Antimicrobial resistance among non-fermentative Gram-negative bacilli isolated from the respiratory tracts of Italian inpatients: a 3-year surveillance study by the Italian Epidemiological Survey

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Abstract

The Italian Epidemiological Survey evaluated antibiotic susceptibility of non-fermentative Gram-negative bacilli isolated from inpatient respiratory-tract specimens collected throughout Italy during 1997–1999. The minimal inhibitory concentrations of 14 antibiotics for 1474 Pseudomonas aeruginosa strains, 307 Stenotrophomonas maltophilia strains and 114 Acinetobacter baumannii strains were determined in 57 clinical microbiology laboratories by means of a standardised micro-dilution method. The most active drugs against P. aeruginosa isolates were meropenem (81% susceptible) and amikacin (80% susceptible). Imipenem and meropenem proved to be the only agents active against A. baumannii isolates, although 13 and 16%, respectively, of strains were resistant to these drugs. Trimethoprim-sulphamethoxazole (TMP-SMZ) showed activity only against S. maltophilia isolates (83% susceptible). A total of 185 multidrug-resistant P. aeruginosa isolates (resistant to piperacillin, ceftazidime, gentamicin, and imipenem) were found. Resistance rates and trends showed consistent regional variations, including sharp increases from 1997 to 1999 in imipenem resistance among P. aeruginosa isolates from central and southern Italy.

Introduction

Over the past few decades non-fermentative Gram-negative bacilli have emerged as important opportunistic pathogens. They are implicated in a significant number of infections, particularly in nosocomial pneumonia [1], [2], [3], [4]. Respiratory-tract colonisation and infection by resistant strains of Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia are facilitated by prolonged hospitalisation, increasing use of mechanical ventilation and empirical broad-spectrum antibiotic therapy.

From 14 to 30% of all cases of hospital-acquired pneumonia are caused by P. aeruginosa [3], [4]. Current therapeutic options for cases of this type include β-lactam agents (e.g., cephalosporins, carbapenems, penicillins and penicillin/β-lactamase inhibitors) alone or in combination with quinolones and aminoglycosides [1], [5], [6]. However, resistance to these agents, imipenem and the quinolones in particular, is increasing [7], [8]. The mechanisms underlying resistance to β-lactam agents include the production of β-lactamases, outer membrane permeability mutations and efflux pumps [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21]. The latter two mechanisms also play a role in resistance to aminoglycosides and quinolones [22], [23], [24]. Addition of mutations in DNA gyrase genes and the presence of aminoglycoside-modifying enzymes can lead to the emergence of multidrug-resistant strains of P. aeruginosa [15], [17], [25], [26], [27] and very few drugs (e.g., polymyxins) are effective against infections caused by these organisms [28], [29].

Acinetobacter species, primarily A. baumannii, account for 3–10% of all cases of pneumonia in nosocomial settings [2], [30], [31]. Unlike other nosocomial Gram-negative bacteria, these organisms are resistant to desiccation, and this factor might explain their propensity for causing extended epidemic outbreaks of infection [32]. Acinetobacter species are usually resistant to numerous antimicrobials [33]. In recent years, imipenem resistance among A. baumannii strains has been increasing in several hospitals [31], [34], [35], [36], [37], [38]. Infections caused by these organisms are difficult to treat since they generally respond only to the polymyxins and/or ampicillin/sulbactam [28].

S. maltophilia may be responsible for a wide spectrum of diseases. The respiratory tract, however, is the most common site of infection, and the incidence of these infections is on the increase (from 2.5% in 1998 to 4.1% in 1999) [30], [31]. S. maltophilia is intrinsically resistant to many commonly used antimicrobial agents and rapid selection of high-level multidrug-resistant isolates in clinical strains has been observed [39], [40]. S. maltophilia isolates produce a number of inducible enzymes, such as L1 (Bush group 3) zinc-dependent carbapenemase and L2 (Bush Group 2e) cephalosporinase, which hydrolyze important classes of β-lactams such as carbapenems and cephalosporins, respectively [41], [42]. Changes in outer membrane porin channels may also diminish the activity of several antimicrobials, including fluoroquinolones [22], [43], and an efflux mechanism responsible for acquired multidrug resistance in S. maltophilia has recently been discovered [44]. Trimethoprim-sulphamethoxazole (TMP-SMZ) is the drug of choice for treatment of S. maltophilia infections. Ticarcillin-clavulanic acid and fluoroquinolones are considered as potential therapeutic options. However, resistance to all of these drugs is increasing [31], [45], [46], [47], [48].

Treatment of hospital-acquired pneumonia caused by non-fermentative bacilli is difficult, and mortality is significant [49], [50]. The situation is further complicated by the increasing number of multidrug-resistant strains, which drastically reduce the chances for successful treatment, particularly in the initial empirical phase. In light of these problems, the need for accurate and ongoing surveillance of the phenomenon of [51], [52], [53] resistance becomes dear. This paper presents the results of the Italian Epidemiological Survey on antimicrobial resistance of P. aeruginosa, A. baumannii, and S. maltophilia isolates collected between January 1997 and December 1999.

Section snippets

Bacterial strains

During the study period, 57 Italian Microbiology laboratories (34 in northern regions, 11 in central regions and 12 in the southern region) were asked to collect at least 30 unique clinically significant isolates of non-fermentative Gram-negative bacilli from inpatient respiratory-tract specimens.

Susceptibility tests

For each isolate MICs for amikacin, aztreonam, cefepime, ceftazidime, ciprofloxacin, gentamicin, imipenem, meropenem, piperacillin, piperacillin/tazobactam, ticarcillin, ticarcillin-clavulanic acid,

Results

Table 1 summarizes the susceptibility profiles of 1895 non-fermentative Gram-negative isolates from respiratory specimens. Twenty-eight other isolates belonging to the Burkholderia cepacia complex were also grown but because of their limited number, they are not considered in the present report. While each of the isolates considered in this study was isolated from a different patient, their uniqueness was not verified by genotyping and therefore we cannot exclude the possibility of some degree

Discussion

P. aeruginosa, A. baumannii and S. maltophilia play key roles in nosocomial pneumonia, which carries the highest death toll of all hospital-acquired diseases [1], [5], [6], [49]. The increasing rates of resistance among these organisms are a cause for concern since the appropriateness of the initial empirical treatment of these infections appears to be a significant determinant of hospital mortality and clinical outcome in general [50], [52], [53]. The Italian Epidemiological Survey was

Acknowledgements

This work was supported by grant from by the Smith Kline Foundation. We thank Marian Kent for editorial assistance.

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