Comparative in vitro antimicrobial activity of tigecycline, a new glycylcycline compound, in freshly prepared medium and quality control

The in vitro spectra of activity of tigecycline and tetracycline were determined for 2,490 bacterial isolates representing 50 different species or phenotypic groups. All isolates were tested simultaneously by broth microdilution using freshly prepared Mueller-Hinton broth and by disk diffusion. Portions of these data were submitted to the Food and Drug Administration (FDA) in support of the sponsor's application for new drug approval. In a separate study, MIC and disk diffusion quality control ranges were determined. The tigecycline MICs at which 50%/90% of bacteria were inhibited were (in microg/ml) as follows: for Streptococcus spp., 0.06/0.12; for Moraxella catarrhalis, 0.06/0.12; for Staphylococcus spp., 0.12/0.25; for Enterococcus spp., 0.12/0.25; for Listeria monocytogenes, 0.12/0.12; for Neisseria meningitidis, 0.12/0.25; for Haemophilus spp., 0.25/0.5; for Enterobacteriaceae, 0.05/2.0; for non-Enterobacteriaceae, 0.5/8.0. Tigecycline was consistently more potent than tetracycline against all species studied. The data from this study confirm the FDA-approved MIC and disk diffusion breakpoints for tigecycline for Streptococcus spp. other than Streptococcus pneumoniae, enterococci, and Enterobacteriaceae. Provisional breakpoints for Haemophilus spp. and S. pneumoniae are proposed based on the data from this study. The following MIC and/or disk diffusion quality control ranges are proposed: Staphylococcus aureus ATCC 29213, 0.03 to 0.25 microg/ml; S. aureus ATCC 25923, 20 to 25 mm; Escherichia coli ATCC 25922, 0.03 to 0.25 microg/ml and 20 to 27 mm; Pseudomonas aeruginosa ATCC 27853, 9 to 13 mm, Enterococcus faecalis ATCC 29212, 0.03 to 0.12 microg/ml; S. pneumoniae ATCC 49619, 0.015 to 0.12 microg/ml and 23 to 29 mm; Haemophilus influenzae ATCC 49247, 0.06 to 0.5 microg/ml and 23 to 31 mm; and Neisseria gonorrhoeae ATCC 49226, 30 to 40 mm.     

Evaluation of the Hyplex BloodScreen Multiplex PCR-Enzyme-linked immunosorbent assay system for direct identification of gram-positive cocci and gram-negative bacilli from positive blood cultures

We evaluated the Hyplex BloodScreen PCR-enzyme-linked immunosorbent assay (ELISA) system (BAG, Lich, Germany), a new diagnostic test for the direct identification of gram-negative bacilli and gram-positive cocci from positive blood cultures, with 482 positive BACTEC 9240 blood culture bottles. The test involves amplification of the bacterial DNA by multiplex PCR and subsequent hybridization of the PCR product to specific oligonucleotide probes in an ELISA-based format. The available probes allow the separate detection of Escherichia coli, Pseudomonas aeruginosa, Enterobacter aerogenes, Klebsiella spp., Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis/Enterococcus faecium, Streptococcus pyogenes, and Streptococcus pneumoniae and the staphylococcal mecA gene. The Hyplex BloodScreen test showed an overall sensitivity of 100% for the identification of gram-negative bacilli and 96.6 to 100% for the identification of gram-positive cocci (S. aureus, 100%; S. epidermidis, 97.2%; Enterococcus faecalis/Enterococcus faecium, 96.6%; and Streptococcus pneumoniae, 100%). The specificities of the test modules ranged from 92.5 to 100% for gram-negative bacilli and 97.7 to 100% for gram-positive cocci (Escherichia coli, 92.5%; Pseudomonas aeruginosa, 98.5%; Klebsiella spp., 100%; Enterobacter aerogenes, 100%; S. aureus, 100%, S. epidermidis, 97.7%; Enterococcus faecalis/Enterococcus faecium, 99.6%; Streptococcus pyogenes, 100%; and Streptococcus pneumoniae, 99.3%). The result of the mecA gene detection module correlated with the result of the phenotypic oxacillin resistance testing in all 38 isolates of Staphylococcus aureus investigated. In conclusion, the Hyplex BloodScreen PCR-ELISA system is well suited for the direct and specific identification of the most common pathogenic bacteria and the direct detection of the mecA gene of Staphylococcus aureus in positive blood cultures.     

Community-acquired pneumonia--from medical technologist

The main causative microorganisms of Community-acquired pneumonia are Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus. Especially the causative microorganisms affecting whole body basic disease, persons of advanced age, and alcoholic patients are Moraxella catarrhalis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Candida spp., Cryptococcus spp., Aspergillus spp., Pneumocystis carinii and anaerobic bacteria. Other microorganisms involved in epidemic disease, action condition (travel around hot springs etc.) and pet breeding environments are Mycoplasma pneumoniae, Legionella pnumophila, Chlamydia spp., respiratory syncytial virus, influenza virus, and adeno virus. We suggest methods of advancing the microscopic and microbiological examination and report, and quickly obtaining clinical information and extracting the clinical specimen. We also describe the inspection method for a case "Legionella pneumonia" that was discussed during this symposium.     

Rapid identification of Staphylococcus aureus and Streptococcus pneumoniae from blood cultures.

Simultaneous application of the lysostaphin sensitivity test for identification of Staphylococcus aureus and the deoxycholate test for the identification of Streptococcus pneumoniae was evaluated for reliability in rapid identification (1 h) of these organisms from blood cultures by using BACTEC 6B and 7C bottles. The procedure was applied to 127 cultures, 74 lysostaphin tests and 53 deoxycholate tests. Lysostaphin-tested organisms included 23 S. aureus, 40 Staphylococcus epidermidis, 1 Listeria sp., 1 Peptococcus sp., 2 Micrococcus sp., 2 diphtheroids, and 5 mixed cultures. Deoxycholate-tested organisms included 14 S. pneumoniae, 32 Streptococcus spp. (not S. pneumoniae), 1 Listeria sp., 1 Peptococcus sp., 2 diphtheroids, and 3 mixed cultures. Analysis of the data revealed positive and negative predictive values of 95.8 and 94%, respectively, for the lysostaphin test and 100 and 97.4%, respectively, for the deoxycholate test. The combined tests provide rapid reliable identification or elimination of S. aureus and S. pneumoniae in blood cultures.     

Controlled clinical comparison of two lysis-based blood culture systems, isolator and Septi-Chek Release, for detection of bloodstream infections.

A controlled clinical comparison was made of the Isolator (Wampole Laboratories, Cranbury, N.J.) and the Septi-Chek Release bottle (Roche Diagnostics, Nutley, N.J.). From 6,345 blood culture sets fulfilling minimum criteria for volume of blood cultured, 840 strains were isolated, of which only 691 (82%) were considered to be representative of bloodstream infection according to Centers for Disease Control definitions. Statistically significant differences were found between the systems for the following organisms, which were all detected more frequently in the Isolator system: Staphylococcus aureus (P = 0.0001), Alcaligenes xylosoxidans (P = 0.008), Klebsiella pneumoniae (P = 0.05), Salmonella spp. (P = 0.03), and Candida albicans (P = 0.02). The Septi-Chek Release system required a longer period of time than the Isolator system for detection of the following organisms:S. aureus (P = 0.0001), Enterococcus spp. (P = 0.0001), Enterobacter cloacae (P = 0.03), Escherichia coli (P = 0.0001), Klebsiella oxytoca (P = 0.03), K. pneumoniae (P = 0.02), Pseudomonas aeruginosa (P = 0.002), and C. albicans (P = 0.005). There were 430 episodes of bloodstream infections identified in the study; of these episodes, only those due to S. aureus were detected significantly more frequently (P = 0.0001) by the Isolator system than by the Septi-Chek Release system. However, episodes of bloodstream infections due to S. aureus, Staphylococcus epidermidis, Enterococcus spp., and E. coli were detected significantly faster by the Isolator system.     

In vitro activity of quinupristin/dalfopristin against selected bacterial pathogens isolated in Italy

Objectives: To evaluate the activity of quinupristin/dalfopristin, a new injectable streptogramin, against 732 clinical strains recently isolated in Italy.
Methods: Susceptibility tests were performed according to NCCLS-guided MIC methodology. Pathogens included in the evaluation included 108 Staphylococcus aureus isolates, 124 coagulase-negative staphylococcal isolates, 158 Streptococcus pyogenes isolates, 30 Streptococcus agalactiae isolates, 30 β-hemolytic streptococcal isolates, 18 Streptococcus sanguis isolates, 80 Streptococcus pneumoniae isolates, 69 Enterococcal isolates, 40 Haemophilus influenzae isolates, 30 Moraxella catarrhalis isolates and, finally, 30 Gram-positive and 25 Gram-negative anaerobes.
Results: Quinupristin/dalfopristin inhibited Staphylococcus aureus and other Staphylococcus spp., irrespective of their oxacillin or erythromycin resistance phenotypes. Similarly, streptococci were fully inhibited by quinupristin/dalfopristin. Enterococcus faecalis was not included in the spectrum of this streptogramin, while isolates of Enterococcus faecium were inhibited by the new compound. Respiratory pathogens such as H. influenzae and M. catarrhalis were inhibited by quinupristin/dalfopristin as well as all Gram-negative anaerobes tested.
Conclusions: These findings suggest a putative role for quinupristin/dalfopristin in the empirical treatment of severe nosocomial and community-acquired infections caused by pathogens often displaying resistance to multiple antibiotics. This drug may provide an alternative to glycopeptide compounds.     

Comparative in vitro activity of the new oral penem ALP-201 against aerobic and anaerobic bacteria

The in vitro activity of the new penem derivative ALP-201 against 226 aerobic and 350 anaerobic clinical bacterial isolates was determined using agar dilution techniques. For comparison amoxicillin, cefaclor, ceftazidime, doxycycline, erythromycin, imipenem and trimethoprim/sulfamethoxazole were also tested with aerobic bacteria, and cefoxitin, chloramphenicol, clindamycin, imipenem, metronidazole and piperacillin with anaerobic bacteria. ALP-201 was found to be highly active againstEscherichia coli, Klebsiella spp.,Enterobacter spp.,Haemophilus influenzae, Branhamella catarrhalis, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, anaerobic cocci,Propionibacterium acnes, Clostridium perfringens, Bacteroides fragilis, Bacteroides spp. and fusobacteria.Pseudomonas aeruginosa andClostridium difficile were resistant to ALP-201. When tested against aerobic bacteria using a high inoculum or using the broth dilution technique, the activity of ALP-201 showed little dependence on inoculum size and the bactericidal activity was similar to the inhibitory activity. Further investigations are warranted with ALP-201, which is absorbed from the gastrointestinal tract after oral administration.     

Antimicrobial activity of dalbavancin tested against Gram-positive clinical isolates from Latin American medical centres

The activity of dalbavancin, a new semi-synthetic lipoglycopeptide antibiotic, was evaluated in comparison with other antibacterial agents against 1229 Gram-positive organisms collected from medical centres in Latin America. Dalbavancin was the most potent compound tested against isolates of Staphylococcus aureus (MIC(50), 0.06 mg/L) and coagulase-negative staphylococci (MIC(50), 0.03 mg/L), independently of methicillin susceptibility. Dalbavancin inhibited all Streptococcus pneumoniae isolates at /= 8 mg/L. Dalbavancin exhibited excellent activity against isolates of Corynebacterium spp. and Listeria spp. Dalbavancin may provide an important therapeutic option for Gram-positive infections, excluding those caused by enterococci with VanA-type resistance.     

In-vitro activities of cefamandole and cephalothin against 1,881 clinical isolates. A multi-center study

By use of an agardilution technic, 1,881 clinical isolates were tested against cefamandole and cephalothin. The isolates represented 18 genera, recovered in five geographically separate centers within the United States. The majority of strains were susceptible (MICs less than or equal to 8 micrograms/ml) to both drugs. Cefamandole showed greater activity against most of the bacterial pathogens. Enterococci, Serratia spp., and Acinetobacter spp. were resistant to both drugs. Cephalothin was more active against Staphylococcus aureus, and both cephalosporins were relatively inactive against methicillin-resistant strains of S. aureus. Enterobacter spp. and indole-positive Proteus spp. were susceptible to cefamandole but resistant to cephalothin.     

Introduction: Evolving needs in respiratory tract infections

Two issues that have become clinically relevant to the treatment of pneumonia over the past few years are the development of antibiotic resistance among respiratory pathogens and the increasing importance of the atypical respiratory pathogens— Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella spp.
Resistance has become an important issue in Streptococcus pneumoniae , methicillin-resistant Staphylococcus aureus and Gram-negative rods. The ways by which bacteria become resistant to antibiotics include production of antibiotic-modifying enzymes, reduced access to target sites, efflux of antibiotic, change in the bacterial target site and the bypassing of inhibited pathways. In Streptococcus pneumoniae that are penicillin resistant, the mechanism is through alteration of the target site for penicillins (penicillin-binding proteins) and this may also confer resistance to some cephalosporins. Multidrug resistance has also been reported in some strains of pneumococci. Of particular concern is resistance to macrolides mediated by the ermAM gene, which also confers resistance to lincosamides and streptogramin-B drugs. In Staphylococcus aureus , resistance to virtually all β-lactam drugs is mediated by acquisition of the mecA gene, which codes for the drug-resistant β-lactam target PBP2a.
Antimicrobials are now needed that have enhanced activity against aerobic Gram-negative rods, atypical respiratory pathogens and Gram-positive cocci.     

Antibacterial activity of microbicidal cationic proteins 1 and 2, natural peptide antibiotics of rabbit lung macrophages.

Microbicidal cationic proteins 1 and 2, peptides derived from rabbit lung macrophages, were tested for bactericidal activity against various bacterial species. Both were highly active against diverse gram-positive and gram-negative organisms under conditions of near-neutral pH (between 7 and 8) and relatively low ionic strength. Susceptible species included Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Listeria monocytogenes, Pseudomonas aeruginosa, Klebsiella pneumoniae, Haemophilus influenzae, Escherichia coli, and Serratia marcescens. Streptococcus agalactiae, type 1A, was less susceptible than the aforementioned organisms or S. agalactiae, type 3. Bordetella bronchiseptica, a common commensal and pathogen of the rabbit respiratory tract, was completely resistant to both peptides.     

Microbiological profile of telithromycin, the first ketolide antimicrobial

Telithromycin, the first of the ketolide antimicrobials, has been specifically designed to provide potent activity against common and atypical/intracellular or cell-associated respiratory pathogens, including those that are resistant to β-lactams and/or macrolide–lincosamide–streptogramin_B (MLS_B) antimicrobials. Against Gram-positive cocci, telithromycin possesses more potent activity in vitro and in vivo than the macrolides clarithromycin and azithromycin. It retains its activity against erm -(MLS_B) or mef -mediated macrolide-resistant Streptococcus pneumoniae and Streptococcus pyogenes and against Staphylococcus aureus resistant to macrolides through inducible MLS_B mechanisms. Telithromycin also possesses high activity against the Gram-negative pathogens Haemophilus influenzae and Moraxella catarrhalis , regardless of β-lactamase production. In vitro , it shows similar activity to azithromycin against H. influenzae , while in vivo its activity against H. influenzae is higher than that of azithromycin. Telithromycin's spectrum of activity also extends to the atypical, intracellular and cell-associated pathogens Legionella pneumophila , Mycoplasma pneumoniae and Chlamydia pneumoniae . In vitro , telithromycin does not induce MLS_B resistance and it shows low potential to select for resistance or cross-resistance to other antimicrobials. These characteristics indicate that telithromycin will have an important clinical role in the empirical treatment of community-acquired respiratory tract infections.     

Postantibiotic effect of the penem FCE 22101 against selected gram-positive and gram-negative bacteria in vitro and in vivo by the use of a tissue cage model in rabbits

Isolates of Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae and Klebsiella pneumoniae were tested for their bactericidal activity and postantibiotic effect (PAE) with the new penem FCE 22101. The tissue cage model in rabbits was used to study PAE in vivo. The bactericidal activity against all four species was shown to be in the range of 0.05-4.0 mg/l. A 99.9% killing effect at MBC concentrations was reached within 2 hours with S. pneumoniae and K. pneumoniae and within 6-8 hours with S. aureus and H. influenzae. After in vitro exposure by FCE 22101 a PAE in vitro and in vivo was obtained against S. aureus, S. pneumoniae and H. influenzae strains but no PAE could be demonstrated against K. pneumoniae. FCE 22101 showed a good bactericidal activity and PAE against the strains investigated, except for K. pneumoniae.     

Molecular probes for diagnosis of clinically relevant bacterial infections in blood cultures

Broad-range real-time PCR and sequencing of the 16S rRNA gene region is a widely known method for the detection and identification of bacteria in clinical samples. However, because of the need for sequencing, such identification of bacteria is time-consuming. The aim of our study was to develop a more rapid 16S real-time PCR-based identification assay using species- or genus-specific probes. The Gram-negative bacteria were divided into Pseudomonas species, Pseudomonas aeruginosa, Escherichia coli, and other Gram-negative species. Within the Gram-positive species, probes were designed for Staphylococcus species, Staphylococcus aureus, Enterococcus species, Streptococcus species, and Streptococcus pneumoniae. The assay also included a universal probe within the 16S rRNA gene region for the detection of all bacterial DNA. The assay was evaluated with a collection of 248 blood cultures. In this study, the universal probe and the probes targeting Pseudomonas spp., P. aeruginosa, E. coli, Streptococcus spp., S. pneumoniae, Enterococcus spp., and Staphylococcus spp. all had a sensitivity and specificity of 100%. The probe specific for S. aureus showed eight discrepancies, resulting in a sensitivity of 100% and a specificity of 93%. These data showed high agreement between conventional testing and our novel real-time PCR assay. Furthermore, this assay significantly reduced the time needed for identification. In conclusion, using pathogen-specific probes offers a faster alternative for pathogen detection and could improve the diagnosis of bloodstream infections.     

Antimicrobial activity of doripenem (S-4661): a global surveillance report (2003)

The spectrum of activity and potency of doripenem, a broad-spectrum parenteral carbapenem currently in clinical development, was evaluated using 16 008 clinical bacterial isolates collected as part of an international surveillance project during 2003. Using reference broth microdilution methods, doripenem was found to be highly active against oxacillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci (2705 and 297 isolates, respectively; MIC90s 0.06 mg/L), with a potency greater than that of other carbapenem antibiotics. Against enterococci (1474 isolates), with the exception of Enterococcus faecium, doripenem displayed modest activity (MIC50 4). Doripenem was among the most potent agents tested against Streptococcus pneumoniae, viridans group streptococci and beta-haemolytic streptococci (885, 140 and 397 isolates; MIC(90)s 0.5, 0.5 and 0.03 mg/L, respectively). For Enterobacteriaceae (> 6200 isolates), doripenem was four- to 32-fold more active than imipenem against wild-type isolates (MIC90s 0.03-0.5 mg/L). MIC90s for confirmed extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae (121 and 155 isolates; 0.06 and 0.12 mg/L, respectively) were two-fold higher than for wild-type isolates. Doripenem was also active against Citrobacter spp., Enterobacter spp. and Serratia spp. (MIC90s 0.06-0.25 mg/L), including ceftazidime-resistant isolates. Doripenem and meropenem were the most active agents among all beta-lactams against Pseudomonas aeruginosa (829 isolates; MIC50/90s 0.5/8 and 0.5/16 mg/L, respectively), whereas doripenem and imipenem were the most active agents against Acinetobacter spp. (155 isolates; MIC50/90s 0.5/4 and 相似文献   

The DUEL study: a multi-center in vitro evaluation of linezolid compared with other antibiotics in the Netherlands

Objective   To evaluate bacterial susceptibility to linezolid in the Netherlands in comparison with other antibiotics.
Methods   Bacterial strains were isolated between September 1999 and January 2000 from patients presumed to require antibiotic treatment. The in vitro activity of 1226 strains from 34 participating laboratories was tested against linezolid, vancomycin, teicoplanin, oxacillin, penicillin, erythromycin, ampicillin and other antibiotics against enterococci, coagulase-negative staphylococci, Staphylococcus aureus and Streptococcus pneumoniae . Minimal inhibitory concentrations (MIC) were obtained with the E test on Mueller-Hinton agar: every laboratory included control strains. For vancomycin and teicoplanin only, brain–heart infusion agar and an inoculum of 2.0 McFarland was used for Staphylococcus aureus , coagulase-negative staphylococci and enterococci to support a better growth and clear recognition of hetero-resistant colonies.
Results   The values of MIC₉₀ for linezolid were 1.5, 0.75, 0.75 and 1 mg/L for Staphylococcus aureus , coagulase-negative staphylococci, Streptococcus pneumoniae and enterococci, respectively. Six enterococcal strains with decreased susceptibility against vancomycin or teicoplanin were identified as Enterococcus faecium , E. gallinarum and E. casseliflavus (two strains each) and they were found to harbor vanA , vanC1 and vanC2/3 genes, respectively. Nine per cent of Streptococcus pneumoniae (an increase from 1% 4 years ago) showed decreased susceptibility to erythromycin, of both the ermB and mefE type; there was no cross-resistance with linezolid. Twelve coagulase-negative staphylococcal strains were resistant to teicoplanin.
Conclusion   Linezolid is a promising drug in the treatment of infections caused by Gram-positive cocci. Cross-resistance with other antibiotics tested was not found.     

Rapid culture and identification: a practical method for early preliminary laboratory diagnosis of sepsis.

This study describes the development of a method for rapid preliminary species identification of bacteria from positive blood culture vials. The method yielded preliminary identification results for 496 (92%) of 541 positive blood cultures within 5 h. The method was capable of identifying the most frequently isolated bacteria (i.e., Staphylococcus aureus, coagulase-negative staphylococci, Escherichia coli, Streptococcus pneumoniae and Enterococcus spp.) to the species level. The method can be established easily, with a materials cost of 2-5 Euros per sample.     

Rapid Detection of Methicillin Resistance in Staphylococcus aureus Isolates by the MRSA-Screen Latex Agglutination Test

The slide agglutination test MRSA-Screen (Denka Seiken Co., Niigata, Japan) was compared with the mecA PCR ("gold standard") for the detection of methicillin resistance in Staphylococcus aureus. The MRSA-Screen test detected the penicillin-binding protein 2a (PBP2a) antigen in 87 of 90 genetically diverse methicillin-resistant S. aureus (MRSA) stock culture strains, leading to a sensitivity of 97%. The three discrepant MRSA strains displayed positive results only after induction of the mecA gene by exposure to methicillin. Both mecA PCR and MRSA-Screen displayed negative results among the methicillin-susceptible S. aureus strains (n = 106), as well as for Micrococcus spp. (n = 10), members of the family Enterobacteriaceae (n = 10), Streptococcus pneumoniae (n = 10), and Enterococcus spp. (n = 10) (specificity = 100%). Producing the same PBP2a antigen, all 10 methicillin-resistant Staphylococcus epidermidis strains score positived in both the latex test and the mecA PCR. Consequently, the MRSA-Screen test should be applied only after identification of the MRSA strain to the species level to rule out coagulase-negative staphylococci. In conclusion, due to excellent specificity and sensitivity the MRSA-Screen latex test has the potential to be successfully used for routine applications in the microbiology laboratory.     

Further increase of vancomycin-resistant Enterococcus faecium, amikacin- and fluoroquinolone-resistant Klebsiella pneumoniae, and imipenem-resistant Acinetobacter spp. in Korea: 2003 KONSAR surveillance

Monitoring temporal trends of antimicrobial resistance can provide useful information for the empirical selection of antimicrobial agents to treat infected patients and for the control of nosocomial infections. In this study, we analyzed antimicrobial resistance of clinically relevant bacteria in 2003 at Korean hospitals and at a commercial laboratory. The following organism-antimicrobial agent resistance combinations were very prevalent: oxacillin-resistant Staphylococcus aureus (68%), expanded-spectrum cephalosporin-resistant Klebsiella pneumoniae (25%), and fluoroquinolone-resistant Escherichia coli (33%), Acinetobacter spp. (58%), and Pseudomonas aeruginosa (40%). Moreover, gradual increases in vancomycin-resistant Enterococcus faecium (20%), cefoxitin-resistant E. coli (10%) and K. pneumoniae (23%), and imipenem-resistant P. aeruginosa (20%) and Acinetobacter spp. (13%) were also observed. The resistance rates of Acinetobacter spp. to most antimicrobial agents at hospitals and at the commercial laboratory were similar. Among the Acinetobacter spp. isolated at a tertiary-care hospital, 46.2% were multidrug-resistant to 9-12 of 13 antimicrobial agents, and 18.3% were panresistant. The exclusion of duplicate isolates at a tertiary-care hospital significantly lowered the proportion of oxacillin-resistant S. aureus, vancomycin-resistant E. faecium, and fluoroquinolone-resistant E. coli.     

The changing epidemiology of severe infections in the ICU

Data on the epidemiology of severe infection in the intensive care unit (ICU) can be used to monitor the effect of preventive measures and changes in policy or procedures. The most common risk factors associated with ICU-acquired infection include length of stay, antibiotic usage, catheterization and use of other invasive devices. The most frequent infections encountered in ICU patients include lower respiratory tract infections (especially pneumonia) and bacteremia, in addition to urinary tract infections and wound infections. Streptococcus pneumoniae, Haemophilus influenzae , methicillin susceptible Staphylococcus aureus and Enterobacteriaceae are most often implicated in community-acquired and early onset ICU-acquired infections, whereas late onset infection is more likely to be caused by pathogens which are more refractory to treatment, such as Enterobacter spp., Serratia spp., Pseudomonas aeruginosa, Acinetobacter spp. and methicillin-resistant S. aureus (MRSA). The pathogen spectrum also varies according to the site of infection, with Gram-positive bacteria being most frequently isolated in bacteremia and wound infections, whereas Gram-negative bacteria are prevalent in late-onset pneumonia and urinary tract infections. The prevalence of Gram-positive pathogens in bacteremia has increased over the past 20 years, mainly because of the increased isolation of coagulase-negative staphylococci (CNS) and enterococci. This is most probably due to the selective pressure exerted by the use of broad-spectrum antibiotics, such as the third-generation cephalosporins and fluoroquinolones, which are generally more potent against Gram-negative than Gram-positive bacteria, and to the increased use of invasive devices.
The increasing isolation frequency of Gram-positive pathogens in severe ICU infections has resulted in greater usage of vancomycin, which may account for the rising incidence of vancomycin-resistant enterococci.