Quinolones resistance

It has been shown that an AAC enzyme variant (AAC (6 )-Ib-cr, cr for ciprofloxacin resistance) found in various Enterobacteriaceae is capable of A-acetylating fluoroquinolones with an unmodified piperazinyl substituent at the amino nitrogen. Although the increase in MIC is low, this plasmid encoded quinolone resistance determinant can augment further development of clinically relevant resistance. 

During lactation, all CDC first-line recommended therapies for gonorrhea (Table 44-5) are deemed compatible with breast-feeding by the AAP.14 Quinolone therapy is not recommended for women residing in California or Hawaii due to the increasing numbers of quinolone-resistant species.38... 

Thomson KS Minimizing quinolone resistance Are the new agents more or less likely to cause resistance J Antimicrob Chemother 2000 45 719-723. 

Regioselective hydrolysis of the diester 27 gave the 1,3-thiazetidine 28 where the thiazetidine ring is fused to a quinolone nucleus <99CPB1765>. Derivatives of the tricyclic system, e.g. 29, showed activity against gram-positive bacteria including quinolone-resistant MRS A <99H(51)2915>. 

Norfloxacin 400 mg or ciprofloxacin 500 mg orally twice daily x 3 days, or trimethoprim-sulfamethoxazole DS tablet orally twice daily x 3 days (in Mexico), or azithromycin 500 mg orally once daily x 3 days (only in areas of high prevalence of quinolone-resistant Campylobacter species, such as Thailand)... 

Goni-Urriza M, Arpin C, Capdepuy M et al (2002) Type II topoisomerase quinolone resistance-determining regions otAeromonas caviae,A. hydrophila, and A. sobria complexes and mutations associated with quinolone resistance. Antimicrob Agents Chemother 46(2) 350-359... 

Strahilevitz J, Jacoby GA, Hooper DC et al (2009) Plasmid-mediated quinolone resistance a multifaceted threat. Clin Microbiol Rev 22(4) 664—689... 

Cummings DE, Archer KF, Arriola DJ et al (2011) Broad dissemination of plasmid-mediated quinolone resistance genes in sediments of two urban coastal wetlands. Environ Sci Technol... 

Robicsek A, Jacoby GA, Hooper DC. The worldwide emergence of plasmid-mediated quinolone resistance. Lancet Infect Dis 2006 6-10 629-40. 

Treatment should be guided by the local or hospital resistance patterns. Extensive use of a quinolone for selective decontamination will increase the incidence of quinolone-resistant gram-negative pathogens. Alternative regimens for gut decontamination are oral colistin with an oral aminoglycoside such as neomycin. 

Bacteria acquire quinolone resistance by which of the following mechanisms ... 

B. Overproduction (A) of PABA is one of the resistance mechanisms of sulfonamides. Changes in the synthesis of DNA gyrases (B) is a well-described mechanism for quinolone resistance. Plasmid-mediated resistance (C) does not occur with quinolones. An active efflux system for transport of drug out of the cell has been described for quinolone resistance, but it is not plasmid mediated. Inhibition of structural blocks (D) in bacterial cell wall synthesis is a basic mechanism of action of p-lactam antibiotics. Inhibition of folic acid synthesis (E) by blocking different steps is the basic mechanism of action of sulfonamides. 

The effect of fluoroquinolone-resistance in Campylobacter on the clinical outcome of treatment with a fluoroquinolone is not yet clear. There are conflicting data on whether resistant Campylobacter can cause more severe disease. Although there has been little documented impact of this resistance on human health, current concern about the potential human health consequences if resistance were to increase and spread, is high. Tims, further research and data-gathering are essential to quantify this potential. In addition to quinolone resistance, coresistance... 

Hopkins KL, Davies RH, Threlfall EJ. Mechanisms of quinolone resistance in Escherichia coli and Salmonella recent developments. Int J Antimicrob Agents. 2005 25 358-373. 

The Court also documented the fact that levofloxacin was approximately two times more potent than the racemate ofloxacin. While this fact alone might not have been persuasive, it was persuasive to the court when coupled with the fact that levofloxacin is less toxic than ofloxacin. This appeared to contradict the conventional scientific wisdom in the art that the toxicity of the tricyclic quinolone antibiotics moved in parallel with the therapeutic activity.82 The Court also noted levofloxacin s unexpectedly higher effectiveness against S. pneumoniae when taking into account its exposure levels compared to oflaxocin as well as levofloxacin s unexpected potency against quinolone-resistant S. pneumoniae. 

The introduction of a fluorine atom at the C-l methyl group in the thiazetoquinolone 223 should enhance the in vitro and in vivo antibacterial activity against various bacteria including quinolone-resistant methicillin-resistant Staphylococcus aureus (MRSA) and also improve its bioavailability <1999CPB1765>. 

Plasmid-mediated resistance has so far evidently played no role in the spread of quinolone resistance and has seldom been detected [238], although plasmid-mediated resistance of K. pneumoniae and E. coli has been reported in China and the USA [239,240]. 

Jacoby GA. Quinolone resistance from a transferable plasmid. Lancet, 1998, 351 (9105), 797-799. 

Wang M, et al. Plasmid-mediated quinolone resistance in clinical isolates of Escherichia coli from Shanghai, China. Antimicrob. Agents Chemother., 2003, 47, 2242-2248. 

Lu T, Zhao X, Drlica K. Gatifloxacin activity against quinolone-resistant gyr-ase allele-specific enhancement of bacteriostatic and bactericidal activities by the C-8-methoxy group. Antimicrob. Agents Chemother., 1999, 43, 2969-2974. 

A suggested alternative is ofloxacin 400 mg orally twice daily plus oral metronidazole 400 mg twice daily, both for 14 days. This regimen is not recommended if the woman is at high risk of gonococcal PID because of increasing quinolone resistance of gonorrhoea infection in the UK. 

The problems of P-lactam and quinolone resistance in Neisseria gonorrhoeae are increasing, and selection of a particular drug will depend on sensitivity testing and a knowledge of resistance patterns in different geographical locations. Effective treatment... 

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