Avibactam Vs Carbapenems

In the last decade, the number of prescriptions for antibiotics has increases. Even though, antibiotics are helpful, an excess amount of antibiotics can be dangerous. Quite often antibiotics are wrongly prescribed to cure viruses when they are meant to target bacteria. Antibiotics are a type of medicine that is prone to kill microorganisms, or bacteria. By examining the PBS documentary Hunting the Nightmare Bacteria and the article “U.S. government taps GlaxoSmithKline for New Antibiotics” by Ben Hirschler as well as a few other articles can help depict the problem that is of doctors prescribing antibiotics wrongly or excessively, which can led to becoming harmful to the body.

According to a trial trying to determine bacterial resistance within the Enterobacteriaceae family “E. cloacae has been proven resistance to ampicillin, amoxicillin-clavulanic acid, first-generation cephalosporins, cephalothin, cefoxitin, broad-spectrum cephalosporins, as well as third generation cephalosporins.”1 The trial also stated that “this vast resistance is due to the bacteria’s

Widespread resistance to our arsenal of antibiotics is no longer a threat – it is reality. The emergence and spread of methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae and penicillin- and vancomycin-resistant enterococci coupled with a paucity of safe and effective agents for treatment of infections caused by these organisms threatens the transformative effect antibiotics have had on modern medicine. On 10 November 2015, the novel fifth generation cephalosporin ceftobiprole (Zevtera, Basilea Pharmaceutica) was registered in Australia for the treatment of both community- and hospital-acquired pneumonia in adults(1).

Due to this research being a retrospective chart review, confounding varables that can be seen as limitation to this study are inaccurate admission data and home medication documentation by clinical staff . Therefore, information that are missing from patients’ electronic record should be search for in the patient’s hard chart. Furthermore, the limitation of the sample size due to conducting the research in one hospital and the 30 days period after antibiotic therapy can be seen as a limitation of the study. In a study by Kavanagh et al. (2016), it was noted that patients that were exposed to high risk antimicrobials like Clindamycin, Cephalosporins, fluoroquinolones or Co-amoxiclav were at increased risk of

Klebsiella pneumoniae strains that were resistant to third-generation cephalosporins and amikacin were recovered from 62 of 395 patients (15.7%) during 1986. 25 isolates (40%) caused urinary tract infections. The outbreak involved three intensive care units (54 isolates), and spread from one unit to another and then to four wards (8 isolates). K pneumoniae of various serotypes and strains of different Enterobacteriaceae demonstrating the same antibiotic resistance pattern were isolated, which suggests dissemination of an R-factor. The isolates had low-level resistance to third-generation cephalosporins (mode minimum inhibitory concentration of cefotaxime, 2 mg/l) but remained sensitive to cephamycins. Cefotaxime was effective in cases of uncomplicated

Vancomycin is a glycopeptide, narrow spectrum, antibiotic that has been in clinical use for many years, and continues to be one of the most frequently prescribed antibiotic for the following conditions: Empiric therapy of gram-positive infections in high-risk patients , Empiric therapy of infections associated with central lines, hemodialysis shunts, vascular grafts or prosthetic heart valves, Documented or suspected MRSA or CONS , Patients who are allergic to beta-lactams and serious or life-threatening infections (e.g. endocarditis, meningitis, osteomyelitis). However, despite its clinical usefulness and established therapeutic benefits, therapeutic drug monitoring (TDM) is performed due to its high pharmacokinetic (PK) variability, age-dependent

B-lactam antibiotics, characterized by a four membered B-lactam ring, have treated infectious diseases since their discovery in 19281. B-lactam antibiotics currently occupy more than 65% of the world’s antibiotic market and consist of a variety of different drug classes such as penicillins, cephalosporins, carbapenems, and monobactams. They treat a variety of bacterial infections caused by bacterial organisms. The B-lactam antibiotics target bacteria, both Gram-positive and Gram-negative, by attacking the cell walls8 of bacterial enzymes, more commonly known as penicillin-binding proteins (PBPs), in a mecha-nism that is currently unknown. The ever-increasing inefficacy of B-lactams has led scientists to begin studying B-lactamases – the culprit

Cephalosporins, a betalactam antibiotic, are a widely used antibiotic. They are effective at penetrating deep into body fluids, especially with inflammation. Cephalosporins disrupt bacterial cell wall synthesis of the peptidoglycan layer. The first generation was effective against grampositive bacteria, while second generation against gramnegative.

Carbapenems are a class of beta-lactam antibiotics that are effective against many gram-positive, gram-negative, aerobic and anaerobic microorganisms (Holten and Onusko, 2000). Beta-lactam is a key component to the core structure of carbapenem which consists of 2-Azetidinone where two hydrogen atoms are substituted for two variable R groups (see Figure 1).

The introduction of different antimicrobials for treating different infections exhibited the importance of having antimicrobial susceptibility testing as a repetitive method in all microbiology laboratories. In laboratories this can be possible by using antibiotic disk that will diffuse gradually into the medium where the suspected organism is located. The fundamental principle of the antibiotic susceptibility testing was already being used in microbiology laboratories over 80 years. Several chemical agents like for example antiseptics, disinfectants, and antibiotics are engaged to fight the growth of microbes. Among these, antibiotics are commonly defined as the substances that microorganisms produce like Penicillium that can kill or inhibit the growth of other microorganisms, primarily bacteria. Antimicrobial susceptibility tests (ASTs) principally measures the capacity of an antibiotic or other antimicrobial agent to prevent microbial growth in vivo.

Ceftazidime-avibactam (Avycaz), is a cephalosporine combination antibiotic. It acts by inhibiting the bacteria’s cell wall synthesis, which causes the bacteria cell to lyse. The Avibactam portion of the drug, inactivates beta-lactamases and stops the breakdown of Ceftazidime (Drugs.com,2017c). The drug is widely distributed with small amounts crossing the blood brain barrier. It is not metabolized and is excreted by the kidneys. The onset of action is immediate and the half-life is greatly increased in patients with renal failure and dosage should be titrated based off the patient’s creatinine clearance (Drugs.com,2017c).

on inhibiting and treating pathogenic infections. Pathogenic infections are on the rise and cases are

Carbapenems are Beta lactam antibiotics used as a last resort in medical treatment against several bacterial infections as they possess the broadest spectrum of activity against various gram positive, gram negative and aerobic bacteria (Papp-Wallace et al. 2011). Originally developed from the carbapenem thienamycin which demonstrated the utmost antimicrobial activity, Carbapenems consist of six antibiotics: Doripenem, panipenem, biapenem, imipenem, meropenem and ertapenem all currently present in clinical use (Boromo et al 2011). Carbapenems all have a variety of vital roles in medicine and have helped reduce the threat of severe bacterial infections since the rise of multidrug-resistant pathogens. This can be seen with panipenem which is taken with betamipron to inhibit the uptake of panipenem into the renal tube of the kidney, proving effective in treating surgical and respiratory infections (Goa & Noble, 2003). Although Carbapenem has proved useful as a last resort of antibiotics, enterobacteriaceae a gram negative bacteria commonly consisting of Klebsiella and Escherichia species, has developed mechanisms of resistance to carbapenems (Duin and Perez 2015).These carbapenem resistant enterobacteriaceae (CRE) portray a new profound danger worldwide and require sustained efforts to control as there is little success on the elaboration of antibiotics to replace carbapenem and therefore limiting therapeutic options available to patients.

β-lactam antibiotics have continued to be the most popular drug for treating bacterial infections since its discovery in 1928 by Fleming and its introduction as an antibacterial agent in the early 1950.1 Most commonly used β-lactam drugs today stems from the original discovery and development of natural products from microorganisms like penicillin, cephalosporin and other β-lactam based antibiotics (Figure 1). 1,2 However, soon after its commercialization and widespread usage, β-lactamase secreting penicillin resistant strains of Staphylococcus aureus were isolated.3 The introduction of methicillin (a β-lactamase-insensitive semi-synthetic penicillin), to curb the resistance problem resulted in the evolution of another resistant strain known as methicillin-resistant Staphylococcus aureus (MRSA).4

Treatments that were provided during her stay were empiric intravenous vancomycin and piperacillin/tazobactam, along with oral fluconazole, which was added due to oral candidiasis. Azithromycin 1200mg weekly was added for MAC prophylaxis and since she was at a lower risk for the nosocomial pathogens, the antibiotics given were reduced to amoxicillin instead.