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1.
J Trop Pediatr ; 68(4)2022 06 06.
Article in English | MEDLINE | ID: covidwho-1878823

ABSTRACT

Fever without a source (FWS) is common clinical status in the young infants. The aim of this study was to evaluate the clinical and laboratory findings of coronavirus disease (COVID-19) infection in well-appearing infants with FWS. Well-appearing febrile infants between 30 and 90 days who were evaluated as FWS in the pediatric emergency department and tested for COVID-19 were divided into two groups: COVID-19 (+) and (-). The clinical and laboratory findings of the patients were compared. The study included 95 febrile infants with FWS, and the mean age was 59.62 ± 16.82 days. The nasopharyngeal COVID-19 polymerase chain reaction test results of 29/95 (30.5%) patients were positive, while 66/95 (69.5%) were negative. The complaints of irritability and nasal congestion were found to be significantly more common in COVID-19-positive patients (p = 0.04 and p = 0.041, respectively). The hospitalization rate (p = 0.009), length of hospital stay (p = 0.026), initiation of antibiotic treatment (p < 0.001) and duration of antibiotic treatment (p = 0.036) were significantly lower in the COVID-19 (+) patients. The C-reactive protein (CRP, p < 0.001), absolute neutrophil count (ANC, p < 0.001), absolute lymphocyte count (ALC, p = 0.015), white blood cell (WBC, p < 0.001) and systemic immune-inflammation index (SII, p < 0.001) were found to be significantly lower in the COVID-19 (+) patient group. There was no significant difference between the groups in terms of neutropenia, lymphopenia or leukopenia.COVID-19 infection may present as an FWS. During the pandemic period, testing for COVID-19 among infants who were evaluated as FWS may reduce unnecessary hospitalizations and antibiotic treatments, and shorten hospital stays and duration of antibiotics.


Subject(s)
COVID-19 , Adult , Aged , Anti-Bacterial Agents/therapeutic use , C-Reactive Protein/analysis , COVID-19/diagnosis , COVID-19 Testing , Child , Fever/drug therapy , Fever/etiology , Humans , Infant , Leukocyte Count , Middle Aged
2.
J Antibiot (Tokyo) ; 75(6): 321-332, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1878523

ABSTRACT

Staphylococcus aureus is one of the most dangerous pathogens commonly associated with high levels of morbidity and mortality. Sortase A is considered as a promising molecular target for the development of antistaphylococcal agents. Using hybrid virtual screening approach and FRET analysis, we have identified five compounds able to decrease the activity of sortase A by more than 50% at the concentration of 200 µM. The most promising compound was 2-(2-amino-3-chloro-benzoylamino)-benzoic acid which was able to inhibit S. aureus sortase A at the IC50 value of 59.7 µM. This compound was selective toward sortase A compared to other four cysteine proteases - cathepsin L, cathepsin B, rhodesain, and the SARS-CoV2 main protease. Microscale thermophoresis experiments confirmed that this compound bound sortase A with KD value of 189 µM. Antibacterial and antibiofilm assays also confirmed high specificity of the hit compound against two standard and three wild-type, S. aureus hospital infection isolates. The effect of the compound on biofilms produced by two S. aureus ATCC strains was also observed suggesting that the compound reduced biofilm formation by changing the biofilm structure and thickness.


Subject(s)
COVID-19 , Staphylococcal Infections , Aminoacyltransferases , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/metabolism , Biofilms , Cysteine Endopeptidases , Humans , Microbial Sensitivity Tests , RNA, Viral/pharmacology , SARS-CoV-2 , Staphylococcus aureus
3.
J Clin Lab Anal ; 36(6): e24427, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1877605

ABSTRACT

BACKGROUND: Azithromycin (AZM), sold under the name Zithromax, is classified as a macrolide. It has many benefits due to its immunomodulatory, anti-inflammatory, and antibacterial effects. This review aims to study different clinical and biochemisterial aspects and properties of this drug which has a priority based on literature published worldwide. METHODS: Several databases including Web of Science, Google Scholar, PubMed, and Scopus were searched to obtain the relevant studies. RESULTS: AZM mechanism of action including the inhibition of bacterial protein synthesis, inhibition of proinflammatory cytokine production, inhibition of neutrophil infestation, and macrophage polarization alteration, gives it the ability to act against a wide range of microorganisms. Resistant organisms are spreading and being developed because of the irrational use of the drug in the case of dose and duration. AZM shows synergistic effects with other drugs against a variety of organisms. This macrolide is considered a valuable antimicrobial agent because of its use as a treatment for a vast range of diseases such as asthma, bronchiolitis, COPD, cystic fibrosis, enteric infections, STIs, and periodontal infections. CONCLUSIONS: Our study shows an increasing global prevalence of AZM resistance. Thus, synergistic combinations are recommended to treat different pathogens. Moreover, continuous monitoring of AZM resistance by registry centers and the development of more rapid diagnostic assays are urgently needed.


Subject(s)
Azithromycin , Cystic Fibrosis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Azithromycin/pharmacology , Azithromycin/therapeutic use , Bacterial Proteins , Cystic Fibrosis/drug therapy , Cystic Fibrosis/microbiology , Humans
4.
Huan Jing Ke Xue ; 43(6): 2996-3004, 2022 Jun 08.
Article in Chinese | MEDLINE | ID: covidwho-1876194

ABSTRACT

The seasonal variation and spatial distribution of pharmaceuticals in typical drinking water sources in the middle reaches of the Yangtze River were analyzed using the solid-phase extraction and high-performance liquid chromatography-tandem mass spectrometry methods. Combined with the risk entropy method, the corresponding ecological risks for aquatic organisms were evaluated. The results showed that 80% of the target pharmaceuticals were detected in the drinking water sources, with average concentrations of 0.07-13.00 ng·L-1. The concentrations of the target pharmaceuticals were lower than or comparable with those in other drinking water sources reported in China. The spatiotemporal distribution of different pharmaceuticals varied. Generally, the detection level in winter was higher than that in summer, and there was no significant difference between that upstream and that downstream. This might be mainly attributed to seasonal/regional use and emissions of the pharmaceuticals, the impact of flow rate on dilution, and the impact of temperature on biodegradation. Compared with those before the COVID-19 epidemic, the detection concentrations of the target pharmaceuticals were relatively low. The reason for this might be that the prevention and control of the epidemic reduced the use and emission of the pharmaceuticals to a certain extent, and the high rainfall and runoff strengthened the dilution of water flow. The target pharmaceuticals, especially antibiotics, posed medium or low risks to aquatic organisms (especially algae). Considering the ecological risks and genotoxicity of pharmaceuticals and the potential risks of antibiotic-resistant genes, it is suggested to strengthen the investigation, evaluation, treatment, and control of pharmaceuticals in the water environment.


Subject(s)
COVID-19 , Drinking Water , Water Pollutants, Chemical , Anti-Bacterial Agents/analysis , Aquatic Organisms , China , Drinking Water/analysis , Environmental Monitoring/methods , Humans , Pharmaceutical Preparations , Risk Assessment , Water Pollutants, Chemical/analysis
5.
Molecules ; 27(10)2022 May 16.
Article in English | MEDLINE | ID: covidwho-1875714

ABSTRACT

Natural origin molecules represent reliable and excellent sources to overcome some medicinal problems. The study of anticancer, anticoagulant, and antimicrobial activities of Thevetia peruviana latex were the aim of the current research. An investigation using high-performance liquid chromatography (HPLC) revealed that the major content of the flavonoids are rutin (11.45 µg/mL), quersestin (7.15 µg/mL), naringin (5.25 µg/mL), and hisperdin (6.07 µg/mL), while phenolic had chlorogenic (12.39 µg/mL), syringenic (7.45 µg/mL), and ferulic (5.07 µg/mL) acids in latex of T. peruviana. Via 1,1-diphenyl-2- picrylhydrazyl (DPPH) radical scavenging, the experiment demonstrated that latex had a potent antioxidant activity with the IC50 43.9 µg/mL for scavenging DPPH. Hemolysis inhibition was 58.5% at 1000 µg/mL of latex compared with 91.0% at 200 µg/mL of indomethacin as positive control. Negligible anticoagulant properties of latex were reported where the recorded time was 11.9 s of prothrombin time (PT) and 29.2 s of the activated partial thromboplastin time (APTT) at 25 µg/mL, compared with the same concentration of heparin (PT 94.6 s and APPT 117.7 s). The anticancer potential of latex was recorded against PC-3 (97.11% toxicity) and MCF-7 (96.23% toxicity) at 1000 µg/mL with IC50 48.26 µg/mL and 40.31 µg/mL, respectively. Disc diffusion assessment for antimicrobial activity recorded that the most sensitive tested microorganisms to latex were Bacillus subtilis followed by Escherichia coli, with an inhibition zone (IZ) of 31 mm with minimum inhibitory concentration (MIC) (10.2 µg/mL) and 30 mm (MIC, 12.51 µg/mL), respectively. Moreover, Candida albicans was sensitive (IZ, 28 mm) to latex, unlike black fungus (Mucor circinelloides). TEM examination exhibited ultrastructure changes in cell walls and cell membranes of Staphylococcus aureus and Pseudomonas aeruginosa treated with latex. Energy scores of the molecular docking of chlorogenic acid with E. coli DNA (7C7N), and Rutin with human prostate-specific antigen (3QUM) and breast cancer-associated protein (1JNX), result in excellent harmony with the experimental results. The outcome of research recommended that the latex is rich in constituents and considered a promising source that contributes to fighting cancer and pathogenic microorganisms.


Subject(s)
Anti-Infective Agents , Thevetia , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Anticoagulants/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Escherichia coli , Humans , Latex , Molecular Docking Simulation , Rutin
6.
Int J Environ Res Public Health ; 19(8)2022 04 15.
Article in English | MEDLINE | ID: covidwho-1875582

ABSTRACT

There are no previous studies reporting the type and quantity of pesticides for farming from Sierra Leone and the impact of Ebola or COVID-19 on importation. This study reviewed imported farming pesticides by the Sierra Leone, Ministry of Agriculture and Forestry (MAF), between 2010-2021. It was a descriptive study using routinely collected importation data. We found the MAF imported pesticides for farming only during 2010, 2014 and 2021, in response to growing food insecurity and associated with Ebola and COVID-19 outbreaks. Results showed insecticide importation increased from 6230 L in 2010 to 51,150 L in 2021, and importation of antimicrobial pesticides (including fungicides) increased from 150 kg in 2010 to 23,560 kg in 2021. The hazard class risk classification of imported pesticides decreased over time. Increasing amounts of imported fungicides could increase the risk of future fungal resistance among humans. We found that in responding to escalating food insecurity, the government dramatically increased the amount of pesticide importation to improve crop production. Further support is necessary to decrease the risk of worsening food shortages and the possible threat of emerging antimicrobial resistance. We recommend continued monitoring and surveillance, with further studies on the most appropriate response to these multiple challenges.


Subject(s)
COVID-19 , Fungicides, Industrial , Hemorrhagic Fever, Ebola , Pesticides , Anti-Bacterial Agents , Disease Outbreaks , Drug Resistance, Bacterial , Hemorrhagic Fever, Ebola/epidemiology , Humans , Sierra Leone/epidemiology
7.
Antimicrob Agents Chemother ; 66(6): e0025422, 2022 Jun 21.
Article in English | MEDLINE | ID: covidwho-1874495

ABSTRACT

The objective of this study was to describe the population pharmacokinetics of remdesivir and GS-441524 in hospitalized coronavirus disease 2019 (COVID-19) patients. A prospective observational pharmacokinetic study was performed in non-critically ill hospitalized COVID-19 patients with hypoxemia. For evaluation of the plasma concentrations of remdesivir and its metabolite GS-441524, samples were collected on the first day of therapy. A nonlinear mixed-effects model was developed to describe the pharmacokinetics and identify potential covariates that explain variability. Alternative dosing regimens were evaluated using Monte Carlo simulations. Seventeen patients were included. Remdesivir and GS-441524 pharmacokinetics were best described by a one-compartment model. The estimated glomerular filtration rate (eGFR) on GS-441524 clearance was identified as a clinically relevant covariate. The interindividual variability in clearance and volume of distribution for both remdesivir and GS-441524 was high (remdesivir, 38.9% and 47.9%, respectively; GS-441525, 47.4% and 42.9%, respectively). The estimated elimination half-life for remdesivir was 0.48 h, and that for GS-441524 was 26.6 h. The probability of target attainment (PTA) of the in vitro 50% effective concentration (EC50) for GS-441524 in plasma can be improved by shortening the dose interval of remdesivir and thereby increasing the total daily dose (PTA, 51.4% versus 94.7%). In patients with reduced renal function, the metabolite GS-441524 accumulates. A population pharmacokinetic model for remdesivir and GS-441524 in COVID-19 patients was developed. Remdesivir showed highly variable pharmacokinetics. The elimination half-life of remdesivir in COVID-19 patients is short, and the clearance of GS-441524 is dependent on the eGFR. Alternative dosing regimens aimed at optimizing the remdesivir and GS-441524 concentrations may improve the effectiveness of remdesivir treatment in COVID-19 patients.


Subject(s)
COVID-19 , Adenosine/analogs & derivatives , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Anti-Bacterial Agents/pharmacokinetics , COVID-19/drug therapy , Critical Illness/therapy , Furans , Humans , Monte Carlo Method , Triazines
8.
Sci Rep ; 12(1): 8763, 2022 May 24.
Article in English | MEDLINE | ID: covidwho-1873545

ABSTRACT

Cefiderocol (CFDC) is a novel chlorocatechol-substituted siderophore antibiotic approved to treat complicated urinary tract infections (cUTI) and hospital-acquired and ventilator-acquired pneumonia (HAP/VAP). Previous work determined that albumin-rich human fluids increase the minimum inhibitory concentration (MICs) of Acinetobacter baumannii against CFDC and reduce the expression of genes related to iron uptake systems. This latter effect may contribute to the need for higher concentrations of CFDC to inhibit growth. The presence of human urine (HU), which contains low albumin concentrations, did not modify MIC values of two carbapenem-resistant A. baumannii. Levels of resistance to CFDC were not modified by HU in strain AMA40 but were reduced in strain AB5075. Expanding the studies to other carbapenem-resistant A. baumannii isolates showed that the presence of HU resulted in unmodified or reduced MIC of CDFC values. The expression of piuA, pirA, bauA, and bfnH determined by qRT-PCR was enhanced in A. baumannii AMA40 and AB5075 by the presence of HU in the culture medium. All four tested genes code for functions related to recognition and transport of ferric-siderophore complexes. The effect of HU on expression of pbp1, pbp3, blaOXA-51-like, blaADC, and blaNDM-1, genes associated with resistance to ß-lactams, as well as genes coding for efflux pumps and porins was variable, showing dependence with the strain analyzed. We conclude that the lack of significant concentrations of albumin and free iron in HU makes this fluid behave differently from others we tested. Unlike other albumin rich fluids, the presence of HU does not impact the antibacterial activity of CFDC when tested against A. baumannii.


Subject(s)
Acinetobacter baumannii , Albumins/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Carbapenems/pharmacology , Cephalosporins , Humans , Iron/pharmacology , Microbial Sensitivity Tests , Siderophores , beta-Lactamases/genetics
9.
BMC Prim Care ; 23(1): 135, 2022 May 31.
Article in English | MEDLINE | ID: covidwho-1869063

ABSTRACT

BACKGROUND: Social distancing and lockdowns were implemented during the first period of the COVID-19 pandemic. Primary care physicians needed to adapt quickly to deliver remote care/telemedicine. METHODS: A cross-sectional, 47-item online Google Survey was distributed through the Israel Association of Family Physicians (IAFP) mailing list between March 31-May 5, 2020. The questionnaire included demographics, physician characteristics, and information on usage and perceived telemedicine quality. Sampling weights by sex and age groups were applied. RESULTS: One hundred fifty-nine primary care physicians (10.6% of registered IAFP members; 63.5% women; mean age 53.4 ± 10.4 years and median professional experience 21.3 years) replied to the survey. The majority (59.7%) of the participants performed a mixture of in-person along with phone counseling. About 40% had no former telemedicine experience. The majority indicated that telephone and video formats were inferior to in-person consultation (68%, 57.1% online and phone, respectively). The overall counseling quality grade (on a 1-10 scale,)median (IQR)) was 6.2 (3) for telephone and 7(2) for video. While 66.9% reported experiencing no challenges, 10% had technical problems, 10% interpersonal problems, 5.6% scheduling difficulties, and 7.5% other difficulties. Majority of 56.6% physicians indicated they prescribed more antibiotics,16.4% sent more blood tests, 24.5% referred more to experts, and 49.7% referred more to imaging in comparison to usual counseling. Higher phone quality score was significantly associated with physicians who indicated not prescribing more antibiotics during the pandemic (OR = 0.30, 95%CI 0.134-0.688, p = 0.004). Higher online quality score was associated with physicians who indicated not sending more blood tests during the pandemic (OR = 0.06 95%CI 0.008-0.378, P = 0.003). CONCLUSIONS: Our findings suggest telehealth holds considerable promise for counseling in the primary care setting. However, interpersonal challenges raised by physicians should be understood in-depth to develop tailored training and further examine it in randomized trials while integrating patient-reported outcomes. Finally, further research on utility, cost, and cost-efficiency during remote counseling with follow-ups, medical prescribing, and additional referrals is needed.


Subject(s)
COVID-19 , Pandemics , Adult , Anti-Bacterial Agents , COVID-19/epidemiology , Communicable Disease Control , Cross-Sectional Studies , Disease Outbreaks , Female , Humans , Male , Middle Aged , Pandemics/prevention & control , Physicians, Family , Primary Health Care
11.
Balkan Med J ; 39(3): 209-217, 2022 05 24.
Article in English | MEDLINE | ID: covidwho-1865616

ABSTRACT

Background: Broad-spectrum empirical antimicrobials are frequently prescribed for patients with coronavirus disease 2019 (COVID-19) despite the lack of evidence for bacterial coinfection. Aims: We aimed to cross-sectionally determine the frequency of antibiotics use, type of antibiotics prescribed, and the factors influencing antibiotics use in hospitalized patients with COVID-19 confirmed by polymerase chain reaction. Study Design: The study was a national, multicenter, retrospective, and single-day point prevalence study. Methods: This was a national, multicenter, retrospective, and single-day point-prevalence study, conducted in the 24-h period between 00:00 and 24:00 on November 18, 2020, during the start of the second COVID-19 peak in Turkey. Results: A total of 1500 patients hospitalized with a diagnosis of COVID-19 were included in the study. The mean age ± standard deviation of the patients was 65.0 ± 15.5, and 56.2% (n = 843) of these patients were men. Of these hospitalized patients, 11.9% (n = 178) were undergoing invasive mechanical ventilation or ECMO. It was observed that 1118 (74.5%) patients were receiving antibiotics, of which 416 (37.2%) were prescribed a combination of antibiotics. In total, 71.2% of the patients had neither a clinical diagnosis nor microbiological evidence for prescribing antibiotics. In the multivariate logistic regression analysis, hospitalization in a state hospital (p < 0.001), requiring any supplemental oxygen (p = 0.005), presence of moderate/diffuse lung involvement (p < 0.001), C-reactive protein > 10 ULT coefficient (p < 0.001), lymphocyte count < 800 (p = 0.007), and clinical diagnosis and/or confirmation by culture (p < 0.001) were found to be independent factors associated with increased antibiotic use. Conclusion: The necessity of empirical antibiotics use in patients with COVID-19 should be reconsidered according to their clinical, imaging, and laboratory findings.


Subject(s)
Anti-Bacterial Agents , COVID-19 , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , COVID-19/drug therapy , Cross-Sectional Studies , Female , Hospitalization , Humans , Male , Middle Aged , Prevalence , Retrospective Studies , SARS-CoV-2 , Turkey/epidemiology
12.
Front Cell Infect Microbiol ; 12: 866186, 2022.
Article in English | MEDLINE | ID: covidwho-1865449

ABSTRACT

Streptococcus pneumoniae upper respiratory infections and pneumonia are often treated with macrolides, but recently macrolide resistance is becoming an increasingly important problem. The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the National Immunization Program of Peru in 2015. This study aimed to evaluate the temporal evolution of macrolide resistance in S. pneumoniae isolates collected in five cross-sectional studies conducted before and after this vaccine introduction, from 2006 to 2019 in Lima, Peru. A total of 521 and 242 S. pneumoniae isolates recovered from nasopharyngeal swabs from healthy carrier children < 2 years old (2 carriage studies) and samples from normally sterile body areas from pediatric patients with invasive pneumococcal disease (IPD) (3 IPD studies), respectively, were included in this study. Phenotypic macrolide resistance was detected using the Kirby-Bauer method and/or MIC test. We found a significant increase in macrolide resistance over time, from 33.5% to 50.0% in carriage studies, and from 24.8% to 37.5% and 70.8% in IPD studies. Macrolide resistance genes [erm(B) and mef(A/E)] were screened using PCR. In carriage studies, we detected a significant decrease in the frequency of mef(A/E) genes among macrolide-resistant S. pneumoniae strains (from 66.7% to 50.0%) after introduction of PCV13. The most common mechanism of macrolide-resistant among IPD strains was the presence of erm(B) (96.0%, 95.2% and 85.1% in the 3 IPD studies respectively). Macrolide resistance was more common in serotype 19A strains (80% and 90% among carriage and IPD strains, respectively) vs. non-serotype 19A (35.5% and 34.4% among carriage and IPD strains, respectively). In conclusion, S. pneumoniae macrolide resistance rates are very high among Peruvian children. Future studies are needed in order to evaluate macrolide resistance trends among pneumococcal strains, especially now after the COVID-19 pandemic, since azithromycin was vastly used as empiric treatment of COVID-19 in Peru.


Subject(s)
COVID-19 , Pneumococcal Infections , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Child , Child, Preschool , Cross-Sectional Studies , Drug Resistance, Bacterial , Humans , Infant , Macrolides/pharmacology , Pandemics , Peru/epidemiology , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines , Serogroup , Streptococcus pneumoniae , Vaccines, Conjugate
13.
Microb Drug Resist ; 28(5): 601-610, 2022 May.
Article in English | MEDLINE | ID: covidwho-1864944

ABSTRACT

This retrospective study aims to describe the etiology and resistance patterns of pathogens causing bacteremia in children with solid tumors in a tertiary pediatric hematology-oncology center in Jerusalem, Israel (2011-2019). Factors associated with multidrug-resistant (MDR) bacteremia and mortality were analyzed. A total of 228 pathogens were isolated in 126 patients; 61.0% were gram-negative rods (GNR) and 38.2% were gram-positive cocci (GPC). The most common pathogens were Klebsiella pneumoniae (19.3%), Escherichia coli (17.5%), and coagulase-negative staphylococci (16.2%). The proportion of MDR-GNR was 18.2%, while the proportion of MDR-GPC was 55.2%. In logistic regression analysis, breakthrough bacteremia on a penicillin-group antibiotic (odds ratio [OR] 5.69, [95% confidence interval 1.42-22.76], p-value = 0.014) was associated and underlying diagnosis of neuroblastoma was inversely associated (OR 0.17, [0.04-0.81], p-value = 0.026) with MDR-GNR bacteremia; while the previous hospitalizations' duration (OR 1.032/day, [1.01-1.06], p-value = 0.007) and oncologic treatment intensity (OR 2.19, [1.08-4.45, p-value = 0.03) were associated with MDR-GPC bacteremia. Shock, prolonged profound neutropenia, and pediatric intensive care unit (PICU) admission were associated with 7-day mortality; and relapsed disease, oncologic treatment intensity, prolonged profound neutropenia, and PICU admission-with 30-day mortality in the univariate analyses. Empirical antibiotic choice should be based on factors associated with MDR infections in this specific population.


Subject(s)
Bacteremia , Gram-Negative Bacterial Infections , Neoplasms , Neutropenia , Anti-Bacterial Agents/pharmacology , Bacteremia/drug therapy , Bacteremia/epidemiology , Child , Drug Resistance, Multiple , Escherichia coli , Gram-Negative Bacteria , Gram-Negative Bacterial Infections/drug therapy , Humans , Neoplasms/complications , Neoplasms/drug therapy , Neoplasms/pathology , Neutropenia/complications , Neutropenia/drug therapy , Retrospective Studies
15.
JAMA Pediatr ; 176(3): 253-261, 2022 Mar 01.
Article in English | MEDLINE | ID: covidwho-1864300

ABSTRACT

IMPORTANCE: Childhood community-acquired pneumonia (CAP) is usually treated with 10 days of antibiotics. Shorter courses may be effective with fewer adverse effects and decreased potential for antibiotic resistance. OBJECTIVE: To compare a short (5-day) vs standard (10-day) antibiotic treatment strategy for CAP in young children. DESIGN, SETTING, AND PARTICIPANTS: Randomized double-blind placebo-controlled clinical trial in outpatient clinic, urgent care, or emergency settings in 8 US cities. A total of 380 healthy children aged 6 to 71 months with nonsevere CAP demonstrating early clinical improvement were enrolled from December 2, 2016, to December 16, 2019. Data were analyzed from January to September 2020. INTERVENTION: On day 6 of their originally prescribed therapy, participants were randomized 1:1 to receive 5 days of matching placebo or 5 additional days of the same antibiotic. MAIN OUTCOMES AND MEASURES: The primary end point was the end-of-treatment response adjusted for duration of antibiotic risk (RADAR), a composite end point that ranks each child's clinical response, resolution of symptoms, and antibiotic-associated adverse effects in an ordinal desirability of outcome ranking (DOOR). Within each DOOR rank, participants were further ranked by the number of antibiotic days, assuming that shorter antibiotic durations were more desirable. Using RADAR, the probability of a more desirable outcome was estimated for the short- vs standard-course strategy. In a subset of children, throat swabs were collected between study days 19 and 25 to quantify antibiotic resistance genes in oropharyngeal flora. RESULTS: A total of 380 children (189 randomized to short course and 191 randomized to standard course) made up the study population. The mean (SD) age was 35.7 (17.2) months, and 194 participants (51%) were male. Of the included children, 8 were Asian, 99 were Black or African American, 234 were White, 32 were multiracial, and 7 were of unknown or unreported race; 33 were Hispanic or Latino, 344 were not Hispanic or Latino, and 3 were of unknown or unreported ethnicity. There were no differences between strategies in the DOOR or its individual components. Fewer than 10% of children in either strategy had an inadequate clinical response. The short-course strategy had a 69% (95% CI, 63-75) probability of a more desirable RADAR outcome compared with the standard-course strategy. A total of 171 children were included in the resistome analysis. The median (range) number of antibiotic resistance genes per prokaryotic cell (RGPC) was significantly lower in the short-course strategy compared with the standard-course strategy for total RGPC (1.17 [0.35-2.43] vs 1.33 [0.46-11.08]; P = .01) and ß-lactamase RGPC (0.55 [0.18-1.24] vs 0.60 [0.21-2.45]; P = .03). CONCLUSIONS AND RELEVANCE: In this study, among children responding to initial treatment for outpatient CAP, a 5-day antibiotic strategy was superior to a 10-day strategy. The shortened approach resulted in similar clinical response and antibiotic-associated adverse effects, while reducing antibiotic exposure and resistance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02891915.


Subject(s)
Community-Acquired Infections , Pneumonia , Anti-Bacterial Agents/adverse effects , Child , Child, Preschool , Community-Acquired Infections/drug therapy , Double-Blind Method , Female , Humans , Male , Outpatients , Pneumonia/drug therapy
16.
Niger J Clin Pract ; 25(5): 702-709, 2022 May.
Article in English | MEDLINE | ID: covidwho-1863109

ABSTRACT

Background: Epidemiology of nosocomial infections may show variability because of under-estimation of infection control measures (ICMs) in coronavirus disease 19 (COVID-19) outbreak. Aim: To investigate the Acinetobacter bacteremia outbreak developed in an intensive care unit (ICU) between March 20 to May 15, 2020, examine the risk factors, and re-evaluate ICM retrospectively. Material and Methods: A retrospective cohort analysis was conducted to determine the risk factors, pulsed field gel electrophoresis (PFGE) was performed for analysis of the outbreak, ICM practices were observed by a team, and infection control interventions were undertaken. Results: Acinetobacter bacteremia developed in 17 patients (21.5%) within 79 COVID-19 patients included in the study. The mean age of the bacteremic patients was 67.3 (SD = 14.82) years, and 82.4% of them were male; of these, 15 died, leading to 88.2% mortality. The bacteremia rate was higher compared with a 14-month period preceding the COVID-19 pandemic (17/79 versus 12/580 patients, respectively). PFGE revealed that the outbreak was polyclonal. On multi-variate analysis, the bacteremia development rate was 13.7 and 5.06 times higher with central venous catheter (CVC) use and in patients with chronic obstructive pulmonary disease (COPD), respectively. The mortality rate was higher in bacteremic patients (p = 0.0016). It was observed that ICMs were not followed completely, especially change of gloves and hand hygiene. Contamination of A. baumannii was observed in 38% of the gloves. Conclusion: COPD and CVC use were determined as risk factors for Acinetobacter bacteremia development, and failures in ICM may have led to cross-contamination of endemic A. baumannii. The outbreak could be controlled within 3 weeks of interventions.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , Bacteremia , COVID-19 , Cross Infection , Pulmonary Disease, Chronic Obstructive , Acinetobacter Infections/drug therapy , Acinetobacter Infections/epidemiology , Aged , Anti-Bacterial Agents/pharmacology , Bacteremia/drug therapy , Bacteremia/epidemiology , COVID-19/epidemiology , Cross Infection/epidemiology , Disease Outbreaks , Drug Resistance, Multiple, Bacterial , Female , Humans , Intensive Care Units , Male , Pandemics , Pulmonary Disease, Chronic Obstructive/epidemiology , Retrospective Studies
17.
Antimicrob Resist Infect Control ; 11(1): 74, 2022 05 21.
Article in English | MEDLINE | ID: covidwho-1862157

ABSTRACT

BACKGROUND: Patients hospitalised for COVID-19 may present with or acquire bacterial or fungal infections that can affect the course of the disease. The aim of this study was to describe the microbiological characteristics of laboratory-confirmed infections in hospitalised patients with severe COVID-19. METHODS: We reviewed the hospital charts of a sample of patients deceased with COVID-19 from the Italian National COVID-19 Surveillance, who had laboratory-confirmed bacterial or fungal bloodstream infections (BSI) or lower respiratory tract infections (LRTI), evaluating the pathogens responsible for the infections and their antimicrobial susceptibility. RESULTS: Among 157 patients with infections hospitalised from February 2020 to April 2021, 28 (17.8%) had co-infections (≤ 48 h from admission) and 138 (87.9%) had secondary infections (> 48 h). Most infections were bacterial; LRTI were more frequent than BSI. The most common co-infection was pneumococcal LRTI. In secondary infections, Enterococci were the most frequently recovered pathogens in BSI (21.7% of patients), followed by Enterobacterales, mainly K. pneumoniae, while LRTI were mostly associated with Gram-negative bacteria, firstly Enterobacterales (27.4% of patients, K. pneumoniae 15.3%), followed by A. baumannii (19.1%). Fungal infections, both BSI and LRTI, were mostly due to C. albicans. Antibiotic resistance rates were extremely high in Gram-negative bacteria, with almost all A. baumannii isolates resistant to carbapenems (95.5%), and K. pneumoniae and P. aeruginosa showing carbapenem resistance rates of 59.5% and 34.6%, respectively. CONCLUSIONS: In hospitalised patients with severe COVID-19, secondary infections are considerably more common than co-infections, and are mostly due to Gram-negative bacterial pathogens showing a very high rate of antibiotic resistance.


Subject(s)
Anti-Bacterial Agents , Bacteremia , COVID-19 , Coinfection , Drug Resistance, Microbial , Fungemia , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteremia/complications , Bacteremia/drug therapy , Bacteremia/microbiology , COVID-19/complications , Coinfection/drug therapy , Coinfection/epidemiology , Coinfection/microbiology , Fungemia/complications , Fungemia/drug therapy , Fungemia/microbiology , Hospitalization/statistics & numerical data , Humans , Italy/epidemiology , Population Surveillance , Respiratory Tract Infections/complications , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology
18.
BMC Infect Dis ; 22(1): 492, 2022 May 24.
Article in English | MEDLINE | ID: covidwho-1862110

ABSTRACT

BACKGROUND: Increased and inappropriate antimicrobial use are the key drivers of the emergence of antimicrobial resistance, and there have been widespread concerns around potential antimicrobial misuse, overuse and their consequences during the COVID-19 pandemic. To better understand the impact of the pandemic on antimicrobial use, particularly in light of the resurgence of COVID-19 cases since the summer of 2020, we assessed trends in antimicrobial prescription fills and hospital requisitions in Sweden during 2020 against those of preceding years. METHODS: We performed a descriptive study using population-based data from the Swedish Prescribed Drug Register and the Swedish e-Health Agency. The weekly number of prescriptions filled and the total volume sold to inpatient care institutions in defined daily doses (DDDs) per 1000 inhabitants for systemic antibacterials (Anatomical Therapeutic Chemical therapeutic subgroup J01 excluding J01XX), antimycotics (J02), antivirals (J05) and antiprotozoals (P01) were computed and evaluated from time series graphs. A time series linear regression with ordinary least squares (OLS) estimation was used to model 2015-2019 data and predict the expected number of prescriptions filled and volumes sold in DDDs per 1000 inhabitants during 2020 with 95% confidence limits. RESULTS: From mid-March 2020, the weekly rate of antibiotic and antiprotozoal prescriptions filled plummeted to unprecedentedly low levels for the rest of the year; while unprecedentedly high numbers of antiviral prescriptions were filled weekly between mid-February and mid-March 2020. There was a net reduction in annual dispensing of antibiotics by 17%; of antiprotozoals by 21%; and of antivirals by 0.3% during 2020 compared to 2019. Inpatient care requisitions of antiprotozoals and antibiotics surged to 6-year highs during March 2020, resulting in a 127% increase in DDDs of antiprotozoals sold from 2019. The volume of antibiotics and antivirals sold to inpatient care institutions in 2020 decreased by 3% and 13% compared to 2019, respectively. CONCLUSIONS: The overall decline in antimicrobial prescriptions filled in Sweden during 2020 were in part, collateral dividends of the COVID-19 pandemic.


Subject(s)
Anti-Infective Agents , COVID-19 , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/epidemiology , Drug Prescriptions , Humans , Inpatients , Pandemics , Sweden/epidemiology
19.
Nanomedicine (Lond) ; 17(11): 793-812, 2022 May.
Article in English | MEDLINE | ID: covidwho-1855274

ABSTRACT

Infectious diseases are prevalent and have contributed to high morbidity rates by creating havoc like the COVID-19, 1918 influenza and Black Death (the plague) pandemics. Antimicrobial resistance, adverse effects, the emergence of co-infections and the high cost of antimicrobial therapies are major threats to the health of people worldwide while impacting overall healthcare and socioeconomic development. One of the most common ways to address this issue lies in improving existing antimicrobial drug-delivery systems. Nanoemulsions and their modified forms have been successfully employed for the delivery of antimicrobials to treat infectious diseases. In this article, the authors comprehensively reviewed how nanoemulsion-based formulation systems are shifting the paradigm for therapeutics and diagnosis of infectious diseases.


Subject(s)
Anti-Infective Agents , COVID-19 , Communicable Diseases , Anti-Bacterial Agents , COVID-19/drug therapy , Communicable Diseases/drug therapy , Emulsions , Humans
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