Avibactam: Mechanism of Action, Adverse Effects, and Specificity

This report provides a detailed analysis of Avibactam, a non-beta lactam beta-lactamase inhibitor. The report explores the drug's mechanism of action, highlighting its role in inhibiting serine beta-lactamase enzymes and its interaction with beta-lactam antibiotics like penicillin and cephalosporin, thus preventing bacterial cell wall synthesis. It also discusses the drug's specificity, targeting a wide range of bacteria, particularly those with multi-drug resistance, including Enterobacteriaceae and Pseudomonas species. The report also examines the adverse effects associated with Avibactam, including headaches, nausea, and potential disruption of the gut microbiota. The report also includes a figure illustrating the mechanism of action and references supporting the information presented.

Running head: AVIBACTAM
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Drug Target and Chemical Interaction:
The avibactam drugs are known as the non-beta lactam beta lactamase inhibitors. The
avibactam antibiotics do not have a beta lactam ring in their structure and thus are protected
from the adverse action of the beta-lactamase and carbapenemase enzymes[1].
The beta-lactamase enzymes and the carbapenemase enzymes are the target of this
particular drug. The target population for this drug involves a wide range of gram positive
and gram negative bacteria[2]. The drug binds reversibly with the serine beta-lactamase
enzymes by covalent bonding and inhibits them, so the beta-lactam drugs like penicillin and
cephalosporin groups of antibiotics can work properly against the bacteria[1].
Mechanism of Action:
Normally the avibactam drugs do not have any adverse effect on the bacteria.
However, this drug is effective against the bacteria, who have developed resistance against
the beta-lactam drugs. The beta lactam drugs like penicillin, cephalosporin and carbapenemes
prevent bacterial cell wall synthesis and eventually kill the bacteria. The beta-lactamase
enzymes and the carbapenemase enzymes help in the development of resistance against those
beta-lactam antibiotics by hydrolysing the beta-lactam rings[3].
When avibactam is used with the beta-lactam drugs, it binds covalently with the
serine beta-lactamases and prevents them from destroying the beta-lactam rings in the beta-
lactam drugs. As a result, the beta-lactam antibiotics are able to act effectively against the cell
wall of the bacteria and thus those drugs are able to impart a proper cidal effect on their target
bacterial population by preventing their growth[4].

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Figure: Mechanism of Action of Avibactam
Source: (Qin, Panunzio and Biondi, 2014)[5]
Adverse Effects of the Drug:
The avibactam drugs are mainly used with the ceftazidime antibiotic. The two drugs
are called Avycaz together. Hence there cannot be any individual side effect detected for this
particular drug. However, the overall side effects include the headache, nausea, diarrhoea,
anxiety, constipation and various others. The side effects might result from the allergic
condition in the patients against the beta-lactam drugs that are used with the avibactam
drug[6]. Another possible instance of the display of the adverse effects can be that the drugs
accidentally kills various good bacteria that are present in the stomach. Those bacteria are
involved in various beneficiary functions that are carried out in the body like vitamin
production, mucus production and protection of the body against the other harmful
microorganisms. Upon their destruction, there is a risk of further infections by other
microorganisms like fungus and viruses. Diarrhoea and stomach pain are often a resulting
event from that[7].
Specificity for Target Organism:
Avibactam works against a wide range of bacteria, including both the gram-positive
and the gram-negative bacteria. However, the principal target for this drug is the bacteria
which have developed multi-drug resistance against the beta-lactam drugs. The examples
include the multi-drug resistant Enterobacteriaceae family and Pseudomonas sp.[8]

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References:
1. Nichols WW, Newell P, Critchley IA, Riccobene T, Das S. Avibactam
pharmacokinetic/pharmacodynamic targets. Antimicrobial agents and chemotherapy.
2018 Jun 1;62(6):e02446-17.
2. Santevecchi BA, Smith TT, MacVane SH. Clinical experience with
ceftazidime/avibactam for treatment of antibiotic-resistant organisms other than
Klebsiella pneumoniae. International journal of antimicrobial agents. 2018 Apr
1;51(4):629-35.
3. Tuon FF, Rocha JL, Formigoni-Pinto MR. Pharmacological aspects and spectrum of
action of ceftazidime–avibactam: a systematic review. Infection. 2018 Apr
1;46(2):165-81.
4. Kapoor G, Saigal S, Elongavan A. Action and resistance mechanisms of antibiotics: A
guide for clinicians. Journal of anaesthesiology, clinical pharmacology. 2017
Jul;33(3):300.
5. Qin, W., Panunzio, M. and Biondi, S. (2014). β-Lactam Antibiotics
Renaissance. Antibiotics, 3(2), pp.193-215.
6. Rashid MU, Rosenborg S, Panagiotidis G, Löfdal KS, Weintraub A, Nord CE.
Ecological effect of ceftazidime/avibactam on the normal human intestinal
microbiota. International journal of antimicrobial agents. 2015 Jul 1;46(1):60-5.
7. Santevecchi BA, Smith TT, MacVane SH. Clinical experience with
ceftazidime/avibactam for treatment of antibiotic-resistant organisms other than
Klebsiella pneumoniae. International journal of antimicrobial agents. 2018 Apr
1;51(4):629-35.
8. Sy SK, Zhuang L, Xia H, Beaudoin ME, Schuck VJ, Derendorf H. Prediction of in
vivo and in vitro infection model results using a semimechanistic model of avibactam

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and aztreonam combination against multidrug resistant organisms. CPT:
pharmacometrics & systems pharmacology. 2017 Mar 1;6(3):197-207.