1.Application of central composite experimental design for the formulation and optimization of meropenem loaded chitosan-alginate nanoparticles
Clinton B. Gomez ; Jan Vonrich M. Huna ; Merrene Bright D. Judan ; Carl Edward F. Pahuyo
Philippine Journal of Health Research and Development 2024;28(1):32-36
Background:
Response surface methodology (RSM) is a cost-effective multivariate technique employed in optimization of pharmaceutical formulations. Central composite experiment design is one of the common designs under RSM used for determining optimum nanoparticle formulation parameters.
Objectives:
To optimize a formulation for meropenem-loaded chitosan alginate nanoparticles using central composite experimental design.
Methodology:
Meropenem loaded chitosan-alginate nanoparticles were fabricated using aqueous sodium alginate solution and ionotropic gelation with calcium chloride and chitosan, using an optimized formulation derived from a central composite design. The fabricated Mer-CS/Alg NPs were characterized for their particle size, zeta potential, encapsulation efficiency, and loading capacity. The central composite design has been used to adequately assess the influence of two factors namely meropenem concentration and Alg/CS mass ratio on the responses based on a limited number of 13 triplicate formulation runs.
Results:
This study successfully formulated meropenem-loaded chitosan/alginate nanoparticles. The optimal formulation of the Mer- CS/Alg NPs was 1.7 mg/mLcurcumin, and a Alg/CS mass ratio of 9.8:1. Based on the predicted values of the response variable, the optimal formulation would have a particle size of 490.64 nm, zeta potential of -28.59 mVand a loading capacity of 76.89%.
Conclusion
The central composite experimental design successfully optimized the nanoparticle formulation of meropenem and chitosan/alginate polymer solution. The optimum formulation produced nanoparticles with adequate size, high stability, and high drug load.
Meropenem
;
Nanoparticles
;
Research Design
2.The use of meropenem among neonates: A one-year retrospective study in the nursery of local tertiary hospital
Ferdinand P. Ganggangan ; Xenia Cathrine Fabay
Pediatric Infectious Disease Society of the Philippines Journal 2012;13(2):47-51
Objectives: This study was conducted to determine profile of neonates being treated with meropenem as well as to assess its clinical efficacy in the treatment of neonatal infections.
Methods: This is a retrospective review of the records of sick neonates admitted at the Newborn Care Unit of a tertiary hospital and treated with meropenem. Those discharged against advice were excluded. Frequency and percentage were used in comparing the following variables: sex, 5-minute APGAR score, age of gestation, birth weight, type of infection, culture results, treatment outcome, and adverse reactions.
Results: There were 34 charts available for review, but two were excluded. There were 62.5 % females and 37.5 % males: 28.1 % of them had a 5-minute APGAR score of 10; 37.5 % had 9; 21.9% had 8; and 12.5 % had 7. Sixty-two percent (62.5%) of the subjects were between 32 to 35 weeks age of gestation: 46.9 % were of low birth weight; 34.4 % were of very low birth weight; and 18.7 % had normal weights. Sepsis was the most common indication in the use of meropenem, followed by sepsis with pneumonia, pneumonia then sepsis with meningitis. Majority (68.75%) of the patients had no growth in their blood while 60% had no growth in the CSF. Enterobacter aerogenes (15.6%) was the most common blood isolate while Enterobacter gergeviae (20%) and Klebsiella pneumoniae (20%) were the isolates in the CSF culture. Treatment outcomes were favorable; 84.4% were improved, while 9.4% were unimproved and shifted to other antibiotics, and 6.2% died.
Conclusion: The use of meropenem is effective in the treatment of life-threatening infections among newborns.
Human
;
Male
;
Female
;
Infant Newborn
;
MEROPENEM
;
SEPSIS
;
INFECTIONS
3.Assessment of the ototoxic effects of amikacin and meropenem among neonates in a tertiary government hospital
Edgar Jake A. Agullo ; Francisco A. Victoria
Philippine Journal of Otolaryngology Head and Neck Surgery 2014;29(2):10-14
OBJECTIVE: Using pre- and post-treatment otoacoustic emission (OAE) tests, this study aimed to assess the ototoxic effect of meropenem, amikacin and meropenem plus amikacin among neonates treated for sepsis neonatorum in a neonatal intensive care unit versus untreated outpatient controls.METHODS: Design: Prospective Quasi-Experimental Controlled Clinical Trial Setting: Tertiary Government Hospital Subjects: Neonates treated for sepsis neonatorum in the Neonatal Intensive Care Unit between August to October 2012 who met inclusion criteria were included in this study. Controls were neonates born in the same institution who were not admitted and did not receive any antibiotic treatment. Excluded were those with APGAR < 5 at first minute, birth weight < 1000 grams, clinically evident congenital anomalies and initial "refer" results on OAE. Neonates were subjected to OAE testing before and after seven days treatment with amikacin, meropenem or a combination of both drugs. Results were analysed using chi-square test. Maternal drug intake, family history of hearing impairment and clinical outcomes (whether expired or discharged improved) were not included in this study. Assessment of ototoxic effects were limited to OAE alone and not confirmed by ABR.RESULTS: OAE "refer" rates were as follows: no amikacin and no meropenem, 0% (0/42); amikacin only, 33.3% (3/9); meropenem only, 25% (2/8) and amikacin and meropenem, 50% (10/20). Statistical analysis showed that hearing loss was dependent on treatment (c2 =23.741, p = < 0.001). Overall, statistical analysis showed that there is an increased risk of hearing loss when treated with amikacin and/or meropenem as compared to no treatment.CONCLUSION: There is an increased risk of ototoxicity when amikacin, meropenem or a combination of both drugs is administered to neonates. While the ototoxic effects of amikacin have been elucidated, further studies involving meropenem and its potential ototoxic effect are recommended.
Human
;
Male
;
Female
;
Infant Newborn
;
amikacin
;
meropenem
;
hearing loss
4.Clinical characteristics of patients with listeriosis.
Chaoxia WEI ; Pengcheng ZHOU ; Qianqian YE ; Xun HUANG ; Chunhui LI ; Anhua WU
Journal of Central South University(Medical Sciences) 2021;46(3):257-262
OBJECTIVES:
To investigate the clinical characteristics of patients with listeriosis and to provide a basis for diagnosis, treatment, prevention and control of hospital infection.
METHODS:
A total of 10 inpatients, who suffered from the listeriosis in Xiangya Hospital, Central South University from January 2013 to June 2019, were retrospectively collected for this study. The characteristics of the patients' age, gander, basic information, case type, clinical manifestations, first consultation department, days of diagnosis, infection indicator, specimen type, results of drug sensitivity, treatment plan, hospital infection or not, outcome, follow-up data were analyzed.
RESULTS:
Two cases were pregnant women and other were non-pregnant adults among 10 patients with listeriosis. Among them, there were 3 cases with hospital acquired infection. The age of patient onset was 27-71 years old, and the time from onset to diagnosis was 5-36 days. Five cases had fever, and other 5 cases had not fever. There were headache, fatigue, local pain, and other specialized symptoms in the 10 patients.The white blood cell count,the neutrophil ratio, the inflammatory index C-reactive protein, the procalcitonin were all increased, and the erythrocyte sedimentation was accelerated in the 10 patients.All the patients were sensitive to ampicillin, penicillin G, meropenem, and compound sinomine.
CONCLUSIONS
Listeriosis often affects the patients with low immunity, which often leads to misdiagnosis or missed diagnosis in clinic.So early prevention, early diagnosis, and early treatment can reduce mortality; it is important for departments of nosocomial infection management to manage patients' diet for avoiding outbreaks of listeriosis in hospital.
Adult
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Aged
;
Female
;
Humans
;
Listeria monocytogenes
;
Listeriosis/epidemiology*
;
Meropenem
;
Middle Aged
;
Pregnancy
;
Pregnancy Complications, Infectious
;
Retrospective Studies
5.Clinical Analysis of Colistin Sulfate in the Treatment of Hematonosis Infected by Multidrug-Resistant Gram-Negative Bacteria.
Yuan-Bing WU ; Shan-Shan JIANG ; Ya-Xue WU ; Dong-Yang LI ; Qian LI ; Xing WANG ; Bin LIU ; Hai-Yan BAO ; Xiao-Hui HU
Journal of Experimental Hematology 2023;31(6):1878-1884
OBJECTIVE:
To investigate the efficacy and safety of colistin sulfate in the treatment of hematonosis patients infected by multidrug-resistant (MDR) gram-negative bacteria (GNB), and discuss the possible factors that affect the efficacy of colistin sulfate.
METHODS:
The clinical data of 85 hematologic patients infected with MDR GNB in the Soochow Hopes Hematonosis Hospital from April 2022 to November 2022 were collected and divided into clinically effective group with 71 cases and ineffective group with 14 cases according to the therapeutic efficacy of colistin sulfate. The age, gender, type of hematologic disease, status of hematopoietic stem cell transplantation, infection sites, type of pathogen, timing of administration, daily dose and duration of colistin sulfate, and combination with other antibacterial agents of patients in two groups were compared. Logistic regression was used to analyze on the meaningful variables to study the influencing factors of colistin sulfate. The adverse reactions of colistin sulfate were also evaluated.
RESULTS:
There were no significant differences in age, gender, type of hematologic disease, hematopoietic stem cell transplantation status, infection sites and pathogen type between the effective group and the ineffective group (P>0.05). Compared with the medication time more than 7 days, meropenem used within 7 days in the clinical effective group, and timely replacement with colistin sulfate could obtain better efficacy, the difference was statistically significant (P=0.018). The duration of tigacycline before colistin sulfate did not affect the efficacy, and there was no significant difference in efficacy between the effective and ineffective groups. The therapeutic effect of colistin sulfate at daily dose of 500 000 U q8h was better than that of 500 000 U q12h, the difference was statistically significant (P=0.035). The time of colistin sulfate use in the clinically effective group was longer than that in the ineffective group, which had a statistical difference (P=0.003). Compared with the clinical ineffective group, the efficacy of combination regimens with colistin sulfate was better than that of colistin sulfate monotherapy, and the difference was statistically significant (P=0.013). Multivariate logistic regression analysis was performed on the indicators with statistical differences in the two groups of patients, which suggested that the use time of colistin sulfate (B: 2.358; OR: 10.573; CI: 1.567-71.361; P=0.015) and the combination of colistin sulfate (B: 1.720; OR: 5.586; CI: 1.210-25.787; P=0.028) were influential factors in the efficacy of colistin sulfate. During the treatment, the incidence of nephrotoxicity, hepatotoxicity and peripheral neurotoxicity were 5.9%, 1.2% and 1.2%, respectively.
CONCLUSION
The use of colistin sulfate improves the clinical efficacy of MDR GNB infections in hematological patients, and the timing of colistin sulfate administration and the combination of drugs are independent factors affecting its clinical efficacy, and the safety during treatment is high.
Humans
;
Colistin/adverse effects*
;
Anti-Bacterial Agents/therapeutic use*
;
Meropenem/adverse effects*
;
Treatment Outcome
;
Gram-Negative Bacteria
;
Hematologic Diseases
6.Prevalence of healthcare-associated infections among the pediatric patients admitted at Philippine General Hospital from the years 2011-2014.
Edilberto B. Garcia ; Sarah R. Makalinaw ; Lourdes Bernadeth V. Manipon
Pediatric Infectious Disease Society of the Philippines Journal 2015;16(1):12-20
INTRODUCTION: Healthcare associated infections (HAIs) continue to be a major public health concern throughout the world particularly in developing countries wherein prevalence rates range from 5.7%-19.1%.
OBJECTIVES: The aims of this study were to determine the prevalence of HAIs among pediatric patients admitted at Philippine General Hospital and to describe the trends of annual prevalence of HAIs in relation to infection control programs implemented.
METHODOLOGY: A retrospective study was conducted at the 145-bed capacity wards and intensive care units of the Department of Pediatrics, Philippine General Hospital (PGH) from January 2011 to December 2014 wherein HAI records from the database of the Section of Infectious and Tropical Disease in Pediatrics (INTROP) were reviewed. The following data were collected and encoded: (1) number of patients admitted in the different areas: Pediatric wards (Ward 9 and Ward 11), PICU and NICU; (2) number of patients who developed HAIs; and (3) microbial isolates, sites and antibiotic susceptibility results. Trends of yearly prevalence of HAIs in relation to infection programs implemented were determined, and the microbial isolates and their antibiotic sensitivity patterns were described.
RESULTS: Among 30,032 pediatric patients at risk for HAIs and admitted from January 2011 to December 2014, the prevalence of HAI was 11.37%. There was a decreasing trend in the yearly HAI rates from 2011 to 2014 which coincided with implementation of infection control programs and hiring of a part-time infection control nurse in 2012. The prevalence of HAIs was highest at the PICU (15.17%- 27.81%) followed by the two Pediatric wards, ward 9 (9.03%-19.87%) and ward 11(8.75%-14.76%) and lowest at the NICU (7.52%-9.44%). Top isolates were Pseudomonas putida, Pseudomonas aeruginosa, and Klebsiella pneumonia. Pseudomonas organisms were still sensitive to Ceftazidime, and Klebsiella to Meropenem.
CONCLUSION: The overall HAI prevalence during the 4-year study period was 11.37% (9.14% - 13.65%) comparable to those seen in developing countries. There was a decreasing trend of prevalence annually that coincided with the implementation of various infection control programs and the hiring of a part-time infection control nurse. The microbial isolates obtained vary per area but overall the same organisms were isolated during the study periods which were susceptible to the empiric treatment given.
Human ; Male ; Female ; Cross Infection ; Ceftazidime ; Pseudomonas Aeruginosa ; Meropenem ; Anti-bacterial Agents ; Pseudomonas Putida ; Klebsiella ; Intensive Care Units, Neonatal ; Infection Control ; Thienamycins
7.Study on drug sensitivity against Comamonas testosteroni by Kirby-Bauer disk diffusion method.
Changsheng KONG ; Jun CHEN ; Xiaoyan ZOU ; Yi ZHANG ; Lingna ZHU
Journal of Central South University(Medical Sciences) 2016;41(8):856-859
OBJECTIVE:
To determine the drug resistance of Comamonas testosteroni (C. testosteroni) by the Kirby-Bauer (K-B) method without Clinical and Laboratory Standards Institute (CLSI) explanation or the minimum inhibitory concentration (MIC) method with the standard CLSI explanation to evaluate the sensitivity of K-B method in detection of C. testosteroni.
METHODS:
K-B method and MIC method was used to determine the sensitivity of C. testosteroni to Piperacillin, Cefepime, Piperacillin/tazobactam, Imipenem, Meropenem, Amikacin, Gentamicin, Tobramycin, Ceftazidime and Ciprofloxacin. The interpretation standard for Pseudomonas aeruginosa was temporary used for the K-B method. The coincident rate was compared between the two methods.
RESULTS:
The complete or partial coincident rate for K-B method and MIC method to detect Piperacillin and Cefepime was 97.4% or 2.6%; the complete coincidence rate to detect Piperacillin/tazobactam, Imipenem and Meropenem was 100%; the complete or partial coincident rate to detect Amikacin, Gentamicin and Tobramycin 94.7% or 5.3%; the complete or partial coincident rate to detect Ceftazidime was 97.4% or 2.6%; the complete or partial coincident rate to detect Ciprofloxacin 86.8% or 10.6%, and the full non-coincidence rate was 2.6%.
CONCLUSION
The results of drug sensitive test from the two methods are highly consistent. We suggest that the microbiology labs do not report the interpretive results for C. testosteroni with K-B method but report the test results.
Anti-Bacterial Agents
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Cefepime
;
Cephalosporins
;
Comamonas testosteroni
;
Imipenem
;
Meropenem
;
Microbial Sensitivity Tests
;
Penicillanic Acid
;
analogs & derivatives
;
Piperacillin
;
Piperacillin, Tazobactam Drug Combination
;
Pseudomonas aeruginosa
;
Thienamycins
8.Surveillance of bacterial resistance in children aged 0-14 years from 2018 to 2022.
Chinese Journal of Pediatrics 2023;61(11):1001-1010
Objective: To understand the distribution and antimicrobial resistance of common bacteria from children aged 0-14 years from China Antimicrobial Resistance Surveillance System. Methods: Bacterial resistance data of 2 575 040 strains from children aged 0-14 years were extracted from the national bacterial resistance surveillance reports from October 2018 to September 2022 and resistance changes were further analyzed by comparing with all data in each year. Results: The total number of bacteria isolated from children in 2018-2022 ranged from 415 306-588 016 strains, accounted for 15.9% (514 193/3 234 372), 16.2% (572 107/3 528 471), 12.8% (415 306/3 249 123), 13.0% (485 418/3 743 027), and 12.2% (588 016/4 828 509), respectively. The proportions of gram-positive bacteria among children were 45.4% (233 456/514 193), 44.5% (254 869/572 107), 44.7% (185 756/415 306), 42.6% (206 903/485 418), and 41.7% (245 044/588 016), respectively. The top five isolates of gram-positive bacteria were Staphylococcus aureus (36.0%-38.8%), Streptococcus pneumoniae (27.1%-31.7%), Staphylococcus epidermidis (7.3%-9.3%), Enterococcus faecium (4.0%-4.8%), and Enterococcus faecium (2.5%-3.6%), and the top five isolates of gram-negative bacteria were Escherichia coli (21.8%-26.2%), Haemophilus influenzae (14.4%-26.4%), Klebsiella pneumoniae (10.1%-14.7%), Moraxella catarrhalis (7.3%-11.9%), and Pseudomonas aeruginosa (5.5%-6.8%). The bacteria from children aged 0-14 years commonly isolated from sputum samples (48.8%-57.0%). The prevalence of methicillin-resistant S. aureus was 28.7%-30.1%. The detection rates of vancomycin-resistant E. faecalis or E. faecium were 0.1%-0.3%. The proportions of non-cerebrospinal fluid-derived penicillin-resistant S. pneumoniae were 0.7%-1.6%. The prevalence of cefotaxime and (or) ceftriaxone-resistant E. coli and K. pneumoniae decreased were 43.7%-50.0% and 31.8%-42.7%, respectively. The resistant rates of E. coli to imipenem and meropenem were 1.2%-1.9% and 1.2%-2.0%, respectively, and the resistant rates of K. pneumoniae to imipenem and meropenem were 7.3%-10.1% and 8.2%-12.2%, respectively. About 6.6%-10.2% and 5.3%-9.6% of the P. aeruginosa isolates showed resistant to imipenem and meropenem, respectively, while 17.2%-24.0% and 19.0%-29.4% of the Acinetobacter baumannii isolates were resistant to imipenem and meropenem, respectively. Conclusions: There is no significant change in the composition of common clinical pathogens in children aged 0-14 years from 2018 to 2022. The prevalence of some resistant bacteria such as methicillin-resistant S. aureus and carbapenem-resistant Enterobacterales is decreasing. However, it is necessary to pay attention to antimicrobial resistance of bacteria from children and long-term monitoring of the prevalence of resistant bacteria should be conducted.
Child
;
Humans
;
Anti-Bacterial Agents/therapeutic use*
;
Meropenem
;
Methicillin-Resistant Staphylococcus aureus
;
Escherichia coli
;
Microbial Sensitivity Tests
;
Bacteria
;
Gram-Positive Bacteria
;
Staphylococcal Infections/drug therapy*
;
Klebsiella pneumoniae
;
Imipenem
;
Drug Resistance, Bacterial