Faropenem: review of a new oral penem

Faropenem medoxomil is a new orally administered penem antibiotic. Its chiral tetrahydrofuran substituent at position C2 is responsible for its improved chemical stability and reduced CNS effects, compared with imipenem. Faropenem demonstrates broad-spectrum in vitro antimicrobial activity against many Gram-positive and -negative aerobes and anaerobes, and is resistant to hydrolysis by nearly all beta-lactamases, including extended-spectrum beta-lactamases and AmpC beta-lactamases. However, faropenem is not active against methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, Pseudomonas aeruginosa or Stenotrophomonas maltophilia. Prospective, multicenter, randomized, double-blind, comparative (not vs placebo) clinical trials of acute bacterial sinusitis (ABS), acute exacerbations of chronic bronchitis (AECB), community-acquired pneumonia (CAP) and uncomplicated skin and skin structure infections (uSSSIs) have demonstrated that faropenem medoxomil has equivalent efficacy and safety compared with cefuroxime, clarithromycin, azithromycin, amoxicillin, cefpodoxime and amoxicillin-clavulanate. The evidence supports faropenem medoxomil as a promising new oral beta-lactam with proven efficacy and safety for the treatment of a variety of community-acquired infections. However, the US FDA recently rejected faropenem for all four indications stating that the clinical trials in ABS and AECB should have been performed versus a placebo. In the CAP studies, the FDA stated that they could not be certain of the validity of the study population actually having the disease and for uSSSI, the FDA stated that only a single trial was not adequate evidence of efficacy for this indication.     

Faropenem medoxomil: a treatment option in acute bacterial rhinosinusitis

Faropenem medoxomil is the first oral penem in a new class of beta-lactam antibiotics. Faropenem medoxomil has excellent in vitro activity against Streptococcus pneumoniae, Haemophilus influenzae and other key pathogens implicated in acute bacterial rhinosinusitis. Clinical studies have demonstrated that, in the treatment of acute bacterial rhinosinusitis in adults, 7 days of treatment with faropenem medoxomil is as clinically and bacteriologically effective as 10 days of treatment with cefuroxime axetil. One study showed faropenem medoxomil to be superior to cefuroxime axetil. Overall, the safety profile of faropenem medoxomil is similar to that of most comparators. Specifically, the minimal impact of faropenem medoxomil on the gastrointestinal flora leads to less diarrhea and other adverse events than coamoxicillin-clavulanate. Faropenem medoxomil has almost no drug-drug interactions and little requirement for dosage adjustments in the typical acute rhinosinusitis population.     

Haemophilus influenzae in respiratory tract infections in community-based clinical practice: therapy with gatifloxacin

In this community-based safety surveillance study, the advanced-generation fluoroquinolone gatifloxacin was administered empirically to 15625 adults with community-acquired respiratory tract infections (RTIs), including 1562 clinically evaluable patients with community-acquired pneumonia (CAP) and 2391 with acute exacerbations of chronic bronchitis (AECB). Haemophilus influenzae was the most common pathogen isolated in AECB (40.1%) and the second most common in CAP (36.8%). In vitro susceptibility to gatifloxacin and other fluoroquinolones, amoxicillin/clavulanate, ceftriaxone, cefuroxime axetil, tetracycline, and azithromycin ranged from 95.8% to 100%. In comparison, a significant percentage of the isolates were not susceptible to clarithromycin ( approximately 41%), ampicillin (22% to 28%), and trimethoprim/sulfamethoxazole (14% to 18%). The susceptibility pattern was generally independent of exposure to another antimicrobial in the previous 30 days. CAP and AECB patients infected with H. influenzae had signs and symptoms similar to those infected with Streptococcus pneumoniae. Among clinically evaluable patients with H. influenzae, gatifloxacin cured 159 of 166 (95.8%) with AECB and 112 of 118 (94.9%) with CAP. The cure rate was independent of the beta-lactamase status or serotype of the H. influenzae strain. H. influenzae is not a more benign pathogen in community-acquired RTIs but causes signs and symptoms that are indistinguishable from those caused by other pathogens, notably S. pneumoniae.     

Ertapenem: review of a new carbapenem

The carbapenems are β-lactam-type antibiotics with an exceptionally broad spectrum of activity. Ertapenem is a new carbapenem developed to address the pharmacokinetic shortcomings (short half-life) of imipenem and meropenem. Ertapenem shares similar structural features with meropenem, including its stability to dehydropeptidase-1, allowing it to be administered without a dehydropeptidase-1 inhibitor. Ertapenem, like imipenem and meropenem, demonstrates broad-spectrum antimicrobial activity against many Gram-positive and -negative aerobes and anaerobes and is resistant to nearly all β-lactamases, including extended-spectrum β-lactamases and AmpCs. However, it differs from both imipenem and meropenem in demonstrating limited activity against Enterococcus spp., Pseudomonas aeruginosa and other nonfermentative Gram-negative bacteria commonly associated with nosocomial infections. The extensive protein binding of ertapenem extends the half-life and allows for once-daily dosing. Prospective, multicenter, randomized, double-blind, comparative clinical studies demonstrate similar clinical efficacy of ertapenem compared with other agents. Clinical trials of complicated intra-abdominal infection, acute pelvic infection, complicated skin and soft-structure infection, community-acquired pneumonia and complicated urinary tract infections demonstrated that ertapenem has equivalent efficacy and safety compared with ceftriaxone and piperacillin/tazobactam. Ertapenem is a promising new carbapenem with excellent efficacy and safety for the treatment of a variety of community-acquired infections. It also appears to be of great value as an outpatient parenteral antimicrobial therapy.     

Multicenter evaluation of the efficacy and safety of gatifloxacin in Mexican adult outpatients with respiratory tract infections

Respiratory tract infections (RTIs), the most common indication for outpatient antimicrobial therapy, impose a heavy medical and societal burden and present a difficult therapeutic challenge in the face of increasing pathogen resistance worldwide. Gatifloxacin is a new broad-spectrum fluoroquinolone with excellent activity against prevalent respiratory bacteria, including penicillin-resistantStreptococcus pneumoniae and atypical pathogens. A multicenter, open-label, noncomparative surveillance study carried out in Mexico evaluated the safety and efficacy of oral gatifloxacin 400 mg once daily in 17,923 adult outpatients with community-acquired pneumonia (CAP) (n=3322), acute exacerbations of chronic bronchitis (AECB) (n=5885), and acute bacterial sinusitis (n=8716). Voluntary, unpaid physician participation contributed to an unbiased study design. Physician-assessed global rate of cure or improvement was 96.3%; efficacy was 95.8% in CAP, 96.1% in AECB, and 96.4% in sinusitis. The incidences of relapse (1.5%) and therapeutic failure (0.7%) were low. The most commonly reported adverse events, nausea (2.76%), headache (2.20%), and dizziness (1.33%), were generally mild and self-limited. Oral gatifloxacin 400 mg once daily is effective and safe for patients with CAP, AECB, and acute sinusitis.     

Ceftaroline fosamil for treatment of communityacquired pneumonia: findings from FOCUS 1 and 2 and potential role in therapy

Cephalosporins have been widely used over the last few decades (often as first-line antibiotic therapy) for numerous infections, owing primarily to their broad spectrum of microbiologic activity and favorable safety profile. Current Infectious Diseases Society of America guidelines identify a third-generation cephalosporin in combination with a macrolide antibiotic as an option for treatment of hospitalized adult patients with community-acquired pneumonia (CAP) outside the intensive care unit setting. Although ceftriaxone is a frequently used agent for CAP, increasing incidence of multidrug-resistant Streptococcus pneumoniae and concerns regarding poor outcomes associated with ineffective therapy have prompted the search for a well-tolerated treatment alternative that is effective against bacteria that can cause CAP. Ceftaroline fosamil, the prodrug of ceftaroline, is a new extended-spectrum cephalosporin that exhibits time-dependant bactericidal activity against numerous Gram-negative and Gram-positive organisms, including methicillin-resistant Staphylococcus aureus and penicillin-resistant S. pneumoniae. Notable exceptions include Pseudomonas spp. and Gram-negative organisms that produce extended-spectrum β-lactamases or carbapenemases. Two large Phase III clinical trials (FOCUS 1 and 2) reported that ceftaroline fosamil was well tolerated, with a clinical cure rate of CAP that was noninferior to that with ceftriaxone in nonintensive care unit adult inpatients with moderately severe (Pneumonia Outcomes Research Team score of III or IV) community-acquired pneumonia.     

Effect of protein binding on the in vitro activity and pharmacodynamics of faropenem

The influence of protein binding upon different aspects of the in vitro activity of faropenem on recently isolated Staphylococcus aureus and respiratory pathogens was determined. The protein binding of faropenem was investigated in inactivated human serum and albumin by ultrafiltration. The effect of the presence of inactivated human serum and albumin on the in vitro activity of faropenem and amoxicillin was established and the influence of protein binding on the pharmacodynamic properties of faropenem and amoxicillin was compared. The protein binding of faropenem was 96% and 95% in pooled inactivated human serum and 99% and 98% in 45 mg/L human albumin, at 8 and 25 mg/L, respectively. The presence of inactivated human serum (20% and 70%) increased the mean faropenem MICs by two dilution steps and albumin increased the mean faropenem MICs by three dilution steps. The mean amoxicillin MICs were less affected than faropenem by the presence of either inactivated human serum or albumin. Faropenem and amoxicillin exhibited similar time-dependent kinetics. Faropenem was bacteriostatic on Moraxella catarrhalis, Haemophilus influenzae and group A streptococci, and bactericidal for Streptococcus pneumoniae (after 4 h with concentrations equivalent to 5 x and 10 x MIC) in Iso-Sensitest broth. In 70% inactivated human serum faropenem was slowly bactericidal against M. catarrhalis, H. influenzae (one strain) and S. pneumoniae (one strain) but not group A streptococci and the other S. pneumoniae strain. A significant inoculum effect was observed with all strains except S. pneumoniae. Both faropenem and amoxicillin appeared more active in 70% inactivated human serum than in Iso-Sensitest broth.     

Telithromycin: the first ketolide antimicrobial

BACKGROUND: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration (FDA) approval for clinical use. It is approved for the treatment of community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB), and acute maxillary sinusitis (AMS) in adults. OBJECTIVE: This article reviews the mechanism of action, in vitro antimicrobial activity, pharmacokinetics and pharmacodynamics, clinical efficacy, safety, and drug-interaction profile of telithromycin. METHODS: Relevant studies were identified through a search of the English-language literature indexed on MEDLINE (1990-March 2005) using the terms telithromycin and HMR 3647, a review of the reference lists of identified articles, and a review of the briefing document prepared by the manufacturer of telithromycin for presentation to the FDA Anti-infective Drugs Advisory Committee. A search of abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy (2001-2004) also was performed. RESULTS: The results of in vitro susceptibility studies suggest that telithromycin provides coverage against the key respiratory pathogens, both typical and atypical. In addition, telithromycin may be useful against multidrug-resistant strains of Streptococcus pneumoniae and against Haemophilus influenzae, irrespective of beta-lactamase production. In randomized, double-blind, comparative trials (against amoxicillin, amoxicillin/clavulanate, cefuroxime axetil, clarithromycin, moxifloxacin, or trovafloxacin), telithromycin had comparable efficacy to its comparators in the empiric treatment of CAP (4 studies), AECB (3 studies), and AMS (3 studies). Telithromycin is dosed at 800 mg (two 400-mg tablets) QD in community-acquired respiratory tract infections (RTIs). No dose adjustment is required in the elderly, patients with mild to moderate renal insufficiency, or patients with hepatic insufficiency. The majority of adverse events associated with telithromycin were mild to moderate, with gastrointestinal effects (diarrhea, nausea, vomiting) being the most commonly reported, followed by headache and dizziness. Telithromycin has been associated with elevations in hepatic transaminases and prolongation of the electrocardiographic QTc interval, although the significance of these findings is not known. Telithromycin is also a strong inhibitor of and substrate for the cytochrome P450 (CYP) 3A4 isozyme. Therefore, it is important to monitor for potential drug interactions with medications that prolong the QTc interval or are metabolized by the CYP system. CONCLUSIONS: Telithromycin appears to be a useful option for the empiric treatment of community-acquired RTIs in adults. It may be particularly useful in the outpatient setting in areas with high rates of penicillin- and macrolide-resistant S pneumoniae; it may also be an alternative agent for patients who are allergic to beta-lactams and live in areas with a high prevalence of multidrug-resistant S pneumoniae or for those who have failed to respond to beta-lactam- or macrolide-based therapy.     

Extended release amoxicillin/clavulanate: optimizing a product for respiratory infections based on pharmacodynamic principles

Acute bacterial respiratory tract infections cause a great deal of human morbidity and mortality. Treatment guidelines for these infections include macrolides, doxycycline, β-lactams and β-lactam/β-lactamase inhibitor combinations such as amoxicillin/clavulanic acid to provide coverage for the common respiratory pathogens, including penicillin and macrolide nonsusceptible Streptococcus pneumoniae, as well as β-lactamase-producing Haemophilus influenzae and Moraxella catarrhalis. In response to recent guidelines recommending higher dose amoxicillin to extend coverage to a higher percentage of S. pneumoniae, a new formulation of amoxicillin/clavulanic acid was developed. This formulation includes a higher amoxicillin dose, with part of the amoxicillin dose being in an extended release formulation, without increasing the clavulanate dose, for twice-daily oral treatment of these infections. Clinical studies of community-acquired pneumonia and acute rhinosinusitis have shown that the new formulation is well tolerated and highly efficacious, with clinical outcomes equivalent to comparators.     

Activities of Faropenem, an Oral β-Lactam, against Recent U.S. Isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis

The in vitro activities of faropenem and other antimicrobial agents were determined against 4,725 Streptococcus pneumoniae isolates, 2,614 Haemophilus influenzae isolates, and 1,193 Moraxella catarrhalis isolates collected from 273 U.S. laboratories during 1999. Faropenem MICs at which 90% of isolates are inhibited were 0.008, 0.25, and 1 microg/ml for penicillin-susceptible, -intermediate, and -resistant S. pneumoniae strains, respectively; 0.5 and 1 microg/ml for beta-lactamase-positive and -negative H. influenzae strains, respectively; and 0.12 and 0.5 microg/ml for beta-lactamase-negative and -positive M. catarrhalis strains, respectively. Faropenem holds promise as an oral therapy for community-acquired respiratory tract infections.     

Gatifloxacin in community-based treatment of acute respiratory tract infections in the elderly

The elderly are at increased risk for respiratory tract infections. To evaluate the safety and efficacy of gatifloxacin in adults of any age with community-acquired respiratory tract infections, this open-label, multicenter, noncomparative study in community-based practices enrolled male and female outpatients at least 18 years old with a clinical diagnosis of community-acquired pneumonia (CAP), acute-bacterial exacerbation of chronic bronchitis (AECB), or acute uncomplicated maxillary sinusitis. Gatifloxacin 400 mg was administered once daily for seven to 14 days. Of 14781 clinically evaluable patients, 2505 were at least 65 years old, 499, at lest 80. Cure rates for CAP, AECB, and sinusitis ranged from 91.6% to 95.5% for patients less than 65 years old, 91.1% to 96.2% for those 65 to 79 years of age, and 89.5% to 94.8% for those at least 80 years old. Each age group, including patients with concomitant cardiovascular or diabetic conditions, tolerated treatment well. Gatifloxacin is efficacious and well tolerated in adult outpatients of any age with respiratory tract infections and is an important therapeutic option, particularly in communities with a high prevalence of resistant pathogens.     

Antibacterial activity of telithromycin and comparators against pathogens isolated from patients with community-acquired respiratory tract infections: the Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin study year 5 (2003–2004)

The activity of telithromycin and comparator antibacterials was examined in isolates of Streptococcus pneumoniae and Haemophilus influenzae isolated from patients with community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB), or sinusitis during year 5 (2003–2004) of the Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin global resistance surveillance study. Among S. pneumoniae, penicillin nonsusceptibility and erythromycin resistance were 35.7% and 36.0%, respectively. β-Lactamase was produced by 12.3% of H. influenzae isolates. β-Lactamase–negative ampicillin-resistant strains, mainly from Japan, comprised 5.2% of global H. influenzae isolates. Telithromycin and levofloxacin were the most active agents tested against S. pneumoniae and H. influenzae (>99% of isolates susceptible) isolated from patients with CAP, AECB, or bacterial sinusitis. Amoxicillin–clavulanate, levofloxacin, and telithromycin were the most active agents against multidrug-resistant S. pneumoniae.     

Faropenem enhances superoxide anion production by human neutrophils in vitro.

Neutrophils are important cellular components in the defence against infections and many studies in vitro have shown that some antibiotics affect neutrophil function. We examined the effect of faropenem, a new oral penem antibiotic on neutrophil killing function by determining the generation of superoxide anion in vitro. The production of superoxide anion was measured by chemiluminescence amplified by a Cypridina luciferin analogue in the presence of N-formyl-Met-Leu-Phe (fMLP). Faropenem significantly enhanced chemiluminescence in a dose-dependent manner. The effect of faropenem was maximal at 5 min of incubation time and continued for at least 30 min. The effect of faropenem was also observed when neutrophils were stimulated by a calcium ionophore (ionomycin), while the effect of faropenem did not change in the presence of 12-O-tetra-decanoylphorbolmyristate acetate. Cytosol Ca2+ concentration ([Ca2+]i) monitored with Fura-2 increased in response to fMLP, however, faropenem did not influence the response of [Ca2+]i to fMLP. Our results suggest that faropenem enhanced the generation of superoxide anion by neutrophils, probably at the site where cytosol Ca2+ regulates NADPH oxidase. Faropenem might be potentially advantageous in the treatment of infections because a synergic interaction of antibodies and cytocidal neutrophils is necessary for the early eradication of the pathogenic bacteria.     

Faropenem,a new oral penem: antibacterial activity against selected anaerobic and fastidious periodontal isolates

The in vitro activity of faropenem, an oral penem, was compared with those of penicillin, co-amoxiclav, cefoxitin, clindamycin, erythromycin and metronidazole against 106 isolates of anaerobic pathogens involved in systemic infections. The organisms tested comprised Porphyromonas gingivalis (29), Prevotella spp. (eight), Prevotella melaninogenica (seven), Prevotella intermedia (five), Actinomyces spp. (25), Fusobacterium nucleatum (14), Peptostreptococcus spp. (11), Bacteroides ureolyticus (five) and Bacteroides forsythus (two). The antimicrobial properties of faropenem were investigated by studying MICs, MBCs, time-kill kinetics and post-antibiotic effect (PAE). Faropenem was highly active against all the anaerobes tested (MIC(90) < or = 0.5 mg/L) and was bactericidal against both beta-lactamase-positive and -negative anaerobes, with a maximum bactericidal effect at 10 x MIC at between 12 and 24 h. In addition, faropenem had an in vitro PAE on all the tested isolates and this was not influenced by beta-lactamase production. Faropenem may be useful for treating infections caused by periodontal bacteria or oral flora.     

Levofloxacin in the treatment of community-acquired pneumonia

Levofloxacin is a fluoroquinolone that has a broad spectrum of activity against several causative bacterial pathogens of community-acquired pneumonia (CAP). The efficacy and tolerability of levofloxacin 500 mg once daily for 10 days in patients with CAP are well established. Furthermore, a high-dose (750 mg), short-course (5 days) of once-daily levofloxacin has been approved for use in the USA in the treatment of CAP, acute bacterial sinusitis, acute pyelonephritis and complicated urinary tract infections. Levofloxacin can be used as a monotherapy in patients with CAP, however, levofloxacin combination therapy with anti-pseudomonal β-lactam (or aminoglycoside) should be considered if Pseudomonas aeruginosa is the causative pathogen of the respiratory infection. The high-dose, short-course levofloxacin regimen maximizes its concentration-dependent antibacterial activity, decreases the potential for drug resistance and has better patient compliance. Oral levofloxacin is rapidly absorbed and is bioequivalent to the intravenous formulation and the patients can switch between these formulations, which results in more options with respect to the therapeutic regimens. Furthermore, levofloxacin is generally well tolerated, has good tissue penetration and adequate concentrations can be maintained at the site of infections.     

Community-acquired lower respiratory tract infections: clinical experience with beta-lactam/beta-lactamase inhibitors

Once universally susceptible to aminopenicillins and cephalosporins, an increasing percentage of the common respiratory pathogens that cause community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECB) are now resistant to these agents and exhibit cross-resistance to other commonly used antibiotics. In an era of multidrug resistance, guidelines for the management of both CAP and AECB can help to guide appropriate antibiotic prescribing, encourage the rational use of antibiotics, which will help to limit the emergence of resistance, and conserve the use of new antimicrobial agents for more serious infections. Central to all current management guidelines is risk assessment, which includes an appreciation of local antibiotic resistance patterns. beta-Lactam antibiotics are still considered among the drugs of choice for the treatment of CAP and AECB, although their use can be compromised by high rates of resistance. The beta-lactam/beta-lactamase inhibitor combinations, such as ampicillin/sulbactam, provide a means of overcoming such resistance and represent a suitable alternative.     

Combinations of Orally Administered β-Lactams to Maximize Spectrum and Activity against Drug-resistant Respiratory Tract Pathogens: I. Synergy Studies of Amoxicillin and Cefixime with Streptococcus pneumoniae

Streptococcus pneumoniae strains have emerged that are resistant to penicillin (MICs >0.06 μg/mL) and many other β-lactams. However, some older compounds such as amoxicillin have potency against these pneumococci with altered penicillin-binding proteins, but are labile to β-lactamases produced by other prevalent respiratory tract pathogens. The interactions of amoxicillin with an enzyme-stable cephalosporin (cefixime) with a long elimination half-life were examined by the checkerboard dilution method versus 39 S. pneumoniae strains (13 resistant, 15 intermediate, and 11 susceptible to penicillin). Among 24 strains with evaluable drug interaction tests, 17 (71%) demonstrated partial or complete synergy. This favorable interaction produces a cefixime susceptibility category change from resistant or intermediate to susceptible for 16 of 28 strains (57%), when combined with ≤1 μg/mL amoxicillin. Thus, the use of two currently available oral β-lactams (amoxicillin twice a day + cefixime once a day; three total doses) appears to be a potential alternative treatment with greater spectrum for community-acquired respiratory tract infections pending clinical trial results.     

New insights in the treatment by levofloxacin

Levofloxacin is widely regarded as one of the most important fluoroquinolones available today. It possesses excellent activity against a wide range of important pathogens, including those resistant to many other antimicrobials. While rates of resistance to other previously useful antimicrobial classes has grown, levofloxacin has maintained its efficacy, with generally very low rates of resistance around the world. It is indicated for a wide range of infections including community-acquired respiratory infections in adults, particularly community-acquired pneumonia (CAP), acute bacterial exacerbations of chronic bronchitis (AECB), and acute sinusitis. In addition, it is recommended for infections of skin and soft tissue, and the urinary tract. With postmarketing surveillance data available for the last decade, levofloxacin possesses an unparalleled database to demonstrate its clinical efficacy and safety. Remarkably, levofloxacin continues to expand its list of indications. The development of a new high-dose 750-mg schedule has the potential to decrease the duration of treatment as well as reduce the emergence of resistance.     

Multiresistant Enterobacteriaceae: new threat of an old problem

The Enterobacteriaceae are among the most important causes of serious nosocomial and community-onset bacterial infections in humans, and resistance to antimicrobial agents in these species has become an increasingly relevant problem for healthcare providers. β-lactam and fluoroquinolone antibiotics are important drug classes used to treat infections caused by Enterobacteriaceae. Emerging resistance mechanisms against these agents have recently been described in Enterobacteriaceae and include the production of newer β-lactamases and plasmid-mediated quinolone resistance. The newer β-lactamases consist of the following: plasmid-mediated AmpC β-lactamases (e.g., ephamycin [CMY], CMY types), extended-spectrum β-lactamases (e.g., cefotaxime [CTX], CTX-M first isolated at Munich) and carbapenem-hydrolyzing enzymes (e.g., Klebsiella pneumoniae carbapenemase [KPC], KPC types and the metallo-β-lactamases). Recent developments in the epidemiology, clinical relevance and laboratory detection of infections caused by multiresistant Enterobacteriaceae with these new types of resistance mechanisms will be addressed in this review.     

Clinical significance of extended-spectrum β-lactamases

The spread of extended-spectrum β-lactamases (ESBLs) in nosocomial and community-acquired enterobacteria is an important challenge for clinicians as the therapeutic options for these organisms are limited. The emergence of ESBL-producing Escherichia coli in the community, associated with the spread of CTX-M ESBL, is one of the most significant epidemiologic changes in infectious diseases during recent years. The epidemiology of these infections is complex and combines the expansion of mobile genetic elements with clonal spread. Infections caused by ESBL producers are associated with increased mortality, length of stay and increased cost. An inadequate empirical therapy for serious infections caused by these organisms is independently associated with increased mortality. Carbapenems are the drugs of choice for serious infections caused by ESBL-producing organisms but their overuse is a cause of concern.