What do carbapenems not cover?
Carbapenems do not have activity against Enterococcus faecium , Methicillin-resistant Staphylococcus aureus (MRSA) or Stenotrophom*onas maltophilia . Biapenem shows greater activity against Enterobacteriaceae than imipenem and two-fold more potency against P. aeruginosa .
Carbapenems also have good activity against most Gram-negative bacteria, including Enterobacter, E. coli, Morganella morganii, and Klebsiella. For the very resistant P. aeruginosa, doripenem and meropenem are highly potent because they require multiple drug resistance pathways.
Carbapenems (imipenem, meropenem, doripenem) possess broad-spectrum in vitro activity, which includes activity against many Gram-positive, Gram-negative and anaerobic bacteria; carbapenems lack activity against Enterococcus faecium, methicillin-resistant Staphylococcus aureus and Stenotrophom*onas maltophilia.
Carbapenems, among the beta-lactams, are the most effective against Gram-positive and Gram-negative bacteria presenting a broad spectrum of antibacterial activity. Their unique molecular structure is due to the presence of a carbapenem together with the beta-lactam ring.
Comparison of the 3 broadest spectrum beta-lactams: Cefepime, Zosyn, and Carbapenems (non-Ertapenem) have activity against both Gram positive (MSSA, Strep) and Gram negative including Pseudomonas. They do NOT cover: MRSA, VRE, Atypicals, among others.
Meropenem is active against methicillin-susceptible S. aureus and most strains of methicillin-susceptible coagulase-negative staphylococci. However, as with other carbapenems, meropenem has poor activity against MRSA and methicillin-resistant coagulase-negative staphylococci.
The carbapenem class of antibiotics includes meropenem, imipenem, ertapenem, and doripenem. These antibiotics are often used as the last line of treatment for infections caused by resistant Gram-negative bacteria including Pseudomonas aeruginosa.
coli. Carbapenem-hydrolyzing enzymes are β-lactamases that significantly hydrolyze imipenem, meropenem, and ertapenem and, usually, a wide range of other β-lactam antibiotics. Carbapenem resistance has been rarely reported in E. coli.
Generally speaking, carbapenems enter Gram-negative bacteria through outer membrane proteins (OMPs), also known as porins.
Although carbapenems are not first-choice drugs for the treatment of Salmonella infections, the emergence of such resistance in zoonotic pathogens poses a pressing threat to public health, as they may be transferred to humans through the food chain.
Which antibiotics cover Gram-negative and gram-positive?
Penicillin, tetracycline and erythromycin are broad-spectrum drugs, effective against gram-positive and gram-negative microorganisms.
Meropenem readily penetrates the cell wall of most Gram-positive and Gram-negative bacteria to reach penicillin-binding- protein (PBP) targets. Its strongest affinities are toward PBPs 2, 3 and 4 of Escherichia coli and Pseudomonas aeruginosa; and PBPs 1, 2 and 4 of Staphylococcus aureus.
Many antibiotics, such as vancomycin, which like β-lactam antibiotics targets the cell wall peptidoglycan, are ineffective against Gram-negative bacteria, simply because they have chemical properties that do not allow them to utilize these pathways to effectively penetrate the outer membrane.
Some Klebsiella bacteria have become highly resistant to antibiotics. When bacteria such as Klebsiella pneumoniae produce an enzyme known as a carbapenemase (referred to as KPC-producing organisms), then the class of antibiotics called carbapenems will not work to kill the bacteria and treat the infection.
Ertapenem is not as active against Pseudomonas aeruginosa as other carbapenems. It is also active against most gram-positive bacteria, except methicillin-resistant strains of Staphylococcus and Enterococcus.
Acinetobacter is already resistant to many antibiotics. Resistance to carbapenems further reduces patient treatment options.
Carbapenems do not have activity against Enterococcus faecium , Methicillin-resistant Staphylococcus aureus (MRSA) or Stenotrophom*onas maltophilia .
Gram-positive bacteria susceptible (MIC90 ≤4 mg/L) to meropenem include methicillin-sensitive Staphylococcus aureus and S. epidermidis, and Streptococcus pneumoniae.
Pseudomonas infection can be treated with a combination of an antipseudomonal beta-lactam (eg, penicillin or cephalosporin) and an aminoglycoside. Carbapenems (eg, imipenem, meropenem) with antipseudomonal quinolones may be used in conjunction with an aminoglycoside.
Meropenem plus Ceftaroline Is Active against Enterococcus faecalis in an In Vitro Pharmacodynamic Model Using Humanized Dosing Simulations | Antimicrobial Agents and Chemotherapy.
Does meropenem cover MRSA?
Pathogens resistant to meropenem are Stenotrophom*onas, MRSA, E. faecium, approximately 10 percent of Pseudomonas strains, and most strains of penicillin- and cefotaxime-nonsusceptible S. pneumoniae.
** Ceftaroline (5th Gen) does NOT cover Pseudomonas.
Meropenem therapy in critically ill patients could be optimized for K. pneumoniae isolates with an MIC of ≤2 mg/liter by using a continuous infusion in settings with more than 50% isolates have a MIC of ≥32mg/L.
Somewhat paradoxically, meropenem (MEM) is almost invariably included in such combinations, since the above cited studies showed that high-dose MEM was able to improve survival from KPC-Kp severe infections, despite in vitro nonsusceptibility (minimum inhibitory concentration [MIC] > 2 mg/L).
The carbapenems (imipenem, meropenem, ertapenem, doripenem) are still the first choice of treatment for serious infections with ESBL-producing E. coli and K. pneumoniae.
Carbapenems do NOT have activity against methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecium, Stenotrophom*onas maltophilia, or atypical organisms (Chlamydia/Chlamydophila spp, Legionella spp, Mycoplasma spp).
Data from a phase 3 clinical trial published yesterday in the New England Journal of Medicine indicate that an oral carbapenem antibiotic may be an option for treating complicated urinary tract infections (cUTIs) caused by multidrug-resistant bacteria.
The broad antimicrobial spectrum and the pharmacological profiles of the carbapenems are useful in the treatment of complicated UTIs, especially of febrile complicated UTIs. Carbapenems are superior to cephalosporins or penicillins in Gram-negative bacteria including class C β-lactamase and ESBL producers.
Penicillin, cloxacillin, and erythromycin should be enough to cover 90 per cent of Gram-positive infections.
Antibiotics for gram-positive bacterial infections. Vancomycin, teicoplanin, quinupristin/dalfopristin, and linezolid.
Which antibiotic is sensitive to Gram-positive?
Linezolid and vancomycin are active against the most serious gram-positive bacteria, including streptococci, vancomycin-resistant enterococci (VRE) and MRSA [38].
Pseudomonas aeruginosa
aeruginosa can become resistant to meropenem by upregulation of efflux pumps [17]. In the US, 10%–20% of P. aeruginosa clinical isolates identified in healthcare settings are resistant to at least 1 carbapenem [18, 19].
coli strains were screened from 1014 isolates. We found that they were all resistant to meropenem and imipenem. Amikacin showed the best sensitivity, with gentamicin coming up next. The positive rate of blaNDM was 80% (4/5).
Monotherapy for urosepsis due to aerobic gram-negative bacilli may include aztreonam, levofloxacin, a third- or fourth-generation cephalosporin, or an aminoglycoside. However, preferred monotherapy for enterococcal urosepsis involves ampicillin or vancomycin.
- azithromycin.
- clarithromycin.
- amoxicillin + clavulanate.
- second or third generation cephalosporin.
- co-trimoxazole 10mg/kg of sulphamethoxazole.
Example: Gram-negative bacteria have an outer layer (membrane) that protects them from their environment. These bacteria can use this membrane to selectively keep antibiotic drugs from entering.
Enterobacterales that are resistant to carbapenems by any mechanism are called carbapenem-resistant Enterobacterales (CRE) (those that produce carbapenemases are called 'carbapenemase-producing Enterobacteriaceae' (CP-CRE, or CPE for short)) and Enterobacteriaceae that produce ESBL enzymes are called 'ESBLs'.
The current components of an effective combination regimen recommended for treatment of CR-KP include high-dose carbapenem therapy administered by extended infusion (e.g., meropenem), which is combined with colistin and/or tigecycline, gentamicin or fosfomycin if susceptibility can be demonstrated.
Bacteria have acquired multiple mechanisms of resistance including enzymatic inactivation, target site mutation and efflux pumps. Of these, the development and emergence of inactivating enzymes were established early following the discovery and clinical introduction of the β-lactam class of antibiotics.
Several in vitro studies have evaluated ertapenem and have shown excellent in vitro susceptibility to ESBL-producing Escherichia coli and Klebsiella pneumoniae with comparable MIC 90 to that of group 2 carbapenems.
Can E coli be resistant to ertapenem?
The E. coli CO strain was resistant to extended-spectrum cephalosporins, cefoxitin, and moxalactam. In addition, it was intermediately susceptible to imipenem and meropenem (MIC 8 mg/L each) and was resistant to ertapenem (MIC >256 mg/L) (Table).
Cefazolin and Ertapenem, a Synergistic Combination Used To Clear Persistent Staphylococcus aureus Bacteremia. Antimicrob Agents Chemother.
Imipenem is usually active against K. pneumoniae that produce extended-spectrum β-lactamases, including porin-deficient variants. It is also active against isolates producing plasmid-mediated AmpC-type β-lactamases.
Meropenem-clavulanate is effective against extensively drug-resistant Mycobacterium tuberculosis.
Carbapenems are a class of very effective antibiotic agents most commonly used for the treatment of severe bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections.
Carbapenems may therefore be used as the first choice of antibiotics in the treatment of febrile complicated UTIs, even if there is polymicrobial infection caused by P. aeruginosa and E. faecalis.
