nutheme

What is Cefpodoxime ??

• An extended spectrum, third generation cephalosporin antibiotic.
• Bacetrial – Arrests the cell wall assembly leading to bacterial cell death.
• Active against most Gram +ve & -ve bacteria and stable in presence of β-lactamases.
• Excellent eradication potency against Typhoid and Respiratory tract infections
• Usual dosing in RTI – 200mg BD for 5-7 days.

What is Ofloxacin ??

• A chemotherapeutic antibiotic of fluoroquinolone class.
• Bacetrial – Inhibits the super coiling activity of bacterial DNA gyrase, halting DNA replication.
• Broad antibacterial spectrum against aerobic Gram –ve & +ve bacteria.
• Highly efficient penetration into body tissues and fluids.
• Adverse effects during ofloxacin therapy are infrequent, usually mild to moderate in intensity.
• Usual dosage for ofloxacin is 200 to 400 mg orally every 12 hours for 7 to 14 days.

Rationale of Combination

It has been demonstrated by recent studies. Concomitant administration of Cefpodoxime and Ofloxacin shows better symptoms relief compared with the modest improvement of upper respiratory tract infections like Rhintis, Sinusitis, Pharyngitis and Lower respiratory tract infections and help to cure Pneumonia, Acute bronchitis, tuberculosis and Thyphoid.

Therapeutic Evidence Favouring this Medication Therapy

• Clinically improved immunological parameters.
• Wide range of bacterial infections covered due to wide antibacterial spectrum.
• Short course therapy with effective cure.
• Resistance patterns of respiratory pathogens favours this medication therapy.

USPs of the Combination of Cefpodoxime + Ofloxacin

• Wider spectrum of activity against RTI pathogens.
• Prevents attainment of antimi crobialresistance by eliminating montherapy .
• Faster cure
• Better success rate.
• Less chances of relapse.
• Double attack of organisms since the mode of action is different, hence assuring complete cure.
• Allows for Synergistic effect of the drugs.
• Better patient compliance – the patients has to take only one tablets as against 2 separately.

Clinically Improved Immunological Parameters

• Improved cough with reduced mucus or sputum.
• Chest pain or tightness cured to an effective level.
• Improvement of leukocytosis and arterial oxygen tension.
• Peripheral blood cell analysis showed a decrease in natural killer cell counts and in helper/suppressor T cell ratio.
• Superoxide production by peripheral blood white cells decreases after treatment.
• Tonsilitis symptoms like Sore throat, pain upon swallowing diminishes.
• Reduced nasal discharges or congestion.
• Recovered physical health with no fever or weakness.

Wide Range of Bacterial Infections Covered Due to Wide Antibacterial Spectrum

• Lower respiratory infections –
  Pneumonia- Inflammatory condition of lungs.
  Acute bronchitis– Inflammatory of large bronchi in lungs.
  Tuberculosis– Persistant bacterial infection of lungs.
• Upper respiratory tract infections –
  Rhinitis – Irritation and inflammation of nose.
  Sinusitis – Inflammatory of sinuses
  Pharyngitis– Inflammatory of the throat.
• Typhoid Fever is a common worldwide illness, transmitted by the ingestion of food or water contaminated with the feces of an infected person, which contain the bacterium Salmonella enteric a serovar Typhi. Charactrized by slowly progressive fever, profuse sweating and gastroenteritis.

Pathogens Responsible For RTI

PATHOGEN	AQM (%)	ABRS (%)	AECBs (%)	CAP (%)
Streptococcus Pneumoniae	29	36	15-30	20-60
Haemophillus Influenzae	26	26	40-60	3-10
Moraxella Catarrhalis	12	2	15-30	1-2

Most Common Bacterial Pathogens in AOM, ABRS, AECBs, and CAP.

Typhoid fever bacterial (Salmonella Typhi) is the organism responsible for typhoid fever.

Recommended Medications with Their Limitations

• Improved cough with reduced mucus or sputum.
• Macrolides: – Azithromycin, Erythromycin and Clarithromycin.
• Coverage: – Betahemolytic Streptococci, pneumococci, staphylococci And enterococci including mycoplasma, rickettsia and Chlamydia.
• Dosage: – Azithromycin 250 mg/day. Single 2g dose for gonorrhea.
• Limitations: Less active against Gram positives. Gastric irritation.

---

• Penicillins- like amoxicillin and ampicillin are often employed for Symptomatioc relief from RTI infections.
• They have a good coverage against Gram positive organisms and anaerobes, less Gram negative coverage.
• Dosage: – Amoxicillin 250mg – 500mg for 5-7 days.
• Limitations:
  • Inactive against β lactamase producing bacterial strains and atypical.
  • Risk of allergic reactions in hypersensitive cases.

---

• Cephalosporins – are well accepted in the treatment of RTI, UTI infections and Typhoid.
• Have a wide antibacterial spectrum against Gram +ve and – ve organism.
• Cefpodoxime- is about 86% effcacous in treatment of typhoid fever because of favourable pharmacokinetic profile.
• Cefpodoxime and Cefixime is used in a dose of 200 mg BD for 5-7 days .
• Limitations:
  In active against atypical organism which form a major part of RTI.

Bacterial Resistance – A Menace

• Increased bacterial resistance to current antibiotics is a growing public health concern.
• The widespread use of antibiotics both inside and outside of medicine is playing a significant role in the emergence of resistant bacteria.
• Antibiotic resistance can be a result of horizontal gene transfer and also of unlinked point mutations in the pathogen genome at a rate of about 1in 108 per chromosomal replication.

Measure to Tackle the Menace of Bacterial Resistance

• Finding new drug with focused antibacterial spectrum.
• Opting for combination of drugs that aid in eradication of bacteria with dual attack mechanisms.
• Antibiotic resistance can be a result of horizontal gene transfer and also of unlinked point mutations in the pathogen genome at a rate of about 1in 108 per chromosomal replication.

Resistance Patterns of Respiratory Pathogens Favors this Medication Therapy

	Country	Intermediate Penicillin Resistance	High–level Penicillin Resistance	Macrolide Resistance
	USA (five centres)	13-17	11-37	2-21
	France	20	29	46
	Germany	15	0	6
	South Africa	26	5	8

a Penicillin resistance was defined as: intermediate (MIC 0. 12-1.0mg/L) and high–level (MIC > 1.0mg/L). Macrolide resistance was defined as erythromycin MIC ≥ mg/

Resistance Patterns of Respiratory Pathogens Favors This Medication Therapy

Resistance in H.influenzae
Alexander Project data from 1992 – 1997 indicate that the prevalence of β - lactamase production appears to have reached a steady state in some countries, such as France and the USA, but may be as high as 35% in some areas. Although use of a vaccine against H. Influenzae serotype b (the most virulent serotype) may decrease the importance of this strain, resistant, non – type able strains remain clinically significant community – acquired respiratory tract pathogens.
Resistance in M.catarrhalis
Most (50-80%) isolates of M.catarrhalis isolated during the Alexander Project in 1992 produced β - lactamase. However, this had increased further, to 90-100%, in the participating centres by 1997. Resistance to other (non β-lactam) antibiotic classes was stable in M. catarrhalis (as it was in H. Influenzae).

Cefpodoxime Ofloxacin- A better comparator to other commonly used medicines

	Amoxicillin	Cefixime	Cefpodoxime + Ofloxacin
Gram +ve Organisms	✔	✔	✔
Gram -ve Organisms	✔	✔	✔
A Typical Organisms	✘	✘	✔

Efficient Cure of Typhoid Fever

• High biliary concentration of this combination antibiotic enhance the killing of organisms persisting in biliary passage and thus reduce the rates of relapse and chronic carriage of typhoid pathogen.
• Overall cure rate with this therapy is over 90%.
• Moreover, this combination therapy has emerged as promising therapy for the treatment of enteric fever. Also, this therapy has a favorable pharmacokinetic profile, which allows twice – daily administration.