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Questions and Answers
What is the primary action of trimethoprim on bacterial cells?
What is the primary action of trimethoprim on bacterial cells?
- Inhibiting the dihydrofolate reductase (correct)
- Inhibiting the bacterial cell wall formation
- Inhibiting the DNA-dependent RNA polymerase
- Inhibiting the bacterial replication process
What is the result of the overexpression of a non-specific dihydrofolate reductase in bacteria during trimethoprim therapy?
What is the result of the overexpression of a non-specific dihydrofolate reductase in bacteria during trimethoprim therapy?
- Increased potency of colistin
- Increased resistance to rifampicin
- Loss of ranoxacin from the cytoplasm (correct)
- Increased susceptibility to trimethoprim
What is the effect of increasing plasma levels of trimethoprim on the other antibiotics?
What is the effect of increasing plasma levels of trimethoprim on the other antibiotics?
- No effect on the other antibiotics
- Increased synergistic activity
- Decreased antagonistic activity
- Rarely described antagonistic activity (correct)
What is the advantage of using high-dose trimethoprim in combination with other antibiotics?
What is the advantage of using high-dose trimethoprim in combination with other antibiotics?
What is the mechanism of action of rifampicin against A.baumannii?
What is the mechanism of action of rifampicin against A.baumannii?
What is the effect of combining rifampicin with other antibiotics against A.baumannii?
What is the effect of combining rifampicin with other antibiotics against A.baumannii?
What is the primary advantage of using colistin plus high-dose trimethoprim compared to colistin monotherapy?
What is the primary advantage of using colistin plus high-dose trimethoprim compared to colistin monotherapy?
What is the characteristic of extensively drug-resistant A.baumannii (CRAB) infections?
What is the characteristic of extensively drug-resistant A.baumannii (CRAB) infections?
What is a characteristic of rifampicin's elimination pattern in patients with kidney or liver dysfunction?
What is a characteristic of rifampicin's elimination pattern in patients with kidney or liver dysfunction?
What is the current global situation regarding antibiotic resistance?
What is the current global situation regarding antibiotic resistance?
What is a major challenge in treating MDR Acinetobacter baumannii?
What is a major challenge in treating MDR Acinetobacter baumannii?
What is the current status of commercial methods for rapid antimicrobial susceptibility testing of A.baumannii?
What is the current status of commercial methods for rapid antimicrobial susceptibility testing of A.baumannii?
Why is CRAB more difficult to eradicate than CRKP?
Why is CRAB more difficult to eradicate than CRKP?
What is the proposed source of HAB?
What is the proposed source of HAB?
What is the significance of CRAB's ability to colonize the oropharynx and gastrointestinal tract?
What is the significance of CRAB's ability to colonize the oropharynx and gastrointestinal tract?
What is the current focus of policymakers, professionals, patients, and the public regarding MDR Gram-negative infections?
What is the current focus of policymakers, professionals, patients, and the public regarding MDR Gram-negative infections?
What is the impact of rifampicin on MDR A.baumannii?
What is the impact of rifampicin on MDR A.baumannii?
Why are outbreaks of CRAB usually caused by a wide epidemiological variety of strains?
Why are outbreaks of CRAB usually caused by a wide epidemiological variety of strains?
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Study Notes
Trimethoprim
- Inhibits dihydrofolate reductase, targeting rapidly dividing subpopulation of bacteria
- Resistance can emerge due to overexpression of non-specific dihydrofolate reductase, leading to loss of ranoxacin from cytoplasm
- Optimal dose poorly defined, but 300mg 6-8 hourly with colistin and rifampicin has been used in outbreaks
- Higher doses can have negative effect on other antibiotics, but high-dose trimethoprim can be effective against A. baumannii bloodstream infections
Rifampicin
- Inhibits bacterial DNA-dependent RNA polymerase, active against rapidly dividing and slow-growing subpopulation of CRAB
- Potentiates activity of other antibiotics against A. baumannii
- Loading doses and maximum serum levels achieved after one dose, elimination pattern not altered in patients with kidney or liver dysfunction
- Renally eliminated, should not be used in prevention of CRAB colonization
- Small proportion of MDR A. baumannii have mutation of rpoB gene, resulting in reduced susceptibility to rifampicin
Acinetobacter baumannii
- Considered one of the most problematic non-fermenting Gram-negative pathogens in healthcare settings worldwide
- WHO has highlighted the need for creative solutions to alleviate negative consequences of MDR/Gram-negative bacterial infections
- Prudent use of existing antibiotics and prevention measures are urgently needed
Antibiotic Resistance
- Global public health crisis, rapidly expanding and complex
- Growing resistance, coupled with limited antibiotic development pipeline, is aggravating the situation
- Fewer therapeutic options for MDR Gram-negative infections, including A. baumannii
Diagnosis and Treatment
- Timely diagnosis is fundamental cornerstone of any infection
- No commercially available method for rapid antimicrobial susceptibility testing of A. baumannii
- Treatment options and hygiene measures are now prioritized on the political agenda
Clinical Impact
- CRAB is more difficult to eradicate than CRKP
- Data on clinical impact of discordant therapy in CRAB are limited and mostly retrospective
- Periodontal disease and invasive devices have been proposed as a source for HAB, which can also be transmitted indirectly through these systems
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