Are laboratory-based antibiograms reliable to guide the selection of empirical antimicrobial treatment in patients with hospital-acquired infections?

OBJECTIVES: Antibiograms are often taken into account to define a rational selection of an empirical antimicrobial therapy for treating patients with hospital-acquired infections. In this study, we performed a paired comparison between the antibiogram constructed with laboratory-based data and that formed with data subjected to prior clinical validation. METHODS: Between 2003 and 2005, the laboratory of microbiology printed in duplicate every individual susceptibility report corresponding to hospitalized patients and the copy was sent to the department of infection control. Every individual report was assessed in real time at the bedside of the patient by a multidisciplinary team for clinical significance and appropriateness of the specimen, as well as for the type, source and origin of the infection. Cumulative resistance rates were estimated in parallel at the laboratory with the whole data, and at the infection control department with data subjected to prior clinical validation. These rates were designated as 'laboratory-based' and 'clinically based', respectively. RESULTS: A total of 2305 individual susceptibility reports were assessed. Only 1429 (62.0%) were considered as clinically significant by the multidisciplinary team. Escherichia coli, Enterobacter cloacae, Citrobacter freundii group, Klebsiella species and Proteus mirabilis resistant to broad-spectrum cephalosporins, as well as methicillin-resistant Staphylococcus aureus, were significantly more frequent in the clinically based rates (P < or = 0.03). CONCLUSIONS: Laboratory-based data underestimate the frequency of several major resistant organisms in patients with hospital-acquired infection. Previous clinical validation of the individual susceptibility reports seems to be a suitable strategy to get more reliable data.

Replacement of broad-spectrum cephalosporins by piperacillin-tazobactam: impact on sustained high rates of bacterial resistance.

We have previously observed a significant reduction of ceftriaxone resistance in Proteus mirabilis associated with an increase in the use of cefepime, along with a decrease in the consumption of broad-spectrum cephalosporins (CEP). However, we did not observe such a reduction with Klebsiella pneumoniae. Therefore, we sought to determine whether replacement of CEP by piperacillin-tazobactam might be useful in reducing sustained high rates of CEP resistance by this organism. We used a 6-month "before and after model"; during the second (intervention) period, most prescriptions of CEP were changed to piperacillin-tazobactam at the pharmacy. No additional barrier precautions were undertaken. During intervention, consumption of ceftazidime decreased from 17.73 to 1.14 defined daily doses (DDD) per 1,000 patient-days (P < 0.0001), whereas that of piperacillin-tazobactam increased from 0 to 30.57 DDD per 1,000 patient-days (P < 0.0001). The levels of resistance to CEP by K. pneumoniae and P. mirabilis decreased from 68.4 and 57.9% to 37.5 and 29.4%, respectively (P < 0.05). We conclude that replacement of ceftazidime by piperacillin-tazobactam might be a suitable strategy to decrease endemic CEP resistance by K. pneumoniae and P. mirabilis, even where there are high bacterial resistance rates and irrespective of any additional precautions for controlling nosocomial infection.

Argentinean collaborative multicenter study on the in vitro comparative activity of piperacillin-tazobactam against selected bacterial isolates recovered from hospitalized patients.

The in vitro activity of piperacillin-tazobactam and several antibacterial drugs commonly used in Argentinean hospitals for the treatment of severe infections was determined against selected but consecutively isolated strains from clinical specimens recovered from hospitalized patients at 17 different hospitals from 9 Argentinean cities from different geographic areas during the period November 2001-March 2002. Out of 418 Enterobacteriaceae included in the Study 84% were susceptible to piperacillin-tazobactam. ESBLs putative producers were isolated at an extremely high rate since among those isolates obtained from patients with hospital acquired infections 56% of Klebsiella pneumoniae, 32% of Proteus mirabilis and 25% Escherichia coli were phenotypically considered as ESBLs producers Notably P.mirabilis is not considered by for screening for ESBL producers. ESBLs producers were 100% susceptible to imipenem and 70% were susceptible to piperacillin-tazobactam whereas more than 50% were resistant to levofloxacin. The isolates considered as amp C beta lactamase putative producers showed 99% susceptibility to carbapenems while 26.7% were resistant to piperacillin-tazobactam and 38.4% to levofloxacin. Noteworthy only 4% of the Enterobacteriaceae isolates were resistant to amikacin. Piperacillin-tazobactam was the most active agent against Pseudomonas aeruginosa isolates (MIC(90): 128 microg/ml; 78% susceptibility) but showed poor activity against Acinetobacter spp (MIC(90):>256 microg/ml; 21.7% susceptibility). Only 41.7% Acinetobacter spp isolates were susceptible to ampicillin-sulbactam. Piperacillin-tazobactam inhibited 100% of Haemophilus influenzae isolates (MIC(90) < 0.25 microg/ml) but only 16.6% of them were ampicillin resistant. The activity of piperacillin-tazobactam against oxacillin susceptible Staphylococcus aureus or coagulase negative staphylococci was excellent (MIC(90) 2 microg/ml; 100% susceptibility). Out of 150 enterococci 12 isolates (8%) were identified as E.faecium and only three isolates (2%), 2 E.faecium and 1 E.faecalis were vancomycin resistant. All the enterococci isolates were susceptible to linezolid. Piperacillin-tazobactam showed excellent activity (MIC(90) 2 microg/ml; 92% susceptibility). Regarding pneumococci all the isolates showed MICs of 16 microg/ml for piperacillin-tazobactam. Among 34 viridans group streptococci only 67% were penicillin susceptible and 85.2% ceftriaxone susceptible whereas piperacillin-tazobactam was very active (MIC(90) 4 microg/ml).Piperacillin-tazobactam is therefore a very interesting antibacterial drug to be used, preferably in combination (IE: amikacin-vancomycin) for the empiric treatment of severe infections occurring in hospitalized patients in Argentina. Caution must be taken for infections due to ESBL producers considering that the inoculum effect MICs can affect MIC values.

A hospitalwide intervention program to optimize the quality of antibiotic use: impact on prescribing practice, antibiotic consumption, cost savings, and bacterial resistance.

Several findings from Argentina provide compelling evidence of the need for more rational use of antimicrobial agents. Thus, a multidisciplinary antimicrobial treatment committee for the development of a hospital-wide intervention program was formed to optimize the quality of antibiotic use in hospitals. Four successive steps were developed during 6-month periods: baseline data collection, introduction of a prescription form, education, and prescribing control. Sustained reduction of drug consumption was shown during the study (R2=0.6885; P=.01). Total cost savings was 913,236 US dollars. To estimate the consumption of cefepime and aminopenicillin-sulbactam in relation to that of the third-generation cephalosporins, 2 indices were calculated: Icfp and Iams, respectively. Decreasing resistance to ceftriaxone by Proteus mirabilis and Enterobacter cloacae proved to be associated with increasing Icfp. Decreasing rates of methicillin-resistant Staphylococcus aureus were related to increasing Iams. The present study indicates that a systematic program performed by a multidisciplinary team is a cost-effective strategy for optimizing antibiotic prescribing.