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Multicenter survey of the changing in vitro antimicrobial susceptibilities of clinical isolates of Bacteroides fragilis group, Prevotella, Fusobacterium, Porphyromonas, and Peptostreptococcus species.

In vitro surveys of antimicrobial resistance among clinically important anaerobes are an important source of information that can be used for clinical decisions in the choice of empiric antimicrobial therapy. This study surveyed the susceptibilities of 556 clinical anaerobic isolates from four large medical centers using a broth microdilution method. Piperacillin-tazobactam was the only antimicrobial agent to which all the isolates were susceptible. Similarly, imipenem, meropenem, and metronidazole were highly active (resistance, <0.5%), whereas the lowest susceptibility rates were noted for penicillin G, ciprofloxacin, and clindamycin. For most antibiotics, blood isolates were less susceptible than isolates from intra-abdominal, obstetric-gynecologic, and other sources. All isolates of the Bacteroides fragilis group were susceptible to piperacillin-tazobactam and metronidazole, while resistance to imipenem and meropenem was low (<2%). For these same isolates, resistance rates (intermediate and resistant MICs) to ampicillin-sulbactam, cefoxitin, trovafloxacin, and clindamycin were 11, 8, 7, and 29%, respectively. Among the individual species of the B. fragilis group, the highest resistance rates were noted among the following organism-drug combinations: for clindamycin, Bacteroides distasonis and Bacteroides ovatus; for cefoxitin, Bacteroides thetaiotaomicron, B. distasonis, and Bacteroides uniformis; for ampicillin-sulbactam, B. distasonis, B. ovatus, and B. uniformis; and for trovafloxacin, Bacteroides vulgatus. For the carbapenens, imipenem resistance was noted among B. fragilis and meropenem resistance was seen among B. fragilis, B. vulgatus, and B. uniformis. With few exceptions all antimicrobial agents were highly active against isolates of Prevotella, Fusobacterium, Porphyromonas, and Peptostreptococcus. These data further establish and confirm that clinically important anaerobes can vary widely in their antimicrobial susceptibilities. Fortunately most antimicrobial agents were active against the test isolates. However, concern is warranted for what appears to be a significant increases in resistance to ampicillin-sulbactam and clindamycin.

Bacterial Infections↗

Carbapenem resistance in a clinical isolate of Enterobacter aerogenes is associated with decreased expression of OmpF and OmpC porin analogs.

We investigated the mechanism of imipenem resistance in Enterobacter aerogenes strain 810, a clinical isolate from the United States for which the imipenem MIC was 16 micro g/ml and the meropenem MIC was 8 micro g/ml. An imipenem-susceptible revertant, strain 810-REV, was obtained after multiple passages of the strain on nonselective media. For the revertant, the imipenem MIC was </=1 micro g/ml and the meropenem MIC was </=0.25 micro g/ml. Cefepime MICs also decreased from 8 to 1 micro g/ml; however, the MICs of ceftazidime (>/=128 micro g/ml), cefoxitin (>/=32 micro g/ml), and cefotaxime (>/=64 micro g/ml) remained the same. The beta-lactamase and porin profiles of the parent, the revertant, and carbapenem-susceptible type strain E. aerogenes ATCC 13048 were determined. Strains 810 and 810-REV each produced two beta-lactamases with pIs of 8.2 and 5.4. The beta-lactamase activities of the parent and revertant were similar, even after induction with subinhibitory concentrations of imipenem. While 810-REV produced two major outer membrane proteins of 42 and 39 kDa that corresponded to Escherichia coli porins OmpC and OmpF, respectively, the parent strain appeared to produce similar quantities of the 39-kDa protein (OmpF) but decreased amounts of the 42-kDa protein (OmpC). When the parent strain was grown in the presence of imipenem, the 42-kDa protein was not detectable by gel electrophoresis. However, Western blot analysis of the outer membrane proteins of the parent and revertant with polyclonal antisera raised to the OmpC and OmpF analogs of Klebsiella pneumoniae (anti-OmpK36 and anti-OmpK35, respectively) showed that strain 810 expressed only the 42-kDa OmpC analog in the absence of imipenem (the 39-kDa protein was not recognized by the anti-OmpF antisera) and neither the OmpC nor the OmpF analog in the presence of imipenem. The OmpC analog is apparently down-regulated in the presence of imipenem; however, 810-REV expressed both OmpC and OmpF analogs. These data suggest that imipenem resistance in E. aerogenes 810 is primarily associated with the lack of expression of the analogs of the OmpC (42-kDa) and OmpF (39-kDa) outer membrane proteins, which also results in decreased susceptibility to meropenem and cefepime.

Carbapenems↗

Comparative intracellular (THP-1 macrophage) and extracellular activities of beta-lactams, azithromycin, gentamicin, and fluoroquinolones against Listeria monocytogenes at clinically relevant concentrations.

The activities of ampicillin, meropenem, azithromycin, gentamicin, ciprofloxacin, and moxifloxacin against intracellular hemolysin-positive Listeria monocytogenes were measured in human THP-1 macrophages and were compared with the extracellular activities observed in broth. All extracellular concentrations were adjusted to explore ranges that are clinically achievable in human serum upon conventional therapy. In broth, ampicillin, meropenem, and azithromycin were only bacteriostatic, whereas gentamicin, ciprofloxacin, and moxifloxacin were strongly bactericidal in a concentration-dependent manner. In cells, ampicillin, meropenem, azithromycin, and ciprofloxacin were slightly bactericidal (0.3- to 0.8-log CFU reductions), moxifloxacin was strongly bactericidal (2.1-log CFU reduction), and gentamicin was virtually inactive. The difference in the efficacies of moxifloxacin and ciprofloxacin in cells did not result from a difference in levels of accumulation in cells (6.96 +/- 1.05 versus 7.75 +/- 1.03) and was only partially explainable by the difference in the MICs (0.58 +/- 0.04 versus 1.40 +/- 0.17 mg/liter). Further analysis showed that intracellular moxifloxacin expressed only approximately 1/7 of the activity demonstrated against extracellular bacteria and ciprofloxacin expressed only 1/15 of the activity demonstrated against extracellular bacteria. Gentamicin did not increase the intracellular activities of the other antibiotics tested. The data suggest (i) that moxifloxacin could be of potential interest for eradication of the intracellular forms of L. monocytogenes, (ii) that the cellular accumulation of an antibiotic is not the only determinant of its intracellular activity (for fluoroquinolones, it is actually a self-defeating process as far as activity is concerned), and (iii) that pharmacodynamics (activity-to-concentration relationships) need to be considered for the establishment of efficacy against intracellular bacteria, just as they are for the establishment of efficacy against extracellular infections.

Anti-Bacterial Agents↗

Surveillance for antimicrobial susceptibility among clinical isolates of Pseudomonas aeruginosa and Acinetobacter baumannii from hospitalized patients in the United States, 1998 to 2001.

Pseudomonas aeruginosa and Acinetobacter baumannii are the most prevalent nonfermentative bacterial species isolated from clinical specimens of hospitalized patients. A surveillance study of 65 laboratories in the United States from 1998 to 2001 found >90% of isolates of P. aeruginosa from hospitalized patients to be susceptible to amikacin and piperacillin-tazobactam; 80 to 90% of isolates to be susceptible to cefepime, ceftazidime, imipenem, and meropenem; and 70 to 80% of isolates to be susceptible to ciprofloxacin, gentamicin, levofloxacin, and ticarcillin-clavulanate. From 1998 to 2001, decreases in antimicrobial susceptibility (percents) among non-intensive-care-unit (non-ICU) inpatients and ICU patients, respectively, were greatest for ciprofloxacin (6.1 and 6.5), levofloxacin (6.6 and 3.5), and ceftazidime (4.8 and 3.3). Combined 1998 to 2001 results for A. baumannii isolated from non-ICU inpatients and ICU patients, respectively, demonstrated that >90% of isolates tested were susceptible to imipenem (96.5 and 96.6%) and meropenem (91.6 and 91.7%); fewer isolates from both non-ICU inpatients and ICU patients were susceptible to amikacin and ticarcillin-clavulanate (70 to 80% susceptible); and <60% of isolates were susceptible to ceftazidime, ciprofloxacin, gentamicin, or levofloxacin. From 1998 to 2001, rates of multidrug resistance (resistance to at least three of the drugs ceftazidime, ciprofloxacin, gentamicin, and imipenem) showed small increases among P. aeruginosa strains isolated from non-ICU inpatients (5.5 to 7.0%) and ICU patients (7.4 to 9.1%). From 1998 to 2001, rates of multidrug resistance among A. baumannii strains isolated from non-ICU inpatients (27.6 to 32.5%) and ICU patients (11.6 to 24.2%) were higher and more variable than those observed for P. aeruginosa. Isolates concurrently susceptible, intermediate, or resistant to both imipenem and meropenem accounted for 89.8 and 91.2% of P. aeruginosa and A. baumannii isolates, respectively, studied from 1998 to 2001. In conclusion, for aminoglycosides and most beta-lactams susceptibility rates for P. aeruginosa and A. baumannii were constant or decreased only marginally (</=3%) from 1998 to 2001. Greater decreases in susceptibility rates were, however, observed for fluoroquinolones and ceftazidime among P. aeruginosa isolates.

Acinetobacter baumannii↗

Doripenem.

Doripenem is a new member of the carbapenem class of beta-lactam antibiotics with broad-spectrum coverage of Gram-positive, Gram-negative and anaerobic pathogens similar to imipenem and, especially, meropenem. This parenteral antibiotic may offer slightly more activity than meropenem against selected pathogens, including coverage of some strains of Pseudomonas aeruginosa strains not susceptible to the other antipseudomonal carbapenems. Empiric therapy with doripenem, as with other antipseudomonal carbapenems, may be useful in hospital and intensive care unit settings where multidrug resistance has emerged, especially in Gram-negative enteric pathogens. When P. aeruginosa or multidrug-resistant Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci are involved, doripenem must be used in combination. Doripenem has a broad spectrum of activity against many common hospital pathogens, including P. aeruginosa and Burkholderia cepacia, which is similar to meropenem.

Bacteria, Anaerobic↗

Antimicrobial susceptibility patterns of unusual nonfermentative gram-negative bacilli isolated from Latin America: report from the SENTRY Antimicrobial Surveillance Program (1997-2002).

The antimicrobial susceptibility of 176 unusual non-fermentative gram-negative bacilli (NF-GNB) collected from Latin America region through the SENTRY Program between 1997 and 2002 was evaluated by broth microdilution according to the National Committee for Clinical Laboratory Standards (NCCLS) recommendations. Nearly 74% of the NF-BGN belonged to the following genera/species: Burkholderia spp. (83), Achromobacter spp. (25), Ralstonia pickettii (16), Alcaligenes spp. (12), and Cryseobacterium spp. (12). Generally, trimethoprim/sulfamethoxazole (MIC50, < 0.5 microg/ml) was the most potent drug followed by levofloxacin (MIC50, 0.5 microg/ml), and gatifloxacin (MIC50, 1 microg/ml). The highest susceptibility rates were observed for levofloxacin (78.3%), gatifloxacin (75.6%), and meropenem (72.6%). Ceftazidime (MIC50, 4 microg/ml; 83.1% susceptible) was the most active beta-lactam against B. cepacia. Against Achromobacter spp. isolates, meropenem (MIC50, 0.25 microg/ml; 88% susceptible) was more active than imipenem (MIC50, 2 microg/ml). Cefepime (MIC50, 2 microg/ml; 81.3% susceptible), and imipenem (MIC50, 2 microg/ml; 81.3% susceptible) were more active than ceftazidime (MIC50, >16 microg/ml; 18.8% susceptible) and meropenem (MIC50, 8 microg/ml; 50% susceptible) against Ralstonia pickettii. Since selection of the most appropriate antimicrobial agents for testing and reporting has not been established by the NCCLS for many of NF-GNB species, results from large multicenter studies may help to guide the best empiric therapy.

Anti-Bacterial Agents↗

[Evaluation of in vitro activity of new fluoroquinolones, cephalosporins and carbapenems against 569 gram-negative bacteria].

OBJECTIVE: Evaluation of the in vitro activity of new fluoroquinolones, cephalosporins and carbapenems against gram-negative bacteria. MATERIAL AND METHOD: A total of 569 clinical isolates were obtained from inpatients at São Paulo Hospital--UNIFESP/EPM in June and July of 1992. The species distribution was as follows: Enterobacter sp. (62), Escherichia coli (308), Klebsiella pneumoniae (27), Klebsiella sp. (9), Proteus mirabilis (23), Pseudomonas aeruginosa (88), Pseudomonas sp. (4), Serratia sp. (30) and other gram-negatives (7). Susceptibility tests were performed by broth microdilution. The antimicrobials agents tested were: ciprofloxacin, ofloxacin, levofloxacin, grepafloxacin, DU 6859-alpha, ceftazidime, cefepime, FK 037, imipenem, meropenem and biapenem. RESULTS: DU 6859-alpha showed the highest anti-microbial activity among the fluoroquinolones. It was two- to four-fold more active than ciprofloxacin against some species. The potency and antimicrobial spectrum were similar between the fourth-generation cephalosporins against Enterobacteriaceae, except for Enterobacter sp. strains which were more susceptible to cefepime than they were to cefetazidime or FK 037. When testing Pseudomonas aeruginosa, ceftazidime was slightly more active than the other cephalosporins. Against Enterobacteriaceae and Pseudomonas aeruginosa strains, meropenem was more active than imipenem or biapenem. In addition, the percentage of strains, susceptible to meropenem was higher than the percentage susceptible to the other cerbapenems against these species. CONCLUSION: The new antimicrobial agents demonstrated in vitro activity higher than that of agents commercially available. However, more studies are necessary to further evaluate the in vivo activity and the clinical benefit of these compounds.

Anti-Infective Agents↗

Antimicrobial susceptibility in intensive care units: MYSTIC Program Brazil 2002.

OBJECTIVE: Establish the susceptibility pattern of Gram-negative bacteria causing infections in ICU patients, MYSTIC Program Brazil 2002. MATERIAL AND METHODS: Gram-negative bacteria (n = 503) causing nosocomial infections were collected at seven Brazilian centers. The central laboratory confirmed the identification and performed the susceptibility tests by E-test methodology (AB Biodisk, Solna, Sweden) for meropenem, imipenem, ciprofloxacin, ceftazidime, cefepime, cefotaxime, piperacillin/tazobactam, gentamicin, and tobramycin. Interpretation criteria used were according to National Committee for Clinical Laboratory Standards (NCCLS). RESULTS: Pseudomonas aeruginosa (33%) was the most frequently isolated, followed by A. baumannii (17.1%), K. pneumoniae (12.1%), E. coli (10.5%), and E. cloacae (7.9%). Pseudomonas aeruginosa isolates had susceptibility rates of 67.5% to piperacillin/tazobactam, 59.8% to meropenem, 57.3% to imipenem. A. baumannii presented susceptibility rates to meropenem of 89.5%, 88.4% to imipenem, and 74.4% to tobramycin. E. coli and K. pneumoniae were fully susceptible to both carbapenems. CONCLUSIONS: Carbapenem resistance among Enterobacteriaceae is still rare in this region. A. baumannii and P. aeruginosa presented elevated resistance rates to all antimicrobials. Since these two bacterial species play an important role in nosocomial infections, the use of empirical combination therapy to treat these pathogens may be justified.

Anti-Bacterial Agents↗

Antimicrobial susceptibility of Gram-negative bacteria in Brazilian hospitals: the MYSTIC Program Brazil 2003.

Establish the susceptibility pattern of Gram-negative bacteria causing infections in ICU patients, MYSTIC Program Brazil 2003. Gram-negative bacteria (n = 1,550) causing nosocomial infections were collected at 20 Brazilian centers. The central laboratory confirmed the identification and performed the susceptibility tests by Etest methodology (AB Biodisk, Solna, Sweden) for meropenem, imipenem, ciprofloxacin, ceftazidime, cefepime, cefotaxime, piperacillin/tazobactam, gentamicin, and tobramycin. Interpretation criteria used were according to National Committee for Clinical Laboratory Standards (NCCLS). Pseudomonas aeruginosa (30.3%) was the most frequent isolate, followed by E. coli (18.6%), Klebsiella pneumoniae (16.9%), Acitenobacter baumannii (8.8%), and Enterobacter cloacae (7.1%). Pseudomonas aeruginosa (n=470) isolates presented susceptibility rates of 64% to meropenem, 63.8% to piperacillin/tazobactam, 63.4% to amikacin, 58.7% to imipenem. Acitenobacter baumannii presented susceptibility rates to meropenem of 97.1%, and 73% to tobramycin. E. coli and K. pneumoniae were highly susceptible to both carbapenems. Carbapenem resistance among the Enterobacteriaceae is still rare in the region. Acitenobacter baumannii and P. aeruginosa presented elevated resistance rates to all antimicrobials. Since they play an important role in nosocomial infections in this environment, the use of empirical combination therapy to treat these pathogens may be justified.

Anti-Bacterial Agents↗

Antimicrobial susceptibility of Campylobacter fetus subsp. fetus isolated from blood and synovial fluid.

Campylobacter fetus subsp. fetus is a rare human pathogen, but can cause serious extraintestinal infections. Effective antimicrobial agent is required for the therapy, but we have very limited knowledge on the susceptibility of the organism. In this study, the susceptibility of 25 isolates of the organism to 14 antimicrobial agents was tested by an agar dilution method. Antimicrobial agents with low MIC ranges, in micrograms/ml, were: meropenem < or = 0.25, dirithromycin < or = 0.5, gentamicin < or = 1, amikacin, ofloxacin, tetracycline and erythromycin < or = 2. The MIC range of cefepime was 0.5-8 micrograms/ml, but those of other beta-lactams were relatively high. All of the isolates were interpreted to be susceptible to cefepime, meropenem, amikacin, gentamicin, ofloxacin, tetracycline and dirithromycin. A significant proportion of the isolates were either intermediate or resistant to ampicillin, cephalothin, cefotaxime, aztreonam, loracarbef and erythromycin. In conclusion, the organism remains susceptible to aminoglycosides and tetracycline. Greater in vitro activity of meropenem, ofloxacin and dirithromycin require clinical evaluation.

Anti-Bacterial Agents↗

Prevalence and antimicrobial susceptibility of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in a general hospital.

BACKGROUND: The prevalence of extended-spectrum beta-lactamases (ESBLs) varies between countries and institutions. We studied the prevalence of ESBL among clinical isolates of Escherichia coli and Klebsiella pneumoniae and analyzed patterns of susceptibilities to different antimicrobial agents in a general hospital in Saudi Arabia over a 15-month period. METHODS: A total of 2455 clinical isolates of E. coli and K. pneumoniae were tested for ESBL production by double-disk diffusion. The minimum inhibitory concentration to imipenem, meropenem, piperacillin-tazobactam, cefepime, ciprofloxacin, gentamicin and amikacin were determined by the agar dilution method. RESULTS: Of the 2455 isolates of E. coli and K. pneumoniae tested, 268 (11%) produced ESBL. The ESBL phenotype was detected in 10.3% of 1674 E. coli isolates and 12.2% of 781 K. pneumoniae isolates. The majority of these isolates were from urine (57.5%) and wounds (17%). Only 7% of the blood culture isolates were ESBL-producing. Overall, carbapenems (imipenem and meropenem) had good activity against the ESBL-producing isolates tested (over 92% of isolates were susceptible). There was no difference in the activity of imipenem and meropenem against the ESBL-producing E. coli or K. pneumoniae. Over 66% of the isolates were susceptible to piperacillin-tazobactam. Susceptibilities of the isolates to amikacin varied, ranging from 72.8% for E. coli to 62% for K. pneumoniae. Gentamicin, ciprofloxacin and cefepime were active against 58.6%, 55% and 22.8% of the isolates, respectively. CONCLUSION: Our findings demonstrate the increasing incidence of infection with ESBL-producing bacteria, and the high rates of antimicrobial resistance encountered among them. Clinicians should be familiar with the clinical importance of these enzymes and potential strategies for dealing with them.

Anti-Bacterial Agents↗

Structure-activity relationships of carbapenems to the antagonism of the antipseudomonal activity of other beta-lactam agents and to the beta-lactamase inducibility in Pseudomonas aeruginosa: effects of 1beta-methyl group and C-2 side chain.

The antagonism of the antipseudomonal activity of ceftazidime by meropenem (1a) was much less than those by imipenem (2a) and panipenem (2b). To reveal the major structural features of carbapenem compounds responsible for the antagonism, we investigated the structure-activity relationships of carbapenems to their antagonism of the antipseudomonal activity of ceftazidime and to their beta-lactamase-inducibility in P. aeruginosa. The antagonistic effect of 1a was less than that of desmethyl-meropenem (1b). Two other meropenem-analogues (3, 4), with the highly basic C-2 side chain, showed greater antagonistic effects than that of 1a, which has a weakly basic C-2 side chain. The beta-lactamase-inducibility of 1a in P. aeruginosa was lower than those of 2a, 1b and 4. These results indicated that the antagonism of the antipseudomonal activity of ceftazidime by carbapenems was due to the induction of beta-lactamase in P. aeruginosa. As a result of the study on the structure-activity relationships, we clarified that the introduction of a 1beta-methyl group and/or the reduction of the basicity (cationic character) of the C-2 side chain in carbapenem skeleton decreased the antagonistic effect of carbapenems on the antipseudomonal activity of ceftazidime resulted mainly from the decreasing the beta-lactamase inducibility.

Carbapenems↗

[In vitro activity of piperacillin-tazobactam against Klebsiella pneumoniae clinical isolates, producers or not of extended spectrum beta-lactamases].

The aim of this study was to determine the in vitro activity of piperacillin-tazobactam against 81 clinical isolates of Klebsiella pneumoniae. The clinical specimens were processed according to standard microbiological procedures and 81 K. pneumoniae isolates were identified using MicroScan Panels following the manufacturer's recommendations. A double disk diffusion method was applied to detect extended spectrum betalactamases (ESBL) (43 isolates were positive and 38 were negative). Minimum inhibitory concentrations (MIC) were determined by an agar dilution technique using Mueller-Hinton. The following antibiotics were studied: piperacillin with 4 mg/l of tazobactam, amoxicillin-clavulanic acid in a 2:1 proportion, cefotaxime, ceftriaxone, cefepime, imipenem and meropenem. The MIC(90) were 16/4 mg/l for piperacillin-tazobactam, 16/8 for amoxicillin-clavulanic acid, 16 for ceftriaxone, 16 for cefotaxime, 4 for cefepime, 0.25 for imipenem and 0.032 for meropenem in ESBL-positive strains. In ESBL-negative strains the MIC90 were as follows: 4/4 mg/l for piperacillin-tazobactam, 8/4 for amoxicillin-clavulanic acid, 0.064 for ceftriaxone, 0.125 for cefotaxime, 0.125 for cefepime, 0.125 for imipenem and 0.016 for meropenem. All betalactams showed excellent in vitro activity against ESBL non-producer K. pneumoniae. Moreover, piperacillin-tazobactam and both carbapenems showed good in vitro activity against EBSL-producer K. pneumoniae.

Drug Therapy, Combination↗

Preface.

Efficient monitoring for the emergence of resistance to various antimicrobial agents has, in the face of global trends in resistance, recently assumed great importance. Many programmes have been developed to survey resistance, each varying in scope or emphasis as well as commitment to long-term monitoring. A programme that specifically addresses pathogens from populations of the most severely ill patients is the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC). This programme was started in 1997 to monitor carbapenem activity in vitro in centres using carbapenems because their prevalent strains were resistant to other beta-lactams and drug classes. Meropenem is a broad-spectrum carbapenem and differs microbiologically from imipenem by having a greater potency in vitro against many Gram-negative pathogens and a slightly lower potency against some Gram-positive pathogens. Meropenem has improved stability to renal-based enzymatic metabolism, and does not require the addition of an enzyme inhibitor such as cilastatin. Material in this publication is based on the many abstracts and oral presentations delivered at recent national and international meetings including: the International Congress of Infectious Disease in Buenos Aires, Argentina (April, 2000); the European Congress of Chemotherapy in Madrid, Spain (May, 2000); and the European Congress of Clinical Microbiology and Infectious Disease in Stockholm, Sweden (May, 2000). All of the authors are active participants in the MYSTIC programme and bring to it experience in the design of surveillance studies and the detection of resistance mechanisms. Professor Jones discusses the most useful ways of storing and presenting susceptibility data to preserve the long-term value of all results. He argues for the publication of expanded study details and the limited use of MIC(90) values or susceptibility rates. Dr Turner has coordinated the MYSTIC programme, and he summarizes here the similarities and differences in the results seen to date between the Americas, Europe and centres in Asia and the Middle East. The Americas have been one of the most recently monitored regions. Professors Pfaller and Jones give baseline data for the USA (10 sites), Mexico and Brazil. Professor Goossen's article focuses on the results of MYSTIC in the European centres. Doctor Masterton presents a comprehensive overview of various surveillance studies and assesses their value and characteristics for the continued optimal management of infected patients.

Journal Article↗

Evaluation of the in vitro activity of 9 antimicrobials against bacterial strains isolated from patients in intensive care units in brazil: MYSTIC Antimicrobial Surveillance Program.

Multi-resistant bacterial strains are increasingly prevalent in hospital environments. Bacterial resistance is an important problem, especially for practitioners in intensive care units (ICUs) because of the selective pressure on the prevalent bacteria in these environments. The MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) study has been monitoring the performance of carbapenems and other antibiotics in different hospitals for at least 3 years. The in vitro activities of meropenem, imipenem, ceftazidime, cefepime, cefotaxime, ciprofloxacin, piperacilin/tazobactam, gentamicin, and tobramycin were compared against 452 recent clinical aerobic isolates. The isolates consisted of 19 species of Gram-negative bacteria (n=290) including K. pneumoniae (n=49), E. coli (n=48), A. baumannii (n=47), Enterobacter spp. (n=41), and P. aeruginosa (n=33) and 9 species of Gram-positive bacteria (n=162) including Staphylococcus aureus (n=63), Enterococcus faecalis (n=22), Streptococcus pneumoniae (n=22) and coagulase negative Staphylococci (n=21). All isolates were collected from ICU patients. Minimal inhibitory concentrations (MICs) were determined by Etest methodology, using standardized and controlled procedures. Meropenem and imipenem showed the lowest MIC(90) for all species tested. Gram-negative isolates showed the following overall resistance percentages to the other 7 drugs: tobramycin (43.1%), cefotaxime (38.6%), gentamicin (34.1%), ceftazidime (31.7%), ciprofloxacin (25.5%), piperacillin/tazobactam (26.9%), and cefepime (18.6%). Carbapenems were the most active drugs overall and only P. aeruginosa presented some degree of resistance (18.2%). We also evaluated the production of extended spectrum beta-lactamase (ESBL) among all Enterobacteriaceae members (n=176) by Etest/ESBL strip. ESBL production was detected in 51 strains (29.0%). Among them, Klebsiella pneumoniae was the most prevalent at 59.2%, followed by Enterobacter spp. (19.5%) and E. coli (14.6%). The high level of resistance against several antimicrobials and the alarming rate of ESBL production may restrict therapeutic choice to the carbapenems in this selected group of patients.

Anti-Bacterial Agents↗

[Antimicrobial susceptibilities of organisms isolated from patients with urinary tract infections in 2002].

Using the agar dilution method, the antibacterial activity of 18 antibiotics inclusive of 4 carbapenems were investigated against 101 strains of urinary pathogens isolated from patients with urinary tract infections who visited the Department of Urology at Kagoshima University Hospital, between January and December 2002. 4 strains of Staphylococcus aureus, 3 strains of Staphylococcus spp. (exclusive of S. aureus), 14 strains of Enterococcus faecalis, 3 strains of Enterococcus spp. (exclusive of E. faecalis), 41 strains of Escherichia coli, 21 strains of Enterobacteriaceae (exclusive of E. coli), 12 strains of Pseudomonas aeruginosa and 3 strains of glucose-nonfermentative Gram-negative rods (exclusive of P. aeruginosa) were examined. 1. Against clinical isolates of Gram-positive bacteria, vancomycin and teicoplanin were active. Additionally, arbekacin was active against S. aureus clinical isolates and ampicillin was active against E. faecalis clinical isolates. Carbapenems were active against clinical isolates of Gram-positive bacteria, except for multi-drug resistant strains of Gram-positive bacteria, such as methicillin-resistant S. aureus. 2. As for clinical isolates of Gram-negative bacteria, meropenem was most active against Enterobacteriaceae among 13 antibiotics tested. Against P. aeruginosa clinical isolates, MIC90 of meropenem was the lowest among 13 antibiotics tested. In addition, resistant rate of meropenem and biapenem against P. aeruginosa clinical isolates was lower than those of the other carbapenems tested. 3. As main urinary pathogens showed no remarkable increase in resistance to carbapenems, it can be stated that carbapenems retain their position as the drug of first choice for severe infection.

Anti-Bacterial Agents↗

[E-test to study small inhibitor concentrations, bacterial diversity and to identify presumptively beta-lactamases in strains of Pseudomonas aeruginosa and Acinetobacter baumannii associated with +nosocomial infections].

BACKGROUND: Pseudomonas aeruginosa and Acinetobacter baumanii are two important nosocomial agents that require permanent testing of their antimicrobial susceptibility. AIM: To use E-test to determine minimal inhibitory concentrations, estimate bacterial diversity and presumably identify B-lactamases of strains of Pseudomonas aeruginosa and Acinetobacter baumanii isolated from nosocomial infections. MATERIALS AND METHODS: Sixty eight strains of Pseudomonas aeruginosa and Acinetobacter baumanii isolated in a teaching hospital were analyzed with E-test strips to determine their minimal inhibitory concentrations for different antimicrobials. RESULTS: More than 75% of Acinetobacter baumanii were resistant to Piperacillin, Cefpirome, Cefepime, Gentamicin or Amikacin, 40% of strains were resistant to Ceftazidime, 27 and 53% of isolates had a decreased susceptibility to Meropenem and Piperacillin-tazobactam respectively. Twenty eight to 54% of Pseudomonas aeruginosa strains were resistant to Cefepime, Cefpirome, Ciprofloxacin and Gentamicin. Eighteen and 10% of strains were resistant to Meropenem and Imipenem respectively. Less than 10% of strains were resistant to Amikacin, Azireonam, Piperacillin-tazobactam or Ceftazidime. Most of beta-lactam resistance of Pseudomonas aeruginosa was associated to decreased susceptibility or resistance to Cefpirome, Cefepime or to Meropenem-Imipenem and did not match clearly with known beta-lactamase profiles. CONCLUSIONS: The knowledge of susceptibility of these bacteria responsible for nosocomial infections, will help to plan the appropriate use of antimicrobials.

Acinetobacter↗

[Susceptibility of clinical strains of gram-negative rods to selected beta-lactam antibiotics].

The aim of the study was to determine the activity of four beta-lactam antibiotics against nosocomial strains of gram-negative bacilli. Two antibiotics combined with beta-lactamase inhibitors: timentin (TIC/CLAV) and tazocin (PIP/TZB) and two carbapenems: imipenem and meropenem were applied. The clinical strains were isolated from patients hospitalized in the following wards: surgery and intensive care unit of State Clinical Hospital No 1 in Warsaw. The strains were identified in the automatic ATB system using ID 32 E and ID 32 GN strips. The susceptibility of isolates to antibacterial agents was determined in the automatic ATB system using ATB G- and ATB PSE strips. The susceptibility of the strains to imipenem, meropenem, timentin and tazocin was tested by disc-diffusion method. 157 strains of gram-negative bacilli were cultured. 100 strains were isolated from patients hospitalized in surgical ward and 57 strains from patients hospitalized in ICU. Nonfermenting rods dominated among isolated strains-91. The results obtained indicate that multiresistant gram-negative rods causing serious therapeutic problems are often isolated from clinical specimens. The contribution of nonfermenting rods, especially Pseudomonas spp. and Acinetobacter spp. to the etiology of infections in hospitalized patients has increased. Infections caused by these strains are difficult to cure. Tazocin and carbapenems (imipenem and meropenem) are highly active in vitro against the examined strains of gram-negative bacilli.

Anti-Bacterial Agents↗