18 Questions
What is the primary action of trimethoprim on bacterial cells?
Inhibiting the dihydrofolate reductase
What is the result of the overexpression of a non-specific dihydrofolate reductase in bacteria during trimethoprim therapy?
Loss of ranoxacin from the cytoplasm
What is the effect of increasing plasma levels of trimethoprim on the other antibiotics?
Rarely described antagonistic activity
What is the advantage of using high-dose trimethoprim in combination with other antibiotics?
It is a cheap and effective alternative
What is the mechanism of action of rifampicin against A.baumannii?
Inhibiting the bacterial DNA-dependent RNA polymerase
What is the effect of combining rifampicin with other antibiotics against A.baumannii?
It potentiates the activity of most of the other antibiotics
What is the primary advantage of using colistin plus high-dose trimethoprim compared to colistin monotherapy?
It has a higher cure rate of A.baumannii bloodstream infections
What is the characteristic of extensively drug-resistant A.baumannii (CRAB) infections?
They have a poor prognosis, often necessitating last-line compounds
What is a characteristic of rifampicin's elimination pattern in patients with kidney or liver dysfunction?
It is not altered
What is the current global situation regarding antibiotic resistance?
It is a rapidly expanding public health crisis
What is a major challenge in treating MDR Acinetobacter baumannii?
There are fewer therapeutic options
What is the current status of commercial methods for rapid antimicrobial susceptibility testing of A.baumannii?
There are no commercially available methods
Why is CRAB more difficult to eradicate than CRKP?
CRAB is more difficult to diagnose
What is the proposed source of HAB?
Periodontal disease and invasive devices
What is the significance of CRAB's ability to colonize the oropharynx and gastrointestinal tract?
It is significant for understanding the spectrum of infections
What is the current focus of policymakers, professionals, patients, and the public regarding MDR Gram-negative infections?
Treatment options, hygiene, and prevention measures
What is the impact of rifampicin on MDR A.baumannii?
It is effective against some MDR A.baumannii, but not all
Why are outbreaks of CRAB usually caused by a wide epidemiological variety of strains?
Because the strains make up a high percentage of the unit's flora
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
Trimethoprim is an inhibitor of dihydrofolate reductase, effective against rapidly dividing bacteria. Resistance can emerge due to overexpression of a non-specific dihydrofolate reductase, leading to a loss of effectiveness.
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