A child was admitted to the hospital with H. influenza meningitis. Cefotaxime is preferred over ampicillin because:
Ans. d. Cefotaxime is more active against beta-lactamase (Ref: Ananthanarayan 9/e p327, 8/e p331; Harrison 19/e p1011, 18/e p1228; Nelson 19/e p941,942)"Cefotaxime or ceftazidime is the drug of choice for the treatment of Hemophilus meningitis. Ampicillin and cotrimoxazole were popular for respiratory infections, but as plasmid-borne resistance to these drugs is now common, thus amoxicillin-clavulanate or clarithromycin is more effective. Plasmid for beta lactamase production makes them resistant. "--Ananthanarayan 9/e p327"Antibiotic Resistance: Most H, influenzae isolates are susceptible to ampicillin amoxicillin, but about a third produce a beta-lactamase and are therefore resistant beta-Lactamase-negative ampicillin-resistant (BLNAR) isolates have been identified that manifest resistance by production of a beta-lactam-insensitive cell wall synthesis enzyme called PBP3. Amoxicillin-clavulanate is uniformly active against H. influenzae clinical isolates except for the rare BLNAR isolates. Among macrolides azithromycin is active against about 99% of H. influenza isolates; in contrast, the activity of erythromycin and clarithromycin against H. influenzae clinical isolates is poor. H. influenzae resistance to 3rd- generation cephalosporins has not been documented. Resistance to trimethoprim-sulfamethoxazole is infrequent ([?]10%) and resistance to quinolones is believed to be rare. ""Initial therapy for meningitis due to Hib should consist of a cephalosporin such as ceftriaxone or cefotaxime. Administration of glucocorticoids to patients with Hib meningitis reduces the incidence of neurologic sequelae. Many infections caused by non-typable strains of H. influenzae, such as otitis media, sinusitis, and exacerbations of CO PD, can be treated with oral antimicrobial agents. Approximately 20-35% of non-typable strains produce B-lactamase (with the exact proportion depending on geographic location), and these strains are resistant to ampicillin. Several agents have excellent activity against non-typable H. influenzae, including amoxiciltin/clavulanic acid, various extended-spectrum cephalosporins, and the macrolides, azithromycin and clarithromycin. In addition to B-lactamase production, alteration of penicillin- binding proteins--a second mechanism of ampicillin resistance--has been detected in isolates of H. influenzae. "--Harrison 19/e p 1011"Clinically; meningitis caused by H. influenzae type b cannot be differentiated from meningitis caused by Neisseria meningitidis or Streptococcus pneumoniae. Antimicrobial therapy should be administered intravenously for 7-14 days for uncomplicated cases. Cefotaxime, ceftriaxone, and ampicillin cross the blood-brain barrier during acute inflammation in concentrations adequate to treat H. influenzae meningitis. Intramuscular therapy with ceftriaxone is an alternative in patients with normal organ perfusion. "--Nelson 19/e p941Hemophilus influenzae (Pfeiffer's bacillus)Morphology:Non-motile, non-sporing, oxidase positive, gram negative bacilliQCapsulated coccobacilli shows pleomorphismQStained by Loeffler's methylene blueQ or Dilute carbol fuschinQDivided into 8 biotypes on the basis of indole production, urease and ornithine decarboxyalse activityQCulture:Fildes agar is the best for primary isolationQOn Levinthal's mediumQ, capsulated strains show distinctive iridesecenceRequires both X factor (heat stable hemin) and V factor (heat labile coenzyme present in RBC), so heated or boiled blood agar is superior to plain agarQShows "Satellitisre"' (dependence on V factor) when S. aureus is streaked across the blood agarAntigenic properties:Hemophilus influenzae is the first free living organism whose complete genome is sequencedQThere are three major surface antigen- the capsular polysaccharide, the outer membrane protein, and Iipo-oligosaccharideQMajor antigenic determinant is capsular polysaccharideQ based on which, it is typed into six capsular typesMost isolates from acute invasive infections belong to type bQType b capsule has unique structure containing pentose sugar (ribose and ribitol) in the form of polyribosyl ribitol phosphate (PRP) Q instead of hexose and hexosaminesTypes of Hemophilus influenzaeInvasiveNon-invasive* Bacillus acts as a primary pathogen, causing acute invasive infectionsQ.* Bacilli spread through blood, being protected from phagocytes by their capsuleQ.* Meningitis is the most important infection in this group.* Others: Laryngoepiglottits, conjunctivitis, bacteremia, pneumonia, arthritis, endocarditis and pericarditis.* Usually seen in children* Caused by the capsulated strains, type b accounting for most cases.* Bacillus spreads by local invasion along mucosal surfacesQ* Causes secondary or superadded infections, usually of the respiratory tractQ.* These include otitis media, sinusitis and exacerbations of chronic bronchitis and bronchiectasisQ.* Usually seen in adultsQ* Caused by non-capsulated strainsQClinical Features:Meningitis & respiratory tract infection are the most common presentationQ.MeningitisMost frequently caused by biotype-1QOccur in childrenQ due to absence of PRP antibodiesSubdural effusionQ is the MC complicationDOC is ceftriaxone or cefotaximeQHemophilus influenzae is called Pfeiffer's bacillus but Pfleffer's phenomenon (bacteriolysis in vivo) is associated with V. choleraQ (cholera vibrios were lysed when injected intraperitoneally into specifically immunized guinea pigs)OrganismDrug of Choice* Streptococcus pneumoniae. S. viridans. Hemolytic streptococci group A, B, C, G* Staphylococcus (non-penicillinase producing)* Actinomyces, Bacillus cereus, Clostridium* Neisseria meningitidis* Treponema pallidum, T. pertenuePenicillin GQ* MRSA, Coagulase negative Staphylococcus* Enterococcus faeciumVancomycinQ* Enterococcus faecalis. ListeriaAmpicillinQ* Bacillus anthracis* Borrelia burgdorferi, B. recurrentis* Chlamydia & RickettsiaeDoxycyclineQ* CorynebacteriumErythromycinQ* Hemophilus ducreyi & MycoplasmaAzithromycinQ* NocardiaCotrimoxazoleQ* E. coli, Klebsiella, Proteus* SalmonellaCeftriaxoneQ* Serratia, Enterobacter, AcinetobacterCarbapenemsQ (SEA)* BacteroidesMetronidazoleQ
Cefotaxime is more bioavailable
Cefotaxime is more active against altered penicillin binding protein
Drug of choice is trimethoprim sulfamethoxazole but cannot be given
Cefotaxime is more active against beta-lactamase
Bacteria