toumei ../image GLOBAL Surveillance Data-
Updating the European S. pneumoniae Resistance Profile
Nina P. Brown, MS, Chris M. Pillar, PhD, Deborah C. Draghi, BS, Daniel F. Sahm, PhD, Clyde Thornsberry, PhD, Eurofins Medinet, Inc., Herdon, VA, USA

In order to maintain the optimal efficacy of antibacterial agents, it is extremely important that they are prescribed judiciously, thereby reducing the likelihood of resistance developing. A major feature of such evidence-based prescribing includes using knowledge about regional and international resistance patterns, as well as that relating to specific patient locations. Therefore, ongoing surveillance studies provide pivotal data on which the clinicians can base their therapeutic decision-making. Dr. Daniel F. Sahm, USA, outlined the current European situation in regard to antibacterial activity against the common respiratory pathogen S. pneumoniae, using data from the GLOBAL surveillance program.

When assessing the susceptibility profiles of pathogens, it is crucial to differentiate not only between results obtained from different nations, but also between specific sites. For example, it is important to know before prescribing an empiric agent whether the patient has presented from the community or is an outpatient or a hospitalized inpatient. In addition, sites within the hospital need to be further categorized into general medical wards, intensive care units (ICU) or long-term care facilities, as pathogens taken from these different areas can have marked differences in susceptibility profiles. This is because resistant organisms are much more likely to be found among hospitalized patients, in particular, those from specialist units such as intensive care. Dr. Daniel F. Sahm presented the latest European results investigating the activity of agents against the respiratory pathogen S. pneumoniae from a variety of different patient populations.
   The GLOBAL (Global Landscape On the Bactericidal Activity of Levofloxacin) 2007 surveillance evaluated S. pneumoniae isolates taken from 257 ICU, 684 inpatient, 168 long-term care, and 623 outpatient sites. Six European countries participated, namely, Belgium, France, Germany, Italy, Spain and the UK. All isolates were centrally tested by broth microdilution (CLSI M7-A7) and results interpreted according to CLSI M100-S18, apart from ciprofloxacin, where FDA breakpoints were applied. Multi-drug resistance (MDR) was defined as resistance to two of the following: penicillin, cefuroxime-axetil, azithromycin, trimethoprim-sulfamethoxazole and tetracycline.
   Results confirmed that penicillin-resistance (PEN-R) and MDR rates among S. pneumoniae varied according to the patient location, with PEN-R being highest in ICU (21.0%), followed by 12.0% in hospitalized patients, dropping to 6.9% in outpatients and 6.5% in long-term care patients. These results correlated with those relating to MDR rates, with the highest being in ICU (39.7%) followed by 30% in inpatients, 25.4% in outpatients and 21.4% in long-term care (Figure 1).

Figure 1. Rate of PEN-R and MDR rates among patient populations

   In regard to the fluoroquinolone activity against S. pneumoniae, Dr. Sahm reported that the MIC90s for levofloxacin remained stable at 1 mg/L regardless of the patient location or resistance phenotypes. In fact, the overall susceptibility of S. pneumoniae to levofloxacin remained at 98.8%, compared with the overall lower susceptibility rate for ciprofloxacin of 90.7% (Table).

Table. Antimicrobial susceptibility of all agents against all S. Pneumoniae isolates
Agent   % susceptible
Levofloxacin  98.8

   Susceptibility to specific antibacterial agents including ceftazidime, azithromycin, penicillin and trimethoprim-sulfamethoxazole was significantly influenced by the patient location. In fact, the MICs of β-lactams (penicillin, cefuroxime, ceftriaxone and amoxicillin-clavulanate) taken from ICU and inpatient isolates were at least 2- to 4-fold higher than those from outpatients and long-term care patients. In addition, the susceptibility of pathogens to azithromycin and trimethoprim-sulfamethoxazole was lowest among isolates from the ICU and inpatient populations. Further analysis of the results confirmed that more than 30% of S. pneumoniae isolates from these two locations had azithromycin MICs greater than 4 mg/L and over 16% had trimethoprim-sulfamethoxazole MICs greater than 4 mg/L.
   In sharp contrast to these results, more than 97% of all S. pneumoniae isolates remained susceptible to levofloxacin with an MIC90 of 1 mg/L, regardless of the patient location (Figure 2). Of particular note was the fact that levofloxacin maintained this greater than 97% activity against PEN-R and MDR S. pneumoniae isolates, confirming that it was the most potent of the eight antibacterial agents tested against S. pneumoniae (Table).

Figure 2. Percentage susceptibility of all agents tested against S. pneumoniae by patient location

   Investigating the activity of levofloxacin and another fluoroquinolone, ciprofloxacin, in more detail, revealed clear differences. While levofloxacin was active against 99.6% of S. pneumoniae from ICU, ciprofloxacin was only active against 89.1% of isolates from this site. In addition, levofloxacin was active against 98.4% of inpatient isolates compared with 90.9% for ciprofloxacin; levofloxacin was active against 98.9% of outpatient isolates compared with 92.0% for ciprofloxacin and, even more marked, levofloxacin was active against 99.4% of S. pneumoniae isolates from long-term care patients while ciprofloxacin was only active against 87.5% of these isolates.
   Therefore, Dr. Sahm concluded that in regard to S. pneumoniae PEN-R and MDR isolates were more likely to be identified in ICU and hospitalized patients. However, while most agents showed a clear trend to reduced activity with a move from outpatient to inpatient sites, this was not the case for the fluoroquinolones.
   These factors need to be carefully considered when embarking on empirical therapy for respiratory tract infections where S. pneumoniae is the likely pathogen. Clinicians can be confident that levofloxacin continues to exhibit excellent activity against both PEN-R and MDR S. pneumoniae, and has maintained its efficacy in all sites, including both outpatient and ICU.

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