Dear Akinboni MICHEAL Oluwaseun,

There are two kinds (types) of antibacterial agent stability: (1) stability (resistance) from destruction by beta-lactamase produced by bacteria. Third generation antibiotics are more resistant to bacteria than first and second generation (this is a relatively short answer). The other type of stability which means degradation of the antibacterial agent upon standing in aqueous solution (this is relatively long answer since each antibacterial agent has different stability from the others). For this kind of stability, please see the following publications:

1-Can J Hosp Pharm. 2010 May-Jun; 63(3): 212–224.

PMCID: PMC2901781

Language: English | French

1-Stability of Commonly Used Antibiotic Solutions in an Elastomeric Infusion Device

Objective:

To evaluate the stability of 5 antibiotics (cefazolin, ceftazidime, ceftriaxone, clindamycin, and vancomycin) in either 5% dextrose in water (D5W) or 0.9% sodium chloride in water (NS) after storage in Accufuser disposable silicone balloon infusers.

Methods:

The study drugs were reconstituted, according to the manufacturers’ directions, in polyvinyl chloride minibags with either D5W or NS, at 2 different concentrations. The resulting solutions were transferred to disposable silicone balloon infusers for storage at 4°C or at room temperature (23°C). The concentration of each drug in each solution was determined by validated stability-indicating liquid chromatographic methods after storage for 14 to 31 days.

Results:

Solutions of ceftriaxone in either diluent retained more than 95.2% of the initial concentration for 2 days at room temperature and more than 91.6% of the initial concentration for 14 days at 4°C. Solutions of cefazolin in D5W or NS retained more than 90% of the initial concentration for at least 3 days at room temperature and for at least 26 days at 4°C. Solutions of ceftazidime in D5W or NS retained more than 90% of the initial concentration for only 1 day when stored at room temperature and for at least 4 days at 4°C. Solutions of clindamycin or vancomycin in D5W or NS retained 90% of the initial concentration for at least 7.5 days at room temperature and at least 90% of the initial concentration for at least 27.8 days at 4°C.

Conclusions:

Previously reported expiration dates for solutions stored in elastomeric infusion devices were not based on 95% confidence intervals and were often longer than expiration dates determined from the studies reported here, which are based on 95% confidence intervals. Comparison of the observed concentrations remaining between previously published studies and the studies reported here indicates that the Accufuser elastomeric infusion device did not adversely affect the stability of these drugs.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2901781/

2-Stability of reconstituted amoxicillin clavulanate

potassium under simulated in-home storage

conditions

Nwokoye Peace, Oyetunde Olubukola and Akinleye Moshood

ABSTRACT

Oral suspensions of antibiotics are mainly available as dry powders for reconstitution. Many reconstituted antibiotic suspension is to be kept refrigerated in order to get the optimal benefit from the drug. However, many patients do not keep to the specified storage conditions for different reasons like no refrigerator and irregular power supply that may result in various degrees of degradation of the product. Pharmacists are therefore challenged on how to counsel

patients when there is no refrigeration or erratic power supply for refrigeration. This study investigated stability of amoxicillin-clavulanate potassium suspension in simulated in-home conditions of erratic power supply and no refrigeration. Amoxicilin clavulanate suspensions were reconstituted and stored in three different in-home storage conditions with temperature ranging between 5-29oC over a period of 10 days. Samples from the suspension were assayed using a validated HPLC method. Percentage concentrations of amoxicillin-clavulanate potassium were over 90% up to fifth day, degradation was extensive by seventh day with

amoxicillin concentration falling below 80% in two conditions while clavulanate had values less than 70% in all the three conditions. Reconstituted amoxicillin clavunate potassium stored at room temperature (27-29oC) is stable for five days, use of reconstituted suspension that was not properly refrigerated after the fifth day should be discouraged.

http://www.japsonline.com/admin/php/uploads/336_pdf.pdf

3- https://staff.najah.edu/sites/default/files/Problems_Associated_with_Reconstitution_Administration_and_Storage_of_Antibiotic_Suspensions_for_Pediatrics_in_Nablus_City_Palestine_0.pdf

4- http://mysccg.com/generalDocuments/Stability%20of%20Refrigerated%20and%20Frozen%20Drugs.pdf

5- ttps://www.researchgate.net/publication/268807306_Stability_of_reconstituted_cefuroxime_axetil_at_different_temperature_storage_conditions

6- https://www.google.ps/search?q=antibiotic+stability+chart&biw=1366&bih=667&tbm=isch&imgil=wdJLnNCkxK6fRM%253A%253B9prWAUiIIARJFM%253Bhttp%25253A%25252F%25252Fwww.google.com%25252Fpatents%25252FEP2086543A2%25253Fcl%2525253Den&source=iu&pf=m&fir=wdJLnNCkxK6fRM%253A%252C9prWAUiIIARJFM%252C_&usg=__wf2EaiRfKXyZrtvtLGGhAZeT4mQ%3D&ved=0ahUKEwie1t7JzfXKAhUBwhoKHRwcDZMQyjcIKQ&ei=ppW_Vp7rDYGEa5y4tJgJ#imgrc=o51oKUo3MxKzkM%3A

See charts

7- http://aem.asm.org/content/20/3/447.full.pdf

Regarding antibiotics resistance:

What is antibiotic resistance?

Antibiotic resistance occurs when an antibiotic has lost its ability to effectively control or kill bacterial growth; in other words, the bacteria are "resistant" and continue to multiply in the presence of therapeutic levels of an antibiotic.

Why do bacteria become resistant to antibiotics?

Antibiotic resistance is a natural phenomenon. When an antibiotic is used, bacteria that can resist that antibiotic have a greater chance of survival than those that are "susceptible." Susceptible bacteria are killed or inhibited by an antibiotic, resulting in a selective pressure for the survival of resistant strains of bacteria.

Some resistance occurs without human action, as bacteria can produce and use antibiotics against other bacteria, leading to a low-level of natural selection for resistance to antibiotics. However, the current higher-levels of antibiotic-resistant bacteria are attributed to the overuse and abuse of antibiotics. In some countries and over the Internet, antibiotics can be purchased without a doctor's prescription. Patients sometimes take antibiotics unnecessarily, to treat viral illnesses like the common cold.

How do bacteria become resistant?

Some bacteria are naturally resistant to certain types of antibiotics. However, bacteria may also become resistant in two ways: 1) by a genetic mutation or 2) by acquiring resistance from another bacterium.

Mutations, rare spontaneous changes of the bacteria's genetic material, are thought to occur in about one in one million to one in ten million cells. Different genetic mutations yield different types of resistance. Some mutations enable the bacteria to produce potent chemicals (enzymes) that inactivate antibiotics, while other mutations eliminate the cell target that the antibiotic attacks. Still others close up the entry ports that allow antibiotics into the cell, and others manufacture pumping mechanisms that export the antibiotic back outside so it never reaches its target.

Bacteria can acquire antibiotic resistance genes from other bacteria in several ways. By undergoing a simple mating process called "conjugation," bacteria can transfer genetic material, including genes encoding resistance to antibiotics (found on plasmids and transposons) from one bacterium to another. Viruses are another mechanism for passing resistance traits between bacteria. The resistance traits from one bacterium are packaged into the head portion of the virus. The virus then injects the resistance traits into any new bacteria it attacks. Bacteria also have the ability to acquire naked, "free" DNA from their environment.

Any bacteria that acquire resistance genes, whether by spontaneous mutation or genetic exchange with other bacteria, have the ability to resist one or more antibiotics. Because bacteria can collect multiple resistance traits over time, they can become resistant to many different families of antibiotics.

How does antibiotic resistance spread?

Genetically, antibiotic resistance spreads through bacteria populations both "vertically," when new generations inherit antibiotic resistance genes, and "horizontally," when bacteria share or exchange sections of genetic material with other bacteria. Horizontal gene transfer can even occur between different bacterial species. Environmentally, antibiotic resistance spreads as bacteria themselves move from place to place; bacteria can travel via airplane, water and wind. People can pass the resistant bacteria to others; for example, by coughing or contact with unwashed hands.

Can bacteria lose their antibiotic resistance?

Yes, antibiotic resistance traits can be lost, but this reverse process occurs more slowly. If the selective pressure that is applied by the presence of an antibiotic is removed, the bacterial population can potentially revert to a population of bacteria that responds to antibiotics.

http://www.tufts.edu/med/apua/about_issue/about_antibioticres.shtml

Hoping this will be helpful,

Rafik

Article Stability of reconstituted cefuroxime axetil at different te...

Thank you very much Mr. Rafik Karaman it was very helpful. However, it would be more appreciated of i get hints or articles and journals talking about the resistance of Escherichia coli to third-generation cephalosporins. Thanks.