The aim of the paper: The identification of the importance of bacterial resistance and the need for cost-effective antibiotics.
Materials and methods: To perform this study have been considered 444 patients under treatment with antibiotics, who have used 621 antibiotics (about 1.4 antibiotics per patient) in the Mother Theresa University Hospital Centre.
Results: The minimum inhibitory concentration (MIC) of doripenem against microorganisms like S.aureus, P.aeruginosa, E.coli, Enterobacter, P.mirabilis is lower than other carbapenems. Comparative studies with Imipenem and Tazocine resulted that Doripenem costs less and the hospitalization days are shorter.
Key words: bacterial resistance, doripenem, cost-efficacy
Introduction
In the past years, antibiotics have been critical in the fight against infectious disease caused by bacteria and other microbes. Antimicrobial chemotherapy has been a leading cause for the dramatic rise of average life expectancy in the Twentieth Century. However, disease-causing microbes that have become resistant to antibiotic drug therapy are an increasing public health problem. Wound infections, gonorrhea, tuberculosis, pneumonia, septicemia and childhood ear infections are just a few of the diseases that have become hard to treat with antibiotics.
Nowadays, about 70 percent of the bacteria that cause infections in hospitals are resistant to at least one of the drugs most commonly used for treatment. To prevent and to treat infections is very important to know which is the best antibiotic to use, but the increasing use and the misuse of antibiotics are the most common ways that led to bacterial resistance. When the microorganism is capable to survive the antibiotic this is due to genetic mutation, as the major cause. Bacterial resistance could be a result of gene horizontal transfer (conjugation, transduction, transformation).
The main mechanisms of bacterial resistance are: the drug inactivation or modification through bacterial enzymes like β-lactamase, the alteration of the target (PBP changes to MRSA in penicillin), the alteration of metabolic pathways (the sulfonamide resistant microorganisms do not seek for PABA-which is the precursor of the synthesis of folic acid and nucleic bacterial acid), a decrease in drugs accumulation.
The increase of the microbial development of resistance against antibiotics, resulting in the increase of the treatment costs, is the main reason why we undertook this study in order to decrease the treatment costs of the infectious diseases.
Materials and methods
To perform this study have been considered 444 patients under treatment with antibiotics, who have used 621 antibiotics (about 1.4 antibiotics per patient). The patients in the study were treated in the infectious diseases service, the pediatric infectious diseases service and the urology service in the Mother Theresa University Hospital Centre.
The study is conducted in these services because of the specifics of the pathologies, remembering that the intervenes in the urology service by nature are intervenes in not sterile fields, while in infectious services (like infectious diseases service and the pediatric service) very often is hard to select the right one antibiotic.
Results
From this study is obvious the increased bacterial resistance of microorganisms like E.coli, P.aeruginosa, P.mirabilis, E.faecalis. In the table below is noticed that ampicillin is not the first choice because the resistance against it is very high, but even cefuroxime and ciprofloxacin should not be considered as the best choices.
Table No. 1
Percentage of bacterial resistance in the Mother Theresa University Hospital Centre (%)
Antibiotics
| Antibiotics | E.coli | P.mirabilis | P.aeruginosa | E.faecalis |
| Amicacin | 29 | | 56 | |
| Amoxicillin | 50 | | 100 | |
| Ampicillin | 100 | 100 | 100 | |
| Cefepim | 50 | | 11 | |
| Cefotaxim | 57 | | 100 | |
| Ceftazidim | 57 | | 11 | |
| Cefuroxim | 57 | | 100 | |
Table No. 2
Percentage of bacterial resistance in the Mother Theresa University Hospital Centre (%)
| Antibiotics | E.coli | P.mirabilis | P.aeruginosa | E.faecalis |
| Ciprofloxacin | 50 | | 89 | 83 |
| Gentamicin | 57 | | 89 | 100 |
| Meropenem | | | 11 | |
| Tazocin | 14 | | 11 | |
| Sulf/Trimethoprim | 64 | 100 | 100 | 100 |
| Levofloxacin | | | | 57 |
| Moxifloxacin | | | | 25 |
| Cefaclor | 86 | | 100 | |
Doripenem has three approved indications:
-Nosocomial pneumonia (NP), including ventilator-associated pneumonia (VAP)
-Complicated intra-abdominal infections (cIAI)
-Complicated urinary tract infections (CUTI).
Table No. 3
In vitro activity for different carbapenems
Doripenem displays low in vitro MICs (mcg/ml) for gram positive pathogens.
| | Doripenem | Meropenem | Imipenem |
| S.aureus | 0.06-32 | 0.12-32 | 0.5-32 |
| E.faecalis | 8 | 16 | 4 |
| S.pneumonie | 0.008-1 | 0.008-1 | 0.5-1 |
| S,viridans | 0.5 | 0.5 | 0.5 |
| S.betahemolitic | 0.03 | 0.06 | 0.5 |
| E.faecium | >16 | >16 | >8 |
Table No. 4
Doripenem displays low in vitro MICs (mcg/ml) for gram negative pathogens.
| | Doripenem | Meropenem | Imipenem |
| E.coli | 0.03-0.06 | 0.03-0.06 | <0.05 |
| Klebsiella | 0.06-0.12 | 0.12 | <0.05 |
| Enterobacter spp Ceftazidim resistant | 0.12-0.25 | 0.25 | 1 |
| Citrobacter spp Ceftazidim resistant | 0.06-0.12 | 0.06-0.12 | 1 |
| P.mirabilis | 0.25 | 0.12 | 2 |
| Serratia spp Ceftazidim resistant | 0.25-0.5 | 0.12-0.5 | 1-2 |
| Salmonella spp | 0.06 | 0.03 | <0.05 |
| Shigella spp | 0.06 | 0.03 | <0.05 |
| P.aeruginosa | 8 | 16 | >8 |
| Acinetobacter | 4 | 8 | 2 |
Doripenem dosing regimen is: 500 mg (100 ml/1 hour), 250 mg (50 ml/1 hour). Recommended: 500 mg every 8 hours venous infusion lasting 1 hour, over 18 years old.
Discussion
Microbial development of resistance, as well as economic incentives, has resulted in research and development in the search for new antibiotics in order to maintain a pool of effective drugs at all times. Disease-causing microbes that have become resistant to antibiotic drug therapy are an increasing public health problem. One part of the problem is that bacteria and other microbes that cause infections are remarkably resilient and have developed several ways to resist antibiotics and other antimicrobial drugs. Another part of the problem is due to increasing use, and misuse, of existing antibiotics in human medicine, also the poor sanitary conditions in our hospitals.
The minimum inhibitory concentration of doripenem for bacteria like S.aureus, P.aeruginosa, E.coli, Enterobacter spp, P.mirabilis is lower than other carbapenems. Doripenem is the best combination of the intrinsic activity of meropenem against gram negative bacteria and the intrinsic activity of imipenem against gram positive bacteria. From the comparative studies with tazocin and imipenem resulted that doripenem costs less and lowers the hospitalization at least 15 %.
Knowing the efficacy of this antibiotic against resistant microorganisms, the good safety profile and the low cost of treatment, we recommend the hospital use of this antibiotic in the infectious diseases service.
References
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