Quinolones: Are They Still Safe for Urinary Infection Therapy in Latin America?
- 1. Department of Infectious Diseases, Federal University of Rio Grande do Norte, Brazil
Abstract
Urinary tract infection is a common problem worldwide and susceptibility rates of bacteria to antibiotics are important in determining the treatment of choice and its duration. High resistance rates of uropathogens to quinolones in Latin America draws attention to the choice of these drugs on empirical treatments, especially in patients with pyelonephritis.
Keywords
Urinary tract infections; Antibacterial drug resistance; Enterobacteriaceae; Antibacterial agents
Citation
Cunha MA, Freitas MR (2018) Quinolones: Are They Still Safe for Urinary Infection Therapy in Latin America? J Urol Res 5(1): 1094.
ABBREVIATIONS
UTI: Urinary Tract Infection
INTRODUCTION
Urinary tract infection (UTI) is a common disease seen in community and nosocomial environments. It is defined by a tissue invasion of any part of urinary tract and it is more common in women, especially because a shorter urethra [1,2]. Usually, UTIs are classified in two groups: lower UTI, corresponding to infection on the bladder; upper UTI, frequently used as a synonym of pyelonephritis. Besides, UTIs are classified as uncomplicated and complicated, considering associated conditions that increases the risk of therapy failure, like diabetes, pregnancy, previous history of pyelonephritis, immunosuppression, among others. Frequently, UTIs are caused by only one agent and Escherichia coli is the pathogen most isolated around the world [2,3]. E. coli corresponds to 75 – 95% of microbial spectrum of UTI, followed by other species of Enterobacteriaceae family, such as Proteus mirabilis, Klebsiella pneumoniae, and Staphylococcus saprophyticus [3], with some particularities in proportion of pathogens and resistance profile, according to geographical region.
DISCUSSION AND CONCLUSION
Quinolones, especially ciprofloxacin, are drugs used largely in the UTI therapy, and have been shown to be effective since the beginning of their use in 80´s [4,5]. However, in the last decade, many studies have pointed to increasing of uropathogens resistance to quinolones, especially E. coli. The emergence of resistance to fluoroquinolones was recognized soon after the introduction of these drugs. Studies published in the early 1990s already demonstrated an increasing of resistance in some Europe regions [6,7]. A recent systematic review and metaanalysis [8] of observational studies including 53 studies showed and reaffirmed two important concepts: resistance varies significantly by region and, in addition, there was a significant rise in resistance on community-acquired E. coli UTI. Besides, resistance was significantly larger in developing countries. In this study, the community setting resistance to ciprofloxacin was 27%, which can be considered an alarming data, since this drug is frequently used in the clinical practice around the world and it is an option to complicated UTI, including those with sepsis signs [3].
In Latin America, the resistance scenario is also worrisome. In 2000, an antimicrobial surveillance program involving specimens from six Latin American countries (Brazil, Argentina, Chile, Colombia, Venezuela and Mexico) and including 434 bacterial isolates called attention to a high percentage of fluoroquinoloneresistant E. coli isolates (22.5%) in almost all Latin America centers [9]. The same surveillance program group published in 2006 new data about this issue. A total of 611 samples were collected from patients with community-acquired urinary tract infections. The data also demonstrated a high percentage of resistance rates (21.6%) of E. coli against the studied quinolones [10]. More recent studies also point to this problem. Cunha MA et al., assessed the susceptibility to antimicrobials of uropathogens isolated from community-acquired urinary tract infections in a northeastern Brazilian capital, including data from 2007 to 2010. Considering only E. coli (the most isolated agent), the resistance was 24.4% [11]. Reis AC et al., conducting another study including 1641 specimens also observed a high resistance to ciprofloxacin (18.4%) with a higher frequency of ciprofloxacin resistant E. coli (22.4%), when compared to other species [12]. Comparing two periods, Kiffer et al., demonstrated a trend of an increased resistance to quinolones from 2000 to 2003 [13]. Another alarming data was published in a study including 11.943 samples that also compared the susceptibility to antibiotics during two periods. There was a significant difference between the two periods studied (2005-2006; 2010-2011), with E. coli resistance to ciprofloxacin increasing from 7.1% to 15.1% [14]. Table 1 shows data about resistance pattern in Enterobacteriaceae of original studies mentioned above.
Table 1: Pattern of Enterobacteriaceae quinolone resistance.
|
Table 1: Pattern of Enterobacteriaceae quinolone resistance. |
||||
|
Author |
Period of study |
Country |
N species |
% Enterobacteriacae quinolone resistance |
|
Kresken M et al. |
1983-1990 |
Europe |
20,000 |
< 1 |
|
Aubert G et al. |
1986-1990 |
France |
17,902 |
3 – in general practice 10 – in hospitals |
|
Gales AC et al. |
1988 |
Latin America |
434 |
10.4 – 35.7 (hospital isolates) |
|
Andrade SS et al. |
2003 |
Latin America |
611 |
10.3 - 21.6 (community isolates) |
|
Cunha MA et al. |
2007-2010 |
Brazil |
1,082 |
24.4 – 30.2 |
|
Reis ACet al. |
2010-2014 |
Brazil |
1,641 |
18.4 (community isolates) |
|
Kiffer CR et al. |
2000-2003 |
Brazil |
37,261 |
4.2-38.7 (community isolates) |
|
Miranda EJet al. |
2005-2006 2010-2011 |
Brazil |
11,943 |
4.9-10.1 8.1-21.9 |
|
N = number |
||||
All these data alert to the overuse of quinolones and the increase of resistance around the world and in the Latin America. Although these surveillance resistance data are overestimated because usually, only specimens from people with complicated UTI tend to be submitted to culture, these trends are uncomfortable. Beyond this point, recently the U.S. Food and Drug Administration did a safety announcement alerting to serious side effects associated with fluoroquinolone antibacterial drugs and recommend that these drugs should be reserved for those who do not have alternative treatment options. We believe quinolones as empirical therapy, especially for patients with pyelonephritis and sepsis, must be considered carefully. In this situation, others drugs, like third generation cephalosporins and aminoglycosides are safer. Quinolone could be considered as an alternative especially considering the possibility of oral administration. Finally, nitrofurantoin and fosfomycin could be the first choice for the treatment of cystitis.
