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1/13
Attending: Why don’t we use cipro to treat PNA?
Intern: B/c it doesn’t penetrate the lung?
Attending: Right! It isn’t a “respiratory fluoroquinolone”.
ಠ_ಠ…well yes, but no. So close.
@tweetorial #medtwitter @CuriousClinPod @AvrahamCooperMD @HannahRAbrams @tony_breu
Attending: Why don’t we use cipro to treat PNA?
Intern: B/c it doesn’t penetrate the lung?
Attending: Right! It isn’t a “respiratory fluoroquinolone”.
ಠ_ಠ…well yes, but no. So close.
@tweetorial #medtwitter @CuriousClinPod @AvrahamCooperMD @HannahRAbrams @tony_breu
2/13
Nearly all quinolone antibiotics used are fluoroquinolones—a fluorine atom attached to a bicyclic core structure related to 4-quinolone.
http://pubmed.ncbi.nlm.nih.gov/2679364/
Nearly all quinolone antibiotics used are fluoroquinolones—a fluorine atom attached to a bicyclic core structure related to 4-quinolone.
http://pubmed.ncbi.nlm.nih.gov/2679364/
3/13
Quinolones are broad-spectrum antibacterial agents that interfere with DNA replication by inhibiting topoisomerase IV and DNA gyrase. Specifically two subunits of gyrase (gyrA and gyrB), and two subunits of topoisomerase IV (parC and parE).
Quinolones are broad-spectrum antibacterial agents that interfere with DNA replication by inhibiting topoisomerase IV and DNA gyrase. Specifically two subunits of gyrase (gyrA and gyrB), and two subunits of topoisomerase IV (parC and parE).
4/13
Maybe not thought of as much as with cephalosporins, but fluoroquinolones can be classified into generations as well, based loosely on their spectrum of coverage (1st/2nd gen largely active against gram-negs, 3rd/4th gen have increased gram-pos and anaerobic activity).
Maybe not thought of as much as with cephalosporins, but fluoroquinolones can be classified into generations as well, based loosely on their spectrum of coverage (1st/2nd gen largely active against gram-negs, 3rd/4th gen have increased gram-pos and anaerobic activity).
5/13
Cipro binds exclusively with topoisomerase IV, which includes the parC subunit. In a study looking at fluoroquinolone resistance in S. pneumoniae in the US between 1994-2000, 49/164 (29.9%) unique isolates harbored at least one mutation in the parC or gyrA genes.
Cipro binds exclusively with topoisomerase IV, which includes the parC subunit. In a study looking at fluoroquinolone resistance in S. pneumoniae in the US between 1994-2000, 49/164 (29.9%) unique isolates harbored at least one mutation in the parC or gyrA genes.
6/13
67.3% of the quinolone resistance mutation containing isolates involved the parC locus only. The study also commented that there was no evidence of resistance rate changes over this 5-year time period.
67.3% of the quinolone resistance mutation containing isolates involved the parC locus only. The study also commented that there was no evidence of resistance rate changes over this 5-year time period.
7/13
Resistance accumulates in a stepwise fashion. For instance, isolates with mutations in both parC and gyrA tend to be resistant to all fluoroquinolones.
Resistance accumulates in a stepwise fashion. For instance, isolates with mutations in both parC and gyrA tend to be resistant to all fluoroquinolones.
8/13
In this same data set, the overall average ciprofloxacin resistance of the total sampled S. pneumoniae clinical isolates (n=4,650, which includes isolates not found to have any identified quinolone resistance mutations), was found to be only 1.4%.
In this same data set, the overall average ciprofloxacin resistance of the total sampled S. pneumoniae clinical isolates (n=4,650, which includes isolates not found to have any identified quinolone resistance mutations), was found to be only 1.4%.
9/13
So…using ciprofloxacin to treat CAP (or at least S. pneumo) might work, but expect a high rate of treatment failure, especially for those with certain risk factors.
So…using ciprofloxacin to treat CAP (or at least S. pneumo) might work, but expect a high rate of treatment failure, especially for those with certain risk factors.
10/13
On the other hand, levofloxacin, moxifloxacin, and gemifloxacin bind both topoisomerase IV and gyrase.
Because of the stepwise development of resistance, pneumococcal isolates need to accumulate more mutations to be resistant against higher generation fluoroquinolones.
On the other hand, levofloxacin, moxifloxacin, and gemifloxacin bind both topoisomerase IV and gyrase.
Because of the stepwise development of resistance, pneumococcal isolates need to accumulate more mutations to be resistant against higher generation fluoroquinolones.
11/13
So…ciprofloxacin actually DOES get into the lung?
Yes.
So…ciprofloxacin actually DOES get into the lung?
Yes.
12/13
Several studies from the 1990’s using high-performance liquid chromatography demonstrate ciprofloxacin’s lung tissue concentration to be AT LEAST 2-3x that of the plasma concentration.
Several studies from the 1990’s using high-performance liquid chromatography demonstrate ciprofloxacin’s lung tissue concentration to be AT LEAST 2-3x that of the plasma concentration.
13/13
In summary…
Ciprofloxacin penetrates the lung tissue just fine.
In summary…
Ciprofloxacin penetrates the lung tissue just fine.
