Principles of Antimicrobial Therapy

The choice of the antimicrobial used for the treatment of an infection is influenced by several factor: the age of the patient, the site of infection, immune status of the patient, efficacy of the drug, the profile of adverse effects, the prevalence of anti-microbial resistance and the concomitant presence of other systemic diseases or organ dysfunction.
The cephalosporins include three generations of agents. The second generation extends the antimicrobial spectrum of the first generation to include wide range of gram negative rods and Pseudomonas.
The -lactams act by inhibiting the incorporation of peptidoglycon into the bacterial cell wall. Penicilin G still remains the drug of choice for syphilis, meningococci, clostridia and pneumococcous. Ampicillin has an extended spectrum of activity aganst gram negative rods(Salmonella, Hemophilus influenzae). Penicillinase-resistant penicilins are the drugs of choice for infections due to -lactamase producing staphylococci. Piperacillin and ticarcillin are antipseudomonal penicillins.

Diagnostic methods in infectious diseases

Microbiologic confirmation of an infectious diseses may be obtained by direct demonstration of the organism, by growing the organism in culture or by serologic method.
Direct demonstration of an infective agent may be:
 By direct microscopy: India ink preparation(cryptococi), dark ground illumination(vibrio spirochestes), KOH preparation(dermatophytes) and wet wount(stool parasites).
 By staining:Gram stain(malaria),Giemsa stain(chlamydia), Ziehl-Nielsen stain(acid-fast bacilli), silver stains(pneumocystis).
 By antigen detection using latex agglutination teste. (meningococcus, pneumcococcus) and enzyme immunoassay.
 Culture method: Proper collection technique(for clinical specimen), suitable transport and culture media and optimal growth conditions may be requuired for fastidious organisms(such as anaerobes), phenotyphic characterization may be done and antibiotic sensitivity determined after culture of the organism.
 Serologic method: This method may be the only method for diagnosing viral, rickettisal, chalamydial and mycoplasma infections. Serology also provides supportive evidnce for certain bacterial infections( also for streptococci, widal for typhoid).

Fever

Fever of more than three weeks duration remaining undiagnosed after a week of hospitalization is defined as pyrexia of unknown origin (PUO).
PUO may be due to the infections, malignancy, inflammatory diseases, drugs or factitious. Infections are the leading causes of PUO tuberculosis often extrapulmonary, HIV infection, infective endocarditis, prolonged mononucleosis, intraabdominal abscess and fungal infections.
Malignancies associated with PUO are lymphomas, leukemia, renal cell carcinoma and hepatoma. Immunoinflammatory causes of PUO include SLE and adult Still’s diseases.
A proper detailed history and physical examination is critical in estabilishing a dignosis and for planing investigations. The pattern of fever is seldom diagnostic by itself. Drug history, occupational hisory and sexual practices are important areas that need to be investigated.
Routine haematologic and urinary investigations, serum chemistry and chest X-ray are important investigations in all patients. A markedly elevated ESR may indicate an infection or immunoinflammatory diseases, temporal athritis, Still’s diseases. US/CT may be obtained for evaluating hepatobiliary, renal, retroperitoneal and pelvic sources of PUO and for screening for occult primaries. An echocardiogram may be ordered if endocarditis is suspected. Biopsy of the bone marrow or liver may be useful if the non-invasive investigations do not yield a definitive diagnosis.
In the absence of a definite diagnosis, a therapeutic trial of antitubercular therapy may be instituted for six weeks.
Causes of prolonged fever
• Infections
o Polygenic infection: pyogenic abscess, cholangitis, pelvic abscess, diverticular abscess, thermbophlebitis.
o Vascular infection: Infective endocartitis, infected vascular access devices.
o Chronic granulomatious infection: Tuberculosis, atypical mycobacterial infections, fungal infection.
o Other prolonged bacterial and rickettisial illnesses: Brucellosis, chronic meningococcemia.
• Immunoinflammatory diseases: Systemic lumps erythematosus, juvenile rheumatoid arthritis(stills diseases), vasculitis including giant cell arthritis.
• Neoplasms: Primary (renal, pancreas, hepatic, lung, colon), secondary(hepatic secondaries), lymphoid neoplasms(lymphomas).
• Granulomatous conditions: Sarcoidosis.
• Metabolic and familial conditions: Familial Mediterranean fever, Fabry’s diseases.
• Drug induced fever
• Factitious fever
• Undiagnosed fever.