toumei ../image Global Surveillance Studies: Ensuring Optimum RTI and UTI Therapeutic Strategies
Nina P. Brown, MS, Clyde Thornsberry, PhD, Daniel F. Sahm, PhD
Eurofins Medinet, Inc., Chantilly, VA, USA

Concerns over resistance continue to be voiced throughout the infectious disease community. However, while there has been an escalation of resistance to many commonly used antimicrobials, others, such as levofloxacin, have maintained their efficacy. The following reports on two major surveillance studies with 2010 susceptibility data provides physicians with the most up-to-date evidence on which they can base optimal therapeutic regimens.

Streptococcus pneumoniae and Haemophilus influenzae remain two of the most important causative pathogens responsible for respiratory tract infections (RTI) worldwide. To ensure optimal empiric treatment of RTI, a number of surveillance studies have been initiated with one of the major international studies, the ongoing GLOBAL (Global Landscape On the Bactericidal Activity of Levofloxacin) program. Dr. Brown, Dr. Thornsberry and Dr. Sahm reported results incorporating data from 2006 to February 2010, including 2,153 S. pneumoniae and 2,095 H. influenzae isolates from six European countries (Belgium, France, Germany, Italy, Spain and the UK).
   In addition, they evaluated susceptibility profiles in specific patient subgroups, looking at how patient age, location (outpatient, inpatient and intensive care unit [ICU]) as well as country of origin impact on results. Stringent measures were used to ensure standardized testing with all isolates centrally tested by broth microdilution according to CLSI standards. To be defined as multi-drug resistant (MDR), isolates had to be resistant to two or more of the following agents: penicillin, cefuroxime, azithromycin, trimethoprim-sulfamethoxazole (TMP-SMX) and tetracycline.
   Results confirmed that levofloxacin was the most potent anti-pneumococcal agent, with 98.7% of isolates remaining susceptible to this fluoroquinolone. In contrast, azithromycin susceptibility was lowest at 68.0% and penicillin susceptibility was only 80.0% (Table 1).

Table 1.Antimicrobial susceptibility of all agents tested against S. pneumoniae

   Of even more clinical importance was the finding that levofloxacin remained effective in treating 97.2% of MDR pneumococcal isolates. In contrast, the efficacy of the other antimicrobials dropped dramatically when treating penicillin-resistant S. pneumoniae or MDR pneumococcal isolates, with azithromycin, amoxicillin-clavulanate, cefuroxime-axetil, penicillin, tetracycline and TMP-SMX effective against only 11.0%, 87.3%, 43.5%, 40.0%, 21.9% and 39.7% of MDR isolates, respectively.
   Investigation of specific patient subgroups revealed that penicillin-resistant and MDR pneumococcal isolates were more common in pediatric patients as well as those in ICU. It was noted that levofloxacin resistance among S. pneumoniae was rare, and only observed in 1.3% of adult or 1.4% of elderly patients (Figure).

Figure. S. pneumoniae resistance rates to commonly used RTI agents according to patient age
MDR = multi-drug resistant.

   GLOBAL results also updated the H. influenzae susceptibility profile. Researchers reported that isolates were 100% susceptible to levofloxacin and amoxicillin-clavulanate, even including the β-lactamase producing strains. TMP-SMX was the least effective agent tested against H. influenzae with only 78.7% of isolates susceptible.
   The researchers concluded that continued surveillance is necessary to provide data on variations in resistance patterns that need to be considered when selecting empiric treatment of RTI. Based on these latest results, levofloxacin remains an effective agent in managing the most common RTI pathogens, including MDR strains.
   In addition to RTI, urinary tract infections (UTI) are among the most common problems seen by physicians. A European surveillance report looked at the activity of common UTI agents and the impact of patient age (pediatric patients defined as ≤17 years, and elderly ≥65 years) and location (outpatient, inpatient and ICU) on activity. This report also presented by Dr. Brown, Dr. Sahm and colleagues noted that there is increasing concern about resistance among Enterobacteriaceae spp., with isolates now presenting with extended-spectrum β-lactamase (ESBL) production or multi-drug resistance. As part of the GLOBAL survey, 2,056 urinary isolates were collected from six European countries (906 Escherichia coli, 388 Klebsiella pneumoniae, 448 Proteus spp., 314 other Enterobacteriaceae spp.). The following agents were tested for activity against the isolates: levofloxacin, ciprofloxacin, amoxicillin-clavulanate and TMP-SMX. An isolate was defined as MDR if it was resistant to three or more separate classes of agents.
   The survey found that overall Enterobacteriaceae resistance was highest to TMP-SMX at 34.6%. Among the two fluoroquinolones tested, resistance was higher to ciprofloxacin than levofloxacin for all Enterobacteriaceae spp. (Table 2).

Table 2. Resistance rates for selected antimicrobials for Enterobacteriaceae
Agent    E. coli    K. pneumoniae    All Enterobacteriaceae
Levofloxacin  22.5  9.8  13.9
E. coli = Escherichia coli, K. pneumoniae = Klebsiella pneumoniae.

   More detailed analysis also demonstrated that 4.5% of E. coli and 11.9% of K. pneumoniae were ESBL producers. In addition, ESBL producers were more commonly identified among inpatient groups, particularly those admitted to ICU. Regarding MDR rates, 3.6% of all Enterobacteriaceae were defined as MDR, ranging from 2 to 4% across the subpopulations. Therefore, researchers concluded that, in general, Enterobacteriaceae resistance tended to increase with increasing age and was highest among ICU patients and these factors need to be considered when treating UTI empirically.

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