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Antimicrobial Agents and Chemotherapy, April 1999, p. 981-982, Vol. 43, No. 4
Servicio de Microbiología y
Enfermedades Infecciosas-VIH, Hospital General Universitario
"Gregorio Marañón," 28007 Madrid, Spain
Received 10 November 1998/Returned for modification 17 December
1998/Accepted 5 February 1999
We carried out a nationwide study with all of the isolates of
Pseudomonas aeruginosa collected in a week in 136 hospitals in Spain. The data on 1,014 isolates included resistance to the following antimicrobials: piperacillin-tazobactam, 7%; meropenem, 8%;
amikacin, 9%; tobramycin, 10%; piperacillin, 10%; ticarcillin, 13%;
imipenem, 14%; ceftazidime, 15%; cefepime, 17%; ciprofloxacin, 23%;
aztreonam, 23%; ofloxacin, 30%; gentamicin, 31%. The most frequent
serotypes were O:1 (25.1%), O:4 (21.6%), and O:11 (11.3%).
Pseudomonas aeruginosa is
a nosocomial pathogen responsible for infections in immunocompromised
hosts. Most studies report the resistance of P. aeruginosa
to antimicrobials in special units and special types of patients.
However, data regarding the antimicrobial susceptibility of P. aeruginosa without a priori selection are scarce.
The changing and easy acquisition of resistance in P. aeruginosa requires rapid surveillance procedures to represent the
whole reality of the situation at a given point in time. Here we report a recent national point prevalence study (1998) of all of the P. aeruginosa isolates collected during a whole week in 136 randomly selected hospitals that are representative of all of the types and
sizes of public hospitals found throughout Spain.
All isolates were sent to the same reference laboratory for
reidentification and susceptibility testing without duplication of
strains from the same patient and sample. All isolates were accompanied
by a uniform protocol which included the characteristics of the
hospital of origin, the number of beds, the ward, the sites of
isolation, and acquisition from outpatients or inpatients. Identities
and MICs were determined by using MicroScan Neg Combo 1S panels
(MicroScan, Baxter Diagnostics, Inc., West Sacramento, Calif.) and
following the manufacturer's guidelines. Those isolates whose
identification was inconclusive were subjected to reidentification by
standard procedures (4). The antimicrobials and
concentrations (micrograms per milliliter) tested were as follows:
ticarcillin and piperacillin 16 and 64; piperacillin-tazobactam,
16/4 and 64/4; ceftazidime, cefepime, and aztreonam, 1 to 2 and 8 to
16); imipenem, 1 to 8; meropenem, 4 to 8, ciprofloxacin, 0.12 and 1 to
2; ofloxacin, 0.5 and 2 to 4; gentamicin and tobramycin, 4 to 8;
amikacin, 8 to 16. Each panel was inoculated with an appropriate dilution of an exponential phase culture of a microorganism. Readings were performed after overnight incubation at 35°C. Escherichia coli ATCC 25922 and P. aeruginosa ATCC 27853 were used
daily as control strains. Breakpoints were applied following National
Committee for Clinical Laboratory Standards (NCCLS) recommendations
(6). When resistance rates were calculated, MIC in both the
intermediate and resistant ranges, as defined by the NCCLS, were
considered as nonsusceptible in this study. Serotyping was performed by
a slide agglutination method using 17 monovalent P. aeruginosa antisera from the international antigenic typing
scheme (7). Susceptibility data were compared by using
a chi-square test.
A total of 1,014 isolates were studied. Data regarding antimicrobial
resistance are summarized in Table 1. The
most active antimicrobials (resistance in
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Copyright © 1999, American Society for Microbiology. All rights reserved.
Pseudomonas aeruginosa: a Survey of
Resistance in 136 Hospitals in Spain
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15% of all isolates) were
amikacin, ceftazidime, imipenem, meropenem, piperacillin-tazobactam,
ticarcillin, and tobramycin. By contrast, gentamicin and ofloxacin were
the least active antimicrobial agents, with percentages of resistance of 31 and 30%, respectively. A large proportion of isolates (30.5%) were obtained from outpatients and the highest resistance was observed,
in general, among the nosocomial isolates (although the difference was
only statistically significant for ceftazidime and carbapenems). Among
isolates from outpatients (24.5%), resistance to quinolones was
significantly higher than that to other antimicrobial agents
(P < 0.05). For outpatient isolates, urine was the
most common site of isolation (31%), significantly more common than lower respiratory tract (P < 0.05). In contrast for
strains from inpatients, lower respiratory tract was the most common
site of isolation, significantly more common than urine (P < 0.05). We found significant differences (P < 0.05) regarding resistance to the following antimicrobials under
the following circumstances: isolates from intensive care units were
more resistant to aztreonam, cefepime, ceftazidime, imipenem,
ticarcillin, piperacillin, and piperacillin-tazobactam than those
from other clinical settings; isolates from inpatients were
significantly most often resistant to ceftazidime, imipenem, and
meropenem; and isolates from outpatients were more often resistant to
ciprofloxacin than were nosocomial isolates.
TABLE 1.
In vitro activities of antimicrobial agents against
P. aeruginosa
P. aeruginosa was isolated in polymicrobial culture from
30% of the specimens (40% of those were from wounds or abscesses). Table 2 summarizes the cross-resistance
of P. aeruginosa isolates to antimicrobial agents. The
majority of meropenem-resistant isolates were also resistant to
imipenem, and about one-half of these isolates and two-thirds of the
imipenem-resistant isolates were susceptible to ceftazidime,
piperacillin-tazobactam, and ciprofloxacin. About one half of the
ceftazidime-resistant isolates (MIC,
16 µg/ml) were susceptible to
piperacillin-tazobactam (MIC,
64/4 µg/ml), and around 70% were
susceptible to imipenem and meropenem. All amikacin-nonsusceptible
isolates (MIC, >16 µg/ml) were also resistant to gentamicin, but
surprisingly, 44% were susceptible to tobramycin (MIC,
4 µg/ml).
Seventy percent of the gentamicin-resistant isolates were susceptible
to tobramycin and amikacin. More than two-thirds of the
ciprofloxacin-resistant isolates were susceptible to ceftazidime, carbapenems, piperacillin-tazobactam, tobramycin, and amikacin.
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The serotypes found were O:1 (25.1%), O:4 (21.6%), O:11 (11.3%), O:2 (8.3%), O:3 (7.1%), O:8 (6%), O:9 (3.2%), O:12 (2.8%), and others (14.6%).
Our study shows an inexpensive method to assess the situation of P. aeruginosa in a very large population without selecting types of patients and/or special situations. In a recent study, P. aeruginosa was the fourth most common nosocomial pathogen in the United States (5). To our surprise, in our study, a high percentage of P. aeruginosa isolates were obtained from outpatients and 24.5% of them were resistant to quinolones. This study was not specifically designed to address the definition of community-acquired infections according to Centers for Disease Control and Prevention criteria but points against P. aeruginosa as a potential pathogen in patients outside the hospital. The low percentage of susceptibility to ciprofloxacin may reflect the ubiquitous use of quinolones in the community.
This study demonstrates that
-lactams, despite having been in use
for a longer time, have higher in vitro activity than quinolones. Recent studies in France and Italy (1, 2) showed similar results, although resistance percentages are lower in Spain, especially for ciprofloxacin (higher than 30% in France and Italy).
Cross-resistance data indicate that a high number of isolates probably
have resistance due to a combination of multiple unrelated resistance mechanisms.
The distribution of serotypes in Spain may have changed in recent years. A previous report obtained from 1980 to 1991 shows a different distribution (10). The main changes are the increase of serotypes O:4 and O:1 (from 8.7 to 14.4% and from 20.6 to 25.1%, respectively). Another important serotype, O:11, which is related to outbreaks and multi-drug resistance (3, 9), also accounts for an important percentage of the isolates found in our country, while serotype O:12, well known by its spread in all of Europe (8), accounts for a low percentage of the isolates found in Spain.
This study shows that periodical surveillance studies of this type, when resources are limited, provide very useful data on the overall situation in a country.
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FOOTNOTES |
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* Corresponding author. Mailing address: Servicio de Microbiología y Enfermedades Infecciosas-VIH, Hospital General Universitario "Gregorio Marañón," Dr. Esquerdo 46, 28007 Madrid, Spain. Phone: 91-5868453. Fax: 91-3721721. E-mail: ebouza{at}microb.net.
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