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PubMed2003

Antimicrobial activity against strains of Escherichia coli and Klebsiella spp. with resistance phenotypes consistent with an extended-spectrum beta-lactamase in Europe.

Extended-spectrum beta-lactamases (ESBLs) have continued to evolve after their initial detection in Europe nearly two decades ago. The summary results from the MYSTIC Program (31 medical centers) were utilized to assess the extent of ESBL occurrence in Europe from 1997 to 2000. ESBL phenotype rates in Klebsiella spp. (32.8%) and Escherichia coli (14.4%) were generally stable, but extensive hospital-to-hospital and unit-to-unit variations were noted. The highest ESBL rates were found in eastern Europe (including Turkey) and in intensive care unit patient populations. Carbapenems remained active against the ESBL-producing strains (meropenem MIC90, 0.25-1 mg/L), while some other agents, such as aminoglycosides, fluoroquinolones, and piperacillin-tazobactam, were significantly less effective. International surveillance initiatives should be maintained to monitor future progression of this important resistance.

Anti-Bacterial Agents↗

PubMed2003

Evaluation of the WIDER I system for antimicrobial susceptibility testing of clinical isolates of Haemophilus influenzae and Streptococcus pneumoniae.

The aim of this study was to evaluate the WIDER I system for susceptibility testing of Haemophilus influenzae and Streptococcus pneumoniae. MICs of 12 antimicrobials against 42 H. influenzae and 58 S. pneumoniae strains were determined using 1W MIC panels and compared with those obtained by microdilution. Overall essential agreements were >99%. Very major errors were not detected. Major errors occurred with ampicillin (1.7% H. influenzae). Minor errors were 2.3% (amoxicillin-clavulanate, cefuroxime, chloramphenicol), 7.1% (ampicillin) and 16.7% (clarithromycin) for H. influenzae, and 1.7% (chloramphenicol, erythromycin, meropenem), 3.4% (amoxicillin-clavulanate, cefuroxime, tetracycline) and 8.6% (levofloxacin) for S. pneumoniae. The WIDER I system is a reliable method for susceptibility testing of H. influenzae and S. pneumoniae.

Anti-Bacterial Agents↗

PubMed2003

Infrequent detection of acquired metallo-beta-lactamases among carbapenem-resistant Pseudomonas isolates in a Greek hospital.

OBJECTIVE: To study the possible distribution of metallo-beta-lactamases among nosocomial Pseudomonas isolates in a Greek hospital with a recent high prevalence of carbapenem-resistant Pseudomonas isolates. METHODS: All carbapenem-resistant (imipenem- and/or meropenem-resistant) (MICs > 8 mg/L) Pseudomonas non-replicate isolates recovered from clinical infections in the Microbiology Laboratory of Saint Demetrios Hospital, Thessaloniki, Greece, from April 1998 to November 2000 were studied for the presence of metallo-beta-lactamases. They were tested by a disk diffusion test, PCR analysis, and nucleotide sequencing. DNA fingerprints were obtained by pulsed-field gel electrophoresis (PFGE) of XbaI-digested chromosomal DNA. RESULTS: In total, 24 carbapenem-resistant isolates (23 P. aeruginosa and one P. putida) were recovered. The serotypes observed among the P. aeruginosa isolates were, in order of decreasing frequency, O:11 (52%), O:3 and O:12 (17% each), and O:6 (13%). PFGE grouped 17 of the P. aeruginosa isolates into four clusters, each containing from two to seven isolates, while the remaining isolates exhibited unique genotypes. blaVIM-2 was detected in the P. putida isolate and a P. aeruginosa serotype O:3 isolate. The latter strain was genotypically distinct from other contemporaneous or older carbapenem-resistant P. aeruginosa Greek isolates. CONCLUSION: These findings suggest that, although the prevalence of metallo-beta-lactamases is low, the integron-associated blaVIM genes can spread to P. aeruginosa serotypes that have not been previously associated with carbapenem resistance in our region, as well as to other pseudomonal species.

Carbapenems↗

PubMed2002

Clinical relevance of penicillin-resistant Streptococcus pneumoniae.

Streptococcus pneumoniae is the most important respiratory tract pathogen in otitis, sinusitis, bronchitis, and community-acquired pneumonia. Over the past decades, there has been an increase in minimum inhibitory concentrations (MICs) to penicillin. Decreased susceptibility to penicillin is not the same as penicillin resistance. Decreased susceptibility to penicillin has occurred worldwide from dissemination of several resistant pneumococcal clones, and, to a lesser extent, from excessive use of ciprofloxacin, macrolides, and trimethoprim-sulfamethoxazole (TMP-SMX). Currently, penicillin resistance is defined by using a breakpoint of 2 microg/mL or more. Intermediately resistant strains (MIC 1-2 microg/mL) are also relatively sensitive depending on antibiotic concentration. Intermediate antibiotic susceptibility is concentration dependent. Antibiotic concentration at various body sites is determined by pharmacokinetic considerations. Except for very highly resistant strains, the treatment of penicillin-resistant S. pneumoniae causing bacteremia, sinusitis, otitis, bronchitis, or community-acquired pneumonia remains penicillin or any beta-lactam. Only in pneumococcal meningitis caused by penicillin-resistant pneumococci does the clinician have to use care in selecting an antipneumococcal antibiotic with adequate cerebrospinal fluid penetration and favorable kill ratios. Clinicians should be selective in antibiotic selection to minimize further decreases in penicillin susceptibility to S. pneumoniae. This is best achieved by using low-resistance potential antibiotics oral/intravenous mono-therapy at the full recommended dose. Therapeutic failure may occur in using lower doses at certain body sites. Macro-lides as monotherapy or as part of combination therapy should be minimized. Optimal therapy for non-central nervous system pneumococcal infection is with a respiratory quinolone (eg, levofloxacin, gatifloxacin, moxifloxacin), clindamycin, doxycycline, third-generation cephalosporins. For highly resistant pneumococci, levofloxacin, gatifloxacin, moxifloxacin, cefepime, meropenem, vancomycin, or linezolid may be used.

Anti-Bacterial Agents↗

PubMed2002

Pseudomonas aeruginosa: resistance and therapy.

Pseudomonas aeruginosa resistance to antimicrobials is an important therapeutic consideration. Antibiotic resistance to P. aeruginosa may be chromosomally or plasmid mediated. Resistance to P. aeruginosa may also be affected by changes in the cellular membrane or intracellular environment. P. aeruginosa is primarily a nosocomial organism that most commonly colonizes respiratory secretions and urine. The selection of an antipseudomonal antibiotic depends on its inherent in vitro activity and its resistance potential. Anti-P. aeruginosa antibiotics with a high-resistance potential include gentamicin, tobramycin, ciprofloxacin, ceftazidime, and imipenem. Anti-P. aeruginosa antibiotics with a low-resistance potential include amikacin, piperacillin, cefoperazone, cefepime, meropenem, and polymyxin B.

Anti-Bacterial Agents↗

PubMed2002

Strategies to control antibiotic resistance.

Antibiotic resistance is becoming a worldwide concern. Antibiotic resistance may be caused by sporadic mutations, which are not important unless spread clonally. Clonal resistance may disseminate a highly resistant clone to widespread geographic areas. The most effective interventions to limit the clonal spread of resistant organisms are effective infection control measures. Hospital antibiotic formulary restriction is the only control measure with proven effectiveness to control resistance related to antibiotic use. Hospital formularies should eliminate or restrict antibiotics with a high-resistance potential (eg, ceftazidime, ciprofloxacin, and imipenem), and should be replaced with equivalent antibiotics with a low-resistance potential (eg, cefe-pime, levofloxacin, and meropenem). Such low-resistance-potential antibiotics can either prevent or eliminate resistance problems associated with Klebsiella pneumoniae, Enterobacter species, or Pseudomonas aeruginosa. High-resistance-potential antibiotics, particularly ciprofloxacin and ceftazidime, also may indirectly increase the prevalence of highly resistant organisms (eg, methicillin-resistant Staphylococcus aureus [MRSA], vancomycin-resistant enterococci [VRE]). Vancomycin use should be restricted, not because it increases enterococcal resistance per se, but because it selects out naturally resistant enterococcal strains (eg, Enterococcus faecium that are vancomycin resistant). Linezolid does not increase the prevalence of VRE. Clinicians in the outpatient setting should also preferentially use oral antibiotics with a low-resistance potential (eg, clindamycin, metronidazole, doxycycline, minocycline, fluoroquinolones except ciprofloxacin, linezolid, and oral cephalosporins) in preference to their high-resistance-potential counterparts. For antibiotic resistance control interventions to be effective, they must be applied simultaneously to all antibiotics with activity against the specific resistance pathogen at the hospital formulary level. Multiple antibiotic substitutions are usually necessary to eradicate resistance problems caused by a particular pathogen. Multiple drugs of the same spectrum and low-resistance potential are necessary to eliminate resistance problems; single antibiotic substitutions are not effective.

Drug Resistance, Bacterial↗

PubMed2002

Serious infections caused by enteric gram-negative bacilli--mechanisms of antibiotic resistance and implications for therapy of gram-negative sepsis in the transplanted patient.

The Enterobacteriaceae (eg, Escherichia coli, Klebsiella spp., Enterobacter spp.) are common causes of intraabdominal, respiratory tract, and bloodstream infections in transplant recipients. Antibiotic resistance in these organisms is increasing. The major mechanism of resistance to cephalosporins is beta-lactamase production. The most important beta-lactamases are the inducible group 1 cephalosporinases, which are resistant to beta-lactamase inhibitors, and the plasmid-mediated extended-spectrum beta-lactamases (ESBLs). Organisms producing these beta-lactamases also may be resistant to quinolones and aminoglycosides by different mechanisms. A worrying recent development has been the detection of plasmid-mediated carbapenemases, which can inactivate antibiotics such as imipenem and meropenem. In general, third-generation cephalosporins should be avoided in the therapy of serious infections in transplant recipients because of the common occurrence of cephalospo-rinases in the Enterobacteriaceae. Antibiotic options are becoming more limited as the prevalence of resistance mechanisms in gram-negative bacilli increases.

Bacillus↗

PubMed2000

Therapeutic considerations in the treatment of respiratory infections caused by ceftazidime-resistant Klebsiella pneumoniae.

Klebsiella pneumoniae are important human pathogens, particularly as causes of nosocomial respiratory tract infections. Intrinsically resistant to ampicillin, in recent years K. pneumoniae strains have acquired resistance to a broad variety of extended-spectrum cephalosporins. This resistance is most commonly mediated by the extended-spectrum beta-lactamases (ESBLs), plasmid-mediated enzymes that have evolved through point mutations in the genes encoding the more susceptible penicillinases TEM-1 and SHV-1. In a small minority of cases, K. pneumoniae have also been found to express extended-spectrum cephalosporin resistance by the elaboration of plasmid-mediated AmpC-type enzymes. These mutant enzymes confer resistance to extended-spectrum cephalosporins, penicillins, and in some cases cefamycins or beta-lactam-beta-lactamase inhibitor combinations. The most reliable and effective antimicrobial treatment of infections caused by these strains are the carbapenems imipenem and meropenem.

Journal Article↗

PubMed2000

Increasing prevalence of multidrug-resistant Streptococcus pneumoniae in the United States.

BACKGROUND: The emergence of drug-resistant strains of bacteria has complicated treatment decisions and may lead to treatment failures. METHODS: We examined data on invasive pneumococcal disease in patients identified from 1995 to 1998 in the Active Bacterial Core Surveillance program of the Centers for Disease Control and Prevention. Pneumococci that had a high level of resistance or had intermediate resistance according to the definitions of the National Committee for Clinical Laboratory Standards were defined as "resistant" for this analysis. RESULTS: During 1998, 4013 cases of invasive Streptococcus pneumoniae disease were reported (23 cases per 100,000 population); isolates were available for 3475 (87 percent). Overall, 24 percent of isolates from 1998 were resistant to penicillin. The proportion of isolates that were resistant to penicillin was highest in Georgia (33 percent) and Tennessee (35 percent), in children under five years of age (32 percent, vs. 21 percent for persons five or more years of age), and in whites (26 percent, vs. 22 percent for blacks). Penicillin-resistant isolates were more likely than susceptible isolates to have a high level of resistance to other antimicrobial agents. Serotypes included in the 7-valent conjugate and 23-valent pneumococcal polysaccharide vaccines accounted for 78 percent and 88 percent of penicillin-resistant strains, respectively. Between 1995 and 1998 (during which period 12,045 isolates were collected), the proportion of isolates that were resistant to three or more classes of drugs increased from 9 percent to 14 percent; there also were increases in the proportions of isolates that were resistant to penicillin (from 21 percent to 25 percent), cefotaxime (from 10 percent to 15 percent), meropenem (from 10 percent to 16 percent), erythromycin (from 11 percent to 16 percent), and trimethoprim-sulfamethoxazole (from 25 percent to 29 percent). The increases in the frequency of resistance to other antimicrobial agents occurred exclusively among penicillin-resistant isolates. CONCLUSIONS: Multidrug-resistant pneumococci are common and are increasing. Because a limited number of serotypes account for most infections with drug-resistant strains, the new conjugate vaccines offer protection against most drug-resistant strains of S. pneumoniae.

Adolescent↗

PubMed2001

Prospective study of antibacterial susceptibility, risk factors and outcome of 157 episodes of Acinetobacter baumannii bacteremia in 1999 in Slovakia.

This study prospectively investigated all 157 cases of Acinetobacter baumannii bacteremia occurring in major university hospitals or tertiary care institutions in Slovakia during 1999 in order to determine the antimicrobial susceptibility, risk factors and outcome. Resistance to meropenem was 7.4, gentamicin 35.6, amikacin 26.5, cefepime 20.4 and ciprofloxacin 32.7%, but was only 17.3% to cefoperazone/sulbactam or ampicillin/sulbactam. Antimicrobial susceptibility of A. baumanii was lowest among isolates from cancer patients (ceftazidime 58%, piperacillin/tazobactam 52% and azthreonam 48%; p < or = 0.01-0.001). In univariate analysis, several risk factors, such as wound infection (p < or = 0.01) and ventilatory support (p < or = 0.0001), were significantly related to A. baumannii bacteremia in surgical patients. Neutropenia (p < or = 0.0001), antineoplastic chemotherapy (p < or = 0.0001) and prior antibiotic therapy (p < or = 0.0006) were significant risk factors for A. baumannii bacteremia in cancer patients. In addition, ventilatory support and surgery (p < or = 0.0001) and prior antibiotic therapy (p < or = 0.01) were significantly related to A. baumannii bacteremia in children. Colonization at other body sites (p < or = 0.05), diabetes mellitus (p < or = 0.04) and decubital ulcers/burns (p < or = 0.002) as underlying disease were significantly related to death due to A. baumannii bacteremia. In a multiple logistic regression model, decubital ulcers/burns as underlying disease (p < or = 0.0006; relative risk 5.08) and nosocomial pneumonia (p < or = 0.045; relative risk 5.08) were independent predictors of mortality. Mortality was similar between cancer and surgical patients but significantly lower in children vs. adults (p < or = 0.009).

Acinetobacter↗

PubMed2005

A multi-centre prospective study of febrile neutropenia in Norway: microbiological findings and antimicrobial susceptibility.

The urgent need to treat presumptive bacterial or fungal infections in neutropenic patients has meant that initial therapy is empiric and based on the pathogens most likely to be responsible, and drug resistance. The traditional empirical treatment in Norway has been penicillin G and an aminoglycoside, and this combination has been criticized over recent y. We wished to analyse the microbiological spectrum and susceptibility patterns of pathogens causing bacteraemia in febrile neutropenic patients. This was a prospective multicentre study. During the study period of 2 y, a total of 282 episodes of fever involving 243 neutropenic patients was observed. In 34% of episodes bacteraemia was documented. Overall, 40% of the episodes were caused by Gram-positive organisms, 41% by Gram-negative organisms and 19% were polymicrobial. The most frequently isolated bacteria were Escherichia coli (25.6%), a- and non-haemolytic streptococci (15.6%), coagulase-negative staphylococci (12.4%) and Klebsiella spp. (7.4%). None of the Gram-negative isolates was resistant to gentamicin, meropenem, ceftazidime or ciprofloxacin. Only 5 coagulase-negative staphylococci isolates were resistant to both penicillin G and aminoglycoside. The overall mortality rate was 7%, and 1.2% due to confirmed bacteraemic infection.

Adolescent↗

PubMed2005

Effects of some antibiotics on activity of glucose-6-phosphate dehydrogenase from human erythrocytes in vitro and effect of isepamicin sulfate on activities of antioxidant enzymes in rat erythrocytes.

The purpose of this study was to investigate effects of some antibiotics on glucose-6-phosphate dehydrogenase (G6PD), antioxidant enzymes, and malondialdehyde (MDA). Initially, for in vitro studies, G6PD was purified from human erythrocyte, 9811-fold in a yield of 42.4% by using ammonium sulfate precipitation and 2',5' ADP-Sepharose 4B affinity gel. The purified enzyme showed a single band on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The effects of four different antibiotics (isepamicin sulfate, meropenem, chloramphenicol, and thiamphenicol glisinat hydrochloride) were investigated on the purified enzyme. K(i) value and type of inhibition were determined by means of Lineweaver-Burk graphs and regression analysis graphs. Isepamicin sulfate inhibited the enzyme activity (I(50) value, 2.1 mM; K(i) value, 1.7 mM), whereas thiamphenicol glisinat hydrochloride activated the G6PD dose dependently. Other drugs showed no inhibition and activation effect. In addition, the effects of isepamicin sulfate on the activities of G6PD, glutathione reductase (GR), superoxide dismutases (SOD), glutathione peroxidase (GPx), catalase (CAT), and glutathione S-transferase (GST) and MDA concentrations were examined in Sprague-Dawley rat erythrocytes in vivo. A marked alteration in the activities of these enzymes and MDA levels may be the result of oxidative stress in the rats receiving isepamicin sulfate.

Adult↗

PubMed2001

Characterization of Pseudomonas aeruginosa isolates: occurrence rates, antimicrobial susceptibility patterns, and molecular typing in the global SENTRY Antimicrobial Surveillance Program, 1997-1999.

During 1997-1999, a total of 70,067 isolates (6631 Pseudomonas aeruginosa isolates) were analyzed in the SENTRY program by geographic region and body site of infection. The respiratory tract was the most common source of P. aeruginosa. P. aeruginosa isolation rates increased during the study interval. Europe was the only region to show a significant decline in beta-lactam and aminoglycoside susceptibility rates. There was a reduction in the rates of susceptibility of Canadian isolates to imipenem and of Latin American isolates to meropenem. A total of 218 multidrug-resistant P. aeruginosa isolates (MDR-PSA; resistant to piperacillin, ceftazidime, imipenem, and gentamicin) were observed; MDR-PSA occurrence rates (percentages of all isolates) ranged from 8.2% (Latin America) to 0.9% (Canada). No antimicrobial inhibited >50% of MDR-PSA strains. Molecular characterization of selected, generally resistant strains was performed. Isolates showing unique ribogroups were found in Europe, Latin America, and the United States, but clonal spread was documented in several medical centers.

Anti-Bacterial Agents↗

PubMed2001

Antifungal antibiotics and breakthrough bacteremias.

Patients with fever and neutropenia are at high risk for infection ( approximately 50%) and bacteremia ( approximately 20%). As a result, most are treated with antibacterial prophylaxis until their absolute neutrophil count exceeds 500 cells/mm(3) and their temperature returns to normal. The 1997 guidelines of the Infectious Diseases Society of America suggested 1 of 3 regimens: vancomycin plus ceftazidime, monotherapy with ceftazidime or imipenem (possibly cefepime or meropenem), or dual therapy with an aminoglycoside plus an antipseudomonal beta-lactam.

Antibiotic Prophylaxis↗

PubMed2001

National shortages of antimicrobial agents: results of 2 surveys from the Infectious Diseases Society of America Emerging Infections Network.

In November 1999 and August 2000, the Infectious Diseases Society of America Emerging Infections Network (EIN) surveyed its members about shortages of antimicrobial agents in their hospitals and medical centers. Almost 90% of the members had encountered shortages of 1 or more agents in 1999. Of 496 respondents, 382 (77%) reported diminished supplies of penicillin G. Other agents in short supply included meropenem (38%), ticarcillin with or without clavulanate (24%), cefazolin (20%), gentamicin (50%), and nafcillin-oxacillin (13%). In 2000, 291 (60%) of 485 respondents reported shortages of penicillin G, but significantly fewer members had experienced a lack of other agents. In both surveys, members indicated that shortages had affected numerous therapeutic indications. In 1999, members estimated that shortages had affected thousands of patients. In 2000, they estimated that fewer patients were affected. The results of these 2 EIN surveys raise questions about the forces that govern the availability of these valuable therapeutic resources.

Anti-Infective Agents↗

PubMed2002

Antibiotic-resistant gram-negative organisms in pediatric chronic-care facilities.

This study was designed to define the prevalence of colonization with antibiotic-resistant gram-negative rectal specimens were obtained from subjects residing in 2 pediatric extended-care facilities and were processed to identify gram-negative organisms resistant to ceftazidime, gentamicin, meropenem, and piperacillin-tazobactam. Horizontal transmission was assessed by analyzing all resistant isolates by pulsed-field gel electrophoresis. Forty percent of subjects were colonized with >/=1 resistant bacillus; >60% of organisms were resistant to >/=2 of the antibiotics tested. Colonization was disproportionate among residents with a tracheostomy or other prosthesis. More than 65% of colonized subjects shared 1 organism with another resident, with cross-colonization occurring among both enteric and nonenteric species. Children residing in chronic-care facilities represent a large reservoir for resistant bacilli. Such colonization may be amenable to simple barrier infection-control procedures.

Adolescent↗

PubMed2002

National survey on the susceptibility of Bacteroides Fragilis Group: report and analysis of trends for 1997-2000.

The results of a multicenter US survey using the National Committee for Clinical Laboratory Standards currently recommended methodology for measuring in vitro susceptibility of 2673 isolates of Bacteroides fragilis group species were compared from 1997 to 2000. The test panel consisted of 14 antibiotics: 3 carbapenems, 3 beta-lactam-beta-lactamase inhibitors, 3 cephamycins, 2 fluoroquinolones, clindamycin, chloramphenicol, and metronidazole. Declines in the geometric mean minimum inhibitory concentrations were seen with imipenem, meropenem, ampicillin-sulbactam, and the cephamycins. Increased geometric means were observed with the fluoroquinolones and were usually accompanied by an increase in resistance rates. Bacteroides distasonis shows the highest resistance rates among beta-lactam antibiotics, whereas Bacteroides vulgatus shows the highest resistance levels among fluoroquinolones. B. fragilis shows the lowest resistance rates for all antibiotics. All strains were susceptible to chloramphenicol and metronidazole concentrations <8 microgram/mL. The data underscore the need for species identification and continued surveillance to monitor resistance patterns.

Anti-Bacterial Agents↗

PubMed2005

Antibiotic dosing in critically ill adult patients receiving continuous renal replacement therapy.

Continuous renal replacement therapy (CRRT) is now commonly used as a means of support for critically ill patients with renal failure. No recent comprehensive guidelines exist that provide antibiotic dosing recommendations for adult patients receiving CRRT. Doses used in intermittent hemodialysis cannot be directly applied to these patients, and antibiotic pharmacokinetics are different than those in patients with normal renal function. We reviewed the literature for studies involving the following antibiotics frequently used to treat critically ill adult patients receiving CRRT: vancomycin, linezolid, daptomycin, meropenem, imipenem-cilastatin, nafcillin, ampicillin-sulbactam, piperacillin-tazobactam, ticarcillin-clavulanic acid, cefazolin, cefotaxime, ceftriaxone, ceftazidime, cefepime, aztreonam, ciprofloxacin, levofloxacin, moxifloxacin, clindamycin, colistin, amikacin, gentamicin, tobramycin, fluconazole, itraconazole, voriconazole, amphotericin B (deoxycholate and lipid formulations), and acyclovir. We used these data, as well as clinical experience, to make recommendations for antibiotic dosing in critically ill patients receiving CRRT.

Anti-Bacterial Agents↗