 months, were divided into two groups ( n=15), and the endotracheal tube materials of the positive group and the negative group that were incubated for 24 hours were implanted beside the trachea. The body mass of rabbits in the two groups was measured before operation and at 1, 3, and 7 days after operation. At 1, 3, and 7 days after operation, the levels of interleukin 1β (IL-1β), IL-6, tumor necrosis factor α (TNF-α), and monocytechemotactic protein 1 (MCP-1) were detected by using an ELISA test kit. At 7 days after operation, the formation of mixed biofilm on the surface of the endotracheal tube materials was observed by scanning electron microscope, the inflammation and infiltration of tissues around the materials were observed by HE staining, and the bacterial infections in heart, lung, liver, and kidney were observed by plate colony counting method. Scanning electron microscope observation showed that the mixed biofilm structure was obvious in the positive group after 24 hours in vitro incubation, but no mixed biofilm formation was observed in the negative group. In vivo studies showed that there was no significant difference in body mass between the two groups before operation and at 1, 3, and 7 days after operation ( P>0.05). Compared with the negative group, the levels of MCP-1 and IL-1β at 1 day, and the levels of IL-1β, MCP-1, IL-6, and TNF-α at 3 and 7 days in the positive group all increased, with significant differences ( P<0.05). Scanning electron microscope observation showed that a large amount of Staphylococcus epidermis and mixed biofilm structure were observed in the positive group, and a very small amount of bacteria was observed in the negative group with no mixed biofilm structure. HE staining of surrounding tissue showed inflammatory cell infiltration in both groups, and neutrophils and lymphocytes were more in the positive group than in the negative group. There was no significant difference in the number of bacterial infections in heart and liver between the two groups ( P>0.05). The number of bacterial infections in lung and kidney in the positive group was higher than that in negative group ( P<0.05). In the mixed infection of Staphylococcus epidermidis and Candida albicans, the ica operon may strengthen the structure of the biofilm and the spread of the biofilm in vivo, leading to increased inflammatory factors, and the bacteria are difficult to remove and persist.

Observational case studies of treatment of skin disorders with natural phages in Ganga water

Background: Skin conditions have multiple causes. Natural phages in the Ganga River have bactericidal qualities against a number of bacterial infections, which help resolve skin conditions. Materials and Methods: We collected water from upper reaches of the Ganga River where the number of isolates of phages was more than 200 according to a study of the National Environmental Engineering Institute, Nagpur. The water was collected in May 2020 before the onset of monsoons and stored with sediments so that the phages adsorbed in the sediments cleaned up the overlaying column of water of all coliforms. We supplied the water by post to a number of volunteers who took the water through oral, topical or nasal route as per their convenience. Thirty-nine of the 52 volunteers provided data by telephone on their skin conditions on which this study is based. Results: The results show that an improvement of 1.7 on Likert Scale of 1-10 is obtained on skin conditions as per assessment of the volunteers after a treatment of 100 days. Further improvement of 1.0 on Likert Scale was reported after 85 days of stoppage of treatment. Conclusions: Natural phages of Ganga river could provide an inexpensive treatment not only for skin conditions but other comorbidities as well because skin conditions have multiple causes and phages of Ganga water may work at multiple levels.

Growing emergence of drug-resistant Pseudomonas aeruginosa and attenuation of its virulence using quorum sensing inhibitors: A critical review.

A perilous increase in the number of bacterial infections has led to developing throngs of antibiotics for increasing the quality and expectancy of life. Pseudomonas aeruginosa is becoming resistant to all known conventional antimicrobial agents thereby posing a deadly threat to the human population. Nowadays, targeting virulence traits of infectious agents is an alternative approach to antimicrobials that is gaining much popularity to fight antimicrobial resistance. Quorum sensing (QS) involves interspecies communication via a chemical signaling pathway. Under this mechanism, cells work in a concerted manner, communicate with each other with the help of signaling molecules called auto-inducers (AI). The virulence of these strains is driven by genes, whose expression is regulated by AI, which in turn acts as transcriptional activators. Moreover, the problem of antibiotic-resistance in case of infections caused by P. aeruginosa becomes more alarming among immune-compromised patients, where the infectious agents easily take over the cellular machinery of the host while hidden in the QS mediated biofilms. Inhibition of the QS circuit of P. aeruginosa by targeting various signaling pathways such as LasR, RhlR, Pqs, and QScR transcriptional proteins will help in blocking downstream signal transducers which could result in reducing the bacterial virulence. The anti-virulence agent does not pose an immediate selective pressure on growing bacterium and thus reduces the pathogenicity without harming the target species. Here, we review exclusively, the growing emergence of multi-drug resistant (MDR) P. aeruginosa and the critical literature survey of QS inhibitors with their potential application of blocking P. aeruginosa infections.

Structural Characterization and Isotopic Abundance Ratio Analysis of the Consciousness Energy Healing Treated Ofloxacin

Ofloxacin is an antibiotic, useful against the number of bacterial infections. This scientific investigation was performed to identify the impact of the Trivedi Effect®-Consciousness Energy Healing Treatment on the structural properties and the isotopic abundance ratio of ofloxacin using sophisticated analytical techniques. Ofloxacin sample was divided into control and treated parts. Only the treated ofloxacin received the Consciousness Energy Healing Treatment remotely by a well-known Biofield Energy Healer, Mr. Mahendra Kumar Trivedi. The LC-MS spectra of both the samples of ofloxacin at retention time 3 minutes exhibited the mass of the protonated molecular ion peak at m/z 362.17 (M+H)+. The chromatographic peak area% of the treated ofloxacin (52.4%) was increased by 2.03% compared to the control sample (51.36%). The LC-MS based isotopic abundance ratio of PM+1/PM in the Biofield Treated ofloxacin was significantly increased by 22.43% compared with the control sample. Similarly, the GC-MS based isotopic abundance ratio of PM+1/PM in the Biofield Treated ofloxacin was significantly increased by 19.24% compared with the control sample. The LC-MS and GC-MS based isotopic abundance ratio of PM+1/PM (2H/1H or 15N/14N or 13C/12C or 17O/16O) was significantly increased in the Biofield Treated ofloxacin as compared to the control sample. Thus,2H, 15N, 13C, and17O contributions from (C18H21FN3O4)+ to m/z 363.17 in the treated ofloxacin were significantly increased compared with the control sample. The increased isotopic abundance ratio of the Trivedi Effect®-Consciousness Energy Healing Treated ofloxacin may increase the intra-atomic bond strength and increase its physical stability. The new form of treated ofloxacin would be more stable, better soluble, and bioavailable compared to the control sample. It would be more useful to design efficacious pharmaceutical formulations that might offer better therapeutic response against infections in the urethra, urinary tract, gonorrhoea, pneumonia, infectious diarrhoea, bronchitis, cellulitis, bacterial infection of the eye and ear, multidrug-resistant tuberculosis, prostatitis, otitis media, plague, etc.

Insect Ultra-Structures as Effective Physical-Based Bactericidal Surfaces

Bacteria colonization of substrates is a key issue threatening the health of humans worldwide. This review summarized recent bactericidal activity evidence of different structures developed by insects. We evaluated different mechanisms in bactericidal activity among several insect species, and we also provided a glimpse at attempts at fabricating bactericidal bioinspired structures. In addition, we investigated the link between species with mechano-bactericidal surfaces and their evolution and ecological dynamics. It emerged that mostly hemimetabolous insects evolved bactericidal nanostructures on their wings, probably due to development of their wings externally during postembryonal development. Whereas, holometabolous insects, which develop their wings internally during metamorphosis, have their wings exposed to the environment just in the adult instar, and thus subjected to bacteria for a shorter period compared to hemimetabolous insects. Bio-inspired high-aspect-ratio nanopillared surfaces with bactericidal properties might broaden the application area of bactericidal surfaces, to mechanically decrease the number of bacterial infections.

Osteomyelitis complicating secondarily infected atopic eczema: two case reports and a narrative literature review

BackgroundAtopic eczema is a relapsing, itchy chronic cutaneous inflammatory disease that commonly affects children. The disease is often complicated by cutaneous infections such as eczema herpeticum, eczema vaccinatum and a varied number of bacterial infections – impetigo, cellulitis and erysipelas. However, rare case reports of infective endocarditis, otitis media and osteo-articular infections have been associated with atopic eczema. These associations possibly represent the extracutaneous infectious complications of atopic eczema.Case presentationHere we present two cases of osteomyelitis in HIV negative children with habitual scratching of poorly managed and/or uncontrolled atopic eczema respectively. Both cases presented to the orthopaedic surgeons and were admitted as acute phalangeal osteomyelitis and acute – on – chronic tibial osteomyelitis respectively. The first case was an 8 year old girl who had moderate-severe poorly-controlled atopic eczema and contiguously spread phalangeal osteomyelitis. The second case was an 11 year old pre-pubertal boy who had untreated atopic eczema and tibial osteomyelitis possibly from haematogenously spread Staphylococcus aureus infection. Both were successfully discharged from hospital and currently have well controlled eczema. The 11 year old patient is also being reviewed monthly by the orthopaedic surgeons and is chronic suppressive antibiotics. He may require sequestrectomy, should it be needed.ConclusionsInvasive staphylococcal and streptococcal osteo-articular (OA) infection can arise as an extra-cutaneous infectious complication of poorly controlled atopic eczema. It is more common in the 3 to 15 year age group and especially in boys with a septic arthritis to osteomyelitis ratio of around 29:5. Clinicians should maintain a high index of suspicion in patients with moderate-severe atopic eczema and they ought to promptly manage these OA infections with intravenous antibiotics to avoid further complications.

Changes in blood chemistry values of the cattle with associative course of leukemia and brucellosis

This paper describes the results obtained when the characteristics of metabolic process changes in leukemia, including brucellosis-complicated leukemia, were studied. To do it, 50 blood serum samples were taken from cows with specific antibodies against bovine leukemia virus (BLV) under the results of immunological diffusion reactions (IDR), indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA). All samples were serologically tested to detect a number of bacterial infections resulted in a possibility to establish that the BLV carrier state in most animals is combined with a bacterial infection, especially brucellosis (46%), chlamydia (20%), paratuberculosis (12%) and campylobacteriosis (8 %). At the next stage, 3 groups of 10 animals each were formed to study the metabolic process level, i.e. clinical healthy animals with no specific antibodies revealed during diagnostic tests for leukemia and other infections (Group 1); BLV carriers (Group 2); brucellosisand virus carrier animals (Group 3). Analysis of the blood chemistry values obtained for the experimental groups showed an uneven path of changes, especially for the protein and fat metabolism parameters. The difference was in albumin and cholesterol concentrations reduced in BLV infected animals, while their level was significantly increased in animals with leukemia associated with brucellosis, on the contrary.

Exploring the "Multiple-Hit Hypothesis" of Neurodegenerative Disease: Bacterial Infection Comes Up to Bat.

Despite major strides in personalized genomics, it remains poorly understood why neurodegenerative diseases occur in only a fraction of individuals with a genetic predisposition and conversely, why individuals with no genetic risk of a disorder develop one. Chronic diseases like Alzheimer's, Parkinson's, and Multiple sclerosis are speculated to result from a combination of genetic and environmental factors, a concept commonly referred to as the “multiple hit hypothesis.” A number of bacterial infections have been linked to increased risk of neurodegeneration, and in some cases, clearance of bacterial pathogens has been correlated with amelioration of central nervous system (CNS) deficits. Additionally, mutations in several genes known to contribute to CNS disorders like Parkinson's Disease have repeatedly been implicated in susceptibility to intracellular bacterial infection. Recent data has begun to demonstrate roles for these genes (PARK2, PINK1, and LRRK2) in modulating innate immune outcomes, suggesting that immune dysregulation may play an even more important role in neurodegeneration than previously appreciated. This review will broadly explore the connections between bacterial infection, immune dysregulation, and CNS disorders. Understanding this interplay and how bacterial pathogenesis contributes to the “multiple-hit hypothesis” of neurodegeneration will be crucial to develop therapeutics to effectively treat both neurodegeneration and infection.

In vitro quality evaluation of leading brands of ciprofloxacin tablets available in Bangladesh

BackgroundCiprofloxacin is a broad-spectrum antibiotic that acts against a number of bacterial infections. The study was carried out to examine the in vitro quality control tests for ten leading brands of ciprofloxacin hydrochloride 500 mg tablet formulation, registered in Bangladesh by Directorate General of Drug Administration. The quality control parameters of ten different brands of ciprofloxacin hydrochloride 500 mg tablets were determined by weight variation, friability, hardness, disintegration, dissolution and assay tests. All the tablets were evaluated for conformity with United States Pharmacopoeia-National Formulary (USP-NF) and British Pharmacopoeia (BP) standards.ResultsAmong ten brands of tablets Brand C had lower mean weight variation of 1.59% and Brand E had highest mean weight variation of 3.32%. For friability test Brand F had lowest mean friability (0.27%) and Brand G had highest mean friability (0.54%). Among ten brands mean lowest and highest hardness were founded in Brand G (4.49 kg/cm2) and Brand F (7.13 kg/cm2) respectively. The disintegration time for ten brands of ciprofloxacin tablet obtained were in the subsequent order: Brand G (8.19 min) < Brand C (9.25 min) < Brand E (9.61 min) < Brand D (10.11 min) < Brand B (11.07 min) < Brand A (12.15 min) < Brand H (13.68 min) < Brand I (14.59 min) < Brand J (16.32 min) < Brand F (17.49 min). Among ten brands for dissolution test mean percentages of drug release were not less than 80% in 45 min for four tablets (Brand E, 81.52%; Brand D, 86.44%; Brand G, 86.82% and Brand C, 94.12%), consequently they met BP standard and as per USP-NF standard six brands (Brand B, 75.62%; Brand A, 76.18%; Brand E, 81.52%; Brand D, 86.44%; Brand G, 86.82% and Brand C, 94.12%) had released not less than 75% drugs, so they also complied with the standard. The percentages of the drug content of the ten brands of ciprofloxacin tablet were obtained in the following sequence: Brand H (96.84%) < Brand J (97.34%) < Brand D (98.15%) < Brand I (98.47%) < Brand E (99.37%) < Brand F (100.28%) < Brand B (100.38%) < Brand A (100.54%) < Brand G (101.39%) < Brand C (101.46%). All of the brands met the BP and USP-NF specifications for assay. First-order, Higuchi and Korsmeyer–Peppas kinetics model fit for all of the mentioned ten brands.ConclusionThe present study revealed that all of the leading brands of this tablet met the quality control parameters as per pharmacopoeial specifications except dissolution test for four brands (Brand J, Brand H, Brand I, and Brand F).

Intravenous immunoglobulin for hypogammaglobulinemia after lung transplantation: a randomized crossover trial.

BackgroundWe aimed to determine the effects of treatment with intravenous immunoglobulin on bacterial infections in patients with hypogammaglobulinemia (HGG) after lung transplantation.MethodsWe performed a randomized, double-blind, placebo-controlled two-period crossover trial of immune globulin intravenous (IVIG), 10% Purified (Gamunex, Bayer, Elkhart, IN) monthly in eleven adults who had undergone lung transplantation more than three months previously. We randomized study participants to three doses of IVIG (or 0.1% albumin solution (placebo)) given four weeks apart followed by a twelve week washout and then three doses of placebo (or IVIG). The primary outcome was the number of bacterial infections within each treatment period.ResultsIVIG had no effect on the number of bacterial infections during the treatment period (3 during IVIG and 1 during placebo; odds ratio 3.5, 95% confidence interval 0.4 to 27.6, p = 0.24). There were no effects on other infections, use of antibiotics, or lung function. IVIG significantly increased trough IgG levels at all time points (least square means, 765.3 mg/dl during IVIG and 486.3 mg/dl during placebo, p<0.001). Four serious adverse events (resulting in hospitalization) occurred during the treatment periods (3 during active treatment and 1 during the placebo period, p = 0.37). Chills, flushing, and nausea occurred during one infusion of IVIG.ConclusionsTreatment with IVIG did not reduce the short-term risk of bacterial infection in patients with HGG after lung transplantation. The clinical efficacy of immunoglobulin supplementation in HGG related to lung transplantation over the long term or with recurrent infections is unknown.Trial RegistrationClinicaltrials.gov NCT00115778

The Economic and Clinical Implications of Antibiotic Resistance

T he E conomic and C linical I mplications of A ntibiotic R esistance Rohini Behl T T he P roblem The dilemma of antibiotic resistance has evolved to become a multifaceted issue exacerbated by a series of molecular, operational, psychological, and economic factors. On the molecular level, antibiotic resistance is the result of bacteria changing in ways that lead to the reduced effectiveness of antibiotics to cure or prevent infections. There are three main mechanisms through which resistance is acquired in bacteria: 1) Natural selection, or the gradual scientific process by which biological traits such as resistance to antibiotics become common in a population (i.e. bacteria); 2) plasmids, or independent circular pieces of DNA that may carry genes for antibiotic resistance that can be conferred between bacteria; and 3) mutations, or permanent changes in the DNA sequence of a gene that can lead to the formation of new traits such as resistance (Ramanan, 2012). Furthermore, cross- resistance, or the possession of a resistance mechanism by a bacterial strain that enables it to survive the effects of several antibacterial molecules, may continue even after halting or reducing antibiotic use. As such, antimicrobial resistant bacteria may emerge under the selective pressure of antibiotics and become the dominant flora. There are a series of operational factors, such as the role of setting, modes of transmission, and lack of regulation enforcement, that appear to be rather simple to remediate, but in practice this has not been the case. An increasing number of cases of antibiotic resistance occur within hospital and institutional settings; in these situations, antibiotic resistant flora may live within the institution and be transferred to the patient (Sipahi, 2008). Transmission may occur when coming into contact with soiled hands of staff as well as contaminated surfaces and equipment, in addition to passing from patient to patient, which is why effective infection control and hygiene are essential to inhibit their spread. The severity of the disease being treated, length of current hospital duration, exposure to other ill patients, invasive surgical procedures, intensity of clinical therapy, and advanced age further increase the odds of susceptibility to antibiotic resistant bacterial strains. Over-prescription of antibiotics by physicians further increases the likelihood that particular strains will develop resistance and can be simplified into two main causes: 1) consumer insistence that antibiotics are a magic cure-all for flu, infections, and unrecognizable conditions and 2) doctors’ fear of malpractice lawsuits that impels them to err on the side of over-prescription. For example, contracting the flu comes from a virus, rather than a particular bacterial strain; therefore there is no reason to take an antibiotic as treatment for the flu. Taking antibiotics more frequntly than necessary results in natural selection in the body for the most resistant bacteria and contributes to higher levels of resistance; consumers incorrectly believe “better safe than sorry” and thus err on the side of overconsumption of antibiotics when in reality, by doing so, they are increasing their odds of susceptibility to antibiotic resistant bacteria. For this reason, associations have provided and implemented regulations that restrict the supply of antibiotics created in the first place. However, these appear to be mainly ignored by antibiotic manufacturers in order to promote antibiotic sales and resulting profits. B erkeley S cientific J ournal • D eath and D ying • S pring 2013 • V olume 17 • I ssue 2 • 1 B S J here is no doubt that antibiotic resistance is a growing phenomenon. As Nobel Prize Winner and famed molecular biologist Joshua Lederberg put it, “We are running out of bullets for dealing with a number of bacterial infections. Patients are dying because we no longer in many cases have antibiotics that work (2007).” This issue can be attributed to over-prescription of available antibiotics, their currently limited diversity, as well as lack of incentives to encourage investment in development of new classes of antibiotics. Antibiotic resistance is a problem that afflicts both affluent and impoverished countries, and the outlook it generates appears to be bleak due to rapidly rising costs of treatment, the threat of cross-resistance, as well as increased morbidity.

Sitafloxacin

Sitafloxacin is a fluoroquinolone antibacterial with in vitro activity against a broad range of Gram-positive and -negative bacteria, including anaerobic bacteria, as well as against atypical pathogens. It is approved in Japan for use in a number of bacterial infections caused by sitafloxacin-susceptible strains of Staphylococcus spp., Streptococcus pneumoniae, other Streptococcus spp., Enterococcus spp., Moraxella catarrhalis, Escherichia coli, Citrobacter spp., Klebsiella spp., Enterobacter spp., Serratia spp., Proteus spp., Morganella morganii, Haemophilus influenzae, Pseudomonas aeruginosa, Legionella pneumophila, Peptostreptococcus spp., Prevotella spp., Porphyromonas spp., Fusobacterium spp., Chlamydia trachomatis, Chlamydophila pneumoniae and Mycoplasma pneumoniae. In terms of clinical efficacy, oral sitafloxacin was noninferior to oral levofloxacin in the treatment of community-acquired pneumonia or an infectious exacerbation of chronic respiratory tract disease, noninferior to oral tosufloxacin in the treatment of community-acquired pneumonia, and noninferior to oral levofloxacin in the treatment of complicated urinary tract infections, according to the results of randomized, double-blind, multicentre, noninferiority trials. Noncomparative studies demonstrated the efficacy of oral sitafloxacin in otorhinolaryngological infections, urethritis in men, C. trachomatis-associated cervicitis in women and odontogenic infections. Gastrointestinal disorders and laboratory abnormalities were the most commonly occurring adverse reactions in patients receiving oral sitafloxacin. Adverse reactions reported in sitafloxacin recipients in the active comparator trials were of mild to moderate severity.

Chronic bacterial and parasitic infections and cancer: a review

A relatively underestimated facet of infectious diseases is the association of chronic bacterial and parasitic infections with cancer development. Therefore, we sought to evaluate the evidence regarding the association of such infections with the development of malignancy, excluding the overwhelming evidence of the association of Helicobacter pylori and cancer. We searched Pubmed, Cochrane, and Scopus without time limits for relevant articles. There is evidence that some bacterial and parasitic infections are associated with cancer development. The level of evidence of this association varies from high to low; in any case, a long time interval is mandatory for the development of cancer. A high level of evidence exists for the association of Salmonella Typhi with gallbladder and hepatobiliary carcinoma; Opisthorchis viverrini and Clonorchis sinensis with cholangiocarcinoma; Schistosoma hematobium with bladder cancer; chronic osteomyelitis with squamous cell carcinoma of the skin; and hidradenitis suppurativa with squamous cell carcinoma of the skin. In contrast, the level of evidence regarding the association of Chlamydia spp. with cancer is low. Mycobacterium tuberculosis is associated with lung cancer, albeit probably not etiopathogenetically. A considerable number of bacterial infections and parasitic infections are associated with the development of cancer. Further research into recognizing additional associations of bacterial and parasitic infections with cancer is mandatory.

Intervention strategies for an influenza pandemic taking into account secondary bacterial infections

Influenza infections often predispose individuals to consecutive bacterial infections. Both during seasonal and pandemic influenza outbreaks, morbidity and mortality due to secondary bacterial infections can be substantial. With the help of a mathematical model, we investigate the potential impact of such bacterial infections during an influenza pandemic, and we analyze how antiviral and antibacterial treatment or prophylaxis affect morbidity and mortality. We consider different scenarios for the spread of bacteria, the emergence of antiviral resistance, and different levels of severity for influenza infections (1918-like and 2009-like). We find that while antibacterial intervention strategies are unlikely to play an important role in reducing the overall number of cases, such interventions can lead to a significant reduction in mortality and in the number of bacterial infections. Antibacterial interventions become even more important if one considers the–very likely–scenario that during a pandemic outbreak, influenza strains resistant to antivirals emerge. Overall, our study suggests that pandemic preparedness plans should consider intervention strategies based on antibacterial treatment or prophylaxis through drugs or vaccines as part of the overall control strategy. A major caveat for our results is the lack of data that would allow precise estimation of many of the model parameters. As our results show, this leads to very large uncertainty in model outcomes. As we discuss, precise assessment of the impact of antibacterial strategies during an influenza pandemic will require the collection of further data to better estimate key parameters, especially those related to the bacterial infections and the impact of antibacterial intervention strategies.