The Introduction of Antimicrobial Agents in Resource-Constrained Countries: Impact on the Emergence of Resistance

Author(s):  
Carlos Franco-Paredes ◽  
Jose Ignacio Santos-Preciado
2018 ◽  
Vol 57 (1) ◽  
Author(s):  
Shannon Katiyo ◽  
Berit Muller-Pebody ◽  
Mehdi Minaji ◽  
David Powell ◽  
Alan P. Johnson ◽  
...  

ABSTRACT Nontyphoidal Salmonella (NTS) bacteremia causes hospitalization and high morbidity and mortality. We linked Gastrointestinal Bacteria Reference Unit (GBRU) data to the Hospital Episode Statistics (HES) data set to study the trends and outcomes of NTS bacteremias in England between 2004 and 2015. All confirmed NTS isolates from blood from England submitted to GBRU between 1 January 2004 and 31 December 2015 were deterministically linked to HES records. Adjusted odds ratios (AOR), proportions, and confidence intervals (CI) were calculated to describe differences in age, sex, antibiotic resistance patterns, and serotypes over time. Males, neonates, and adults above 65 years were more likely to have NTS bacteremia (AOR, 1.54 [95% CI, 1.46 to 1.67]; 2.57 [95% CI, 1.43 to 4.60]; and 3.56 [95% CI, 3.25 to 3.90], respectively). Proportions of bacteremia increased from 1.41% in 2004 to 2.67% in 2015. Thirty-four percent of all blood isolates were resistant to a first-line antibiotic, and 1,397 (56%) blood isolates were linked to an HES record. Of the patients with NTS bacteremia, 969 (69%) had a cardiovascular condition and 155 (12%) patients died, out of which 120 (77%) patients were age 65 years and above. NTS bacteremia mainly affects older people with comorbidities placing them at increased risk of prolonged hospital stay and death. Resistance of invasive NTS to first-line antimicrobial agents appeared to be stable in England, but the emergence of resistance to last-resort antibiotics, such as colistin, requires careful monitoring.


2021 ◽  
Author(s):  
Felipe de Paula Nogueira Cruz ◽  
Andréa Cristina Bogas ◽  
Cristina Paiva de Sousa

There has been an important increase in the emergence of resistance in microbial population worldwide. This trajectory needs, necessarily new approaches to treat infectious diseases. The ability to detect and prevent the evolutionary trajectories of microbial resistance would be of value. Photodynamic inactivation (PDI) represents an efficient alternative treatment for diseases caused by viruses, which can cause infections well documented in various mammals. PDI can kill cells after exposure with the appropriate photosensitizer (PS), light of adequate wavelength combined with the presence of oxygen, without inducing resistance. Cytotoxic reactive species formed interaction with vital biomolecules leading to irreversible microbial inactivation. Bacteriophages can act on delivering antimicrobial agents into bacteria, which consist in a likely instrument for the treatment of infectious diseases. Non-enveloped bacteriophages are more difficult to tolerate photoinactivation than enveloped phages, which makes them an important model tool to evaluate the efficiency of PDI therapy against viruses that cause diseases in humans. Combination of photosensitizers and bacteriophage therapy can be employed to eradicate biofilms, contributing to control of infections also caused by drug-resistant bacteria.


2013 ◽  
Vol 57 (10) ◽  
pp. 4794-4800 ◽  
Author(s):  
Patrick A. M. Jansen ◽  
Pedro H. H. Hermkens ◽  
Patrick L. J. M. Zeeuwen ◽  
Peter N. M. Botman ◽  
Richard H. Blaauw ◽  
...  

ABSTRACTThe emergence of resistance against current antibiotics calls for the development of new compounds to treat infectious diseases. Synthetic pantothenamides are pantothenate analogs that possess broad-spectrum antibacterial activityin vitroin minimal media. Pantothenamides were shown to be substrates of the bacterial coenzyme A (CoA) biosynthetic pathway, causing cellular CoA depletion and interference with fatty acid synthesis. In spite of their potential use and selectivity for bacterial metabolic routes, these compounds have never made it to the clinic. In the present study, we show that pantothenamides are not active as antibiotics in the presence of serum, and we found that they were hydrolyzed by ubiquitous pantetheinases of the vanin family. To address this further, we synthesized a series of pantetheinase inhibitors based on a pantothenate scaffold that inhibited serum pantetheinase activity in the nanomolar range. Mass spectrometric analysis showed that addition of these pantetheinase inhibitors prevented hydrolysis of pantothenamides by serum. We found that combinations of these novel pantetheinase inhibitors and prototypic pantothenamides like N5-Pan and N7-Pan exerted antimicrobial activityin vitro, particularly against Gram-positive bacteria (Staphylococcus aureus,Staphylococcus epidermidis,Streptococcus pneumoniae, andStreptococcus pyogenes) even in the presence of serum. These results indicate that pantothenamides, when protected against degradation by host pantetheinases, are potentially useful antimicrobial agents.


1996 ◽  
Vol 7 (1_suppl) ◽  
pp. 23-27 ◽  
Author(s):  
L S Young

The most common pathogens involved in disseminated bacterial infection in people with acquired immunodeficiency syndrome (AIDS) are organisms of the Mycobacterium avium-intracellulare complex (MAC). Azithromycin and clarithromycin, a new azalide and macrolide, respectively, are among the most potent monotherapies for MAC bacteraemia, although many bloodstream isolates demonstrate increased minimum inhibitory concentrations after 4 months of treatment. Current recommended prophylaxis, based on the results of two randomized, double-blind, prospective studies, is rifabutin 300 mg daily for people with AIDS with <100 CD4 lymphocytes/mm3. In the beige mouse model, we have shown that both azithromycin and clarithromycin prevent MAC bacteraemia following repetitive oral challenge. Clinical trials are now underway to confirm these effects in man; comparative treatments include placebo, rifabutin and an azalide/macrolide plus rifabutin. While combinations might be more effective and reduce the emergence of resistance, the spectre of cytochrome P-450 drug interactions necessitates careful study before combination prophylactic approaches are accepted. Such interactions are associated with rifabutin and some macrolides, although azithromycin may be less problematic in this respect as it appears to have little potential to interact with other antimicrobial agents.


Author(s):  
Bhagyashri D. Rajopadhye ◽  
Sonali H. Palkar ◽  
Vijaya A. Pandit ◽  
Priti P. Dhande ◽  
Mahadevan Kumar ◽  
...  

Background: The emergence of antimicrobial resistance is a worldwide challenge threatening to negate the gains made by discovery of antimicrobial agents (AMAs).  Antimicrobial Stewardship Program (ASP) is an important strategy for ensuring appropriate use of AMAs and controlling emergence of antibiotic resistance. Implementation of ASP must start with assessment of the current state of antimicrobial use. This study was therefore conducted to assess the prevalent prescribing patterns in a tertiary care hospital and identify gaps which warrant corrective intervention.Methods: This prospective pilot study presents analysis of the first 30 Patients from the medicine ward prescribed at least one antimicrobial agent during the two months of study period. Relevant data was collected in AMA record form. Appropriateness of AMAs was analyzed regarding selection as well as administration protocol as per the hospital antibiotic policy.Results: Out of the 60 AMAs prescribed to these patients, most commonly prescribed were cephalosporins (63.3%), anti-amoebics (26.6%) and macrolides (23.3%). Common diseases involved were urinary tract infection, acute gastroenteritis, sepsis and lower respiratory tract infections.  Use of AMAs was found to be appropriate for the indication in 42 %, dose in 97%, duration 60 %, route 93% and frequency 90 %.Conclusions: This gap between the appropriate and the actual practice use of AMAs indicates an urgent need of rigorous implementation of ASP in order to avoid emergence of resistance and to conserve the sensitivity to the available AMAs.


Recently, Helicobacter pylori has been connected to more than 80% of chronic active gastritis and other gastroduodenal diseases worldwide. Treatment of H. pylori is routinely dependent on the use of multiple antimicrobial agents however, recent data showed the emergence of resistance among clinical strains especially against metronidazole and clarithromycin. This study was conducted to investigate the rate of resistance to different antibiotics that are routinely used in the first line and second line therapies including ciprofloxacin and levofloxacin, tetracycline, amoxicillin, clarithromycin and metronidazole among H. pylori strains isolated from patients with gastroduodenal diseases in Jordan. Both antral and corpus mucosal biopsies from the stomach of patients with positive results of H. pylori stool antigen and urease breath tests were used for the isolation of H. pylori on selective culture media. The standard agar diffusion method was performed to determine the sensitivity of H. pylori clinical isolates against ciprofloxacin and levofloxacin according to CLSI. Among 62 H. pylori clinical strains isolated from gastric biopsies, 21% and 11% were resistant to levofloxacin and ciprofloxacin respectively. Resistance to metronidazole and clarithromycin was found in 90% and 11% respectively. No resistance was observed against amoxicillin, tetracycline and gemifloxacin. The following MIC90 (mg/L) of resistant strains results were obtained at neutral pH 7.3, 64 for metronidazole, 2 for clarithromycin, 2 for ciprofloxacin and 1 for levofloxacin. The present study reported the emergence of increased resistance of fluoroquinolones among H. pylori clinical isolates in Jordan. Concern should be taken into consideration when triple and quadruple therapy regimens are applied for the management of H. pylori infections in our region


2003 ◽  
Vol 47 (2) ◽  
pp. 563-567 ◽  
Author(s):  
Lin-Hui Su ◽  
Cheng-Hsun Chiu ◽  
Chishih Chu ◽  
Mei-Hui Wang ◽  
Ju-Hsin Chia ◽  
...  

ABSTRACT The emergence of resistance to antimicrobial agents within the salmonellas is a worldwide and severe problem. A case of treatment failure due to the emergence of resistance to ceftriaxone in Salmonella enterica serotype Anatum was studied. S. enterica serotype Anatum and Escherichia coli, both of which are susceptible to ceftriaxone, were initially isolated from a diabetic patient hospitalized for the treatment of wound and urinary tract infections. Resistant S. enterica serotype Anatum and E. coli strains were isolated concomitantly 2 weeks after the initiation of ceftriaxone therapy. The patient eventually died of a sepsis caused by the ceftriaxone-resistant salmonella. PCR, nucleotide sequence analysis, and DNA-DNA hybridization identified a bla CTX-M-3 gene located on a 95.1-kb plasmid from the ceftriaxone-resistant isolates of S. enterica serotype Anatum and E. coli. The plasmid was proved to be conjugative. Molecular fingerprinting showed that the susceptible and resistant strains were genetically indistinguishable. The emergence of resistance to ceftriaxone in S. enterica serotype Anatum was due to the in vivo acquisition of a plasmid containing the bla CTX-M-3 gene and was the cause for treatment failure in this patient.


2007 ◽  
Vol 52 (3) ◽  
pp. 995-1000 ◽  
Author(s):  
Sang-Ho Choi ◽  
Jung Eun Lee ◽  
Su Jin Park ◽  
Seong-Ho Choi ◽  
Sang-Oh Lee ◽  
...  

ABSTRACT Enterobacter spp., Serratia marcescens, Citrobacter freundii, and Morganella morganii are characterized by chromosomally encoded AmpC β-lactamases and possess the ability to develop resistance upon exposure to broad-spectrum cephalosporins. To determine the incidences of the emergence of resistance during antimicrobial therapy for infections caused by these organisms and the effect of the emergence of resistance on patient outcomes, all patients who were admitted to the Asan Medical Center (Seoul, Republic of Korea) from January 2005 to June 2006 and whose clinical specimens yielded Enterobacter spp., S. marcescens, C. freundii, or M. morganii were monitored prospectively. The main end point was the emergence of resistance during antimicrobial therapy. A total of 732 patients with infections were included for analysis. The overall incidence of the emergence of antimicrobial resistance during antimicrobial therapy was 1.9% (14/732). Resistance to broad-spectrum cephalosporins, cefepime, extended-spectrum penicillin, carbapenem, fluoroquinolones, and aminoglycosides emerged during treatment in 5.0% (11/218), 0% (0/20), 2.0% (2/100), 0% (0/226), 0% (0/153), and 1.1% (1/89) of patients, respectively. The emergence of resistance to broad-spectrum cephalosporins occurred more often in Enterobacter spp. (8.3%, 10/121) than in C. freundii (2.6%, 1/39), S. marcescens (0%, 0/37), or M. morganii (0%, 0/21). Biliary tract infection associated with malignant bile duct invasion was significantly associated with the emergence of resistance to broad-spectrum cephalosporins (P = 0.024 at a significance level of 0.042, by use of the Bonferroni correction). Only 1 of the 14 patients whose isolates developed resistance during antimicrobial therapy died. The emergence of resistance was more frequently associated with broad-spectrum cephalosporins than with the other antimicrobial agents tested, especially in Enterobacter spp. However, the emergence of resistance was associated with a low risk of mortality.


2001 ◽  
Vol 45 (6) ◽  
pp. 1607-1614 ◽  
Author(s):  
Kevin A. Nash

ABSTRACT The emergence of antibiotic resistance in mycobacteria involves the selection of mutant variants within a susceptible bacterial population. However, it is unclear whether antimycobacterial drugs act just as selective agents or can influence the rate of appearance of resistant mutants. The present study was initiated to address this issue by monitoring the effects of antimicrobial agents on the appearance and growth of clarithromycin (CLR)-resistant (CLRr) bacilli in broth cultures of Mycobacterium avium. Preexposure ofM. avium to CLR had a significant dose effect on the emergence of resistance, with concentrations of 4 to 8 μg/ml resulting in a maximal (∼104-fold) increase in the number of CLRr bacilli after a 4-day incubation. In addition, a dose effect was found with azithromycin. The use of combinations of CLR with either ethambutol (EMB) or rifabutin (RFB) resulted in fewer resistant bacilli compared to the use of CLR alone. The lowest active concentration of EMB (4 μg/ml) was equivalent to the EMB MIC (4 to 8 μg/ml) for the parental CLRs strain and the emergent CLRr variants, and thus, the antiresistance effect was probably the result of the bacteriostatic effect of EMB on CLRr bacilli. However, RFB was an order of magnitude more active (0.05 μg/ml) at reducing resistance than suggested by the MIC of this agent (0.5 to 1 μg/ml). These results indicate that the emergence of resistance was not simply the selection of a preexisting subpopulation of resistant bacilli. Further analysis suggested that early events in the emergence of resistance involved organisms (progenitors) that acquired a resistance phenotype. In addition, the progenitors appeared to be in a transient state, able to develop into a stable resistant lineage in the presence of CLR, or able to revert to the wild type in nonselective conditions.


Author(s):  
A. U. Hassan ◽  
A. H. Madu ◽  
U. O. Ozojiofor ◽  
A. H. Galadanci ◽  
I. B. Mato ◽  
...  

Increasing emergence of resistance to antibiotics by pathogenic microorganisms worldwide necessitates the need for finding new antimicrobial agents with minimal resistance and side effects. This study was carried out to investigate the phytochemical content and antimicrobial activities of two ethno-medicinal plants namely: Cymbopogon citratus and Ximenia Americana. Methanol and aqueous were used as solvent for a soxhlet and aqueous percolation extraction techniques to obtain the crude extracts of the named plant parts. Tannins, steroids, reducing sugars, tritapenoids and Flavonoids were found present in these plant extracts. GC-MS analysis done in this study indicates the presence of some basic phenolic compounds, such as; Cyclohexane-1-3,5-trione & 2-phenyl-1,4-benzopyrone, in the C. citratus extract and methyl guanidine & 3-meyhylheptyl acetate in the X. americana extract, which have been attributed with numerous antimicrobial effects onmicrobial pathogens. Using an agar well diffusion bioassay technique the C. citratus extracts shows; both the extracts are active against E. coli and P. aeroginosa. While X. americana extracts shows a higher activity against C. albican. However the MIC/MBC/MFC of all the extracts shows that known of the extracts has an active viability below 12.5µg/ml.


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