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40 Cards in this Set

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H. influenzae is on of the classic _______ ________ bacteria.

encapsulated pyogenic

H influenzae causes which diseases?

Sinusitis, otitis media, and pneumonia are common. Epiglotittis is uncommon but H influenzae is the most important cause. H. influenzae used to be the leading cause of meningitis but the vaccine has greatly reduced the number of cases.

Characteristics of H. influenzae?

Small, gram negative coccobacillary rods. Requires factors X (hematin) and V (NAD) for growth. Of the 6 polysaccharide types, type b causes 95% of invasive disease. Type b capsule is polyribitol phosphate.

Where is H influenzae found? What is the transmission?

Upper respiratory tract. Respiratory droplets.

Pathogenesis of H influenzae?

Polysaccharide capsule is the most important virulence factor. Unencapsulated ("untypable") strains cause mucosal infections but NOT invasive infections. IgA protease is produced.



Most causes of meningitis occur in kids younger than 2 years of age, because maternal Abs has waned and the immune response of the child to capsular polysaccharides can be inadequate.



No exotoxins identified.

How do you diagnose an infection with H. influenzae?

Gram-stained smear with culture on chocolate agar. Growth requires factor X and V.



Determine serotype by using antiserum in various tests (e.g. latex agglutination). Capsular antigen can be detected in serum or CSF. Cannot use serum to detect antibodies

Treatment of infection with H. influenzae?

Ceftriaxone for meningitis. About 25f% of strains produce beta-lactamase.

How do you prevent infection with H. influenzae?

Vaccine containing the type b capsular polysaccharide conjugated to diptheria toxoid or other protein is given between 2 and 18 months of age.



Rifampin can prevent meningitis in close contacts.

Into which class do cephalosporins fall?

beta-lactam antibiotics.

How do cephalosporins work?

inhibit bacterial cell wall synthesis

What is different about cephalosporins compared to penicillins?

Cephalosporins arent as susceptible to penicillinases and beta-lactamases and therefore have a broader spectrum of activity.

Which bacteria express extended-spectrum beta-lactamases that can hydrolyze most cephalosporins?

E coli and Klebsiella species.

Which are the 1st generation cephalosporins?

cefazolin, cefadroxil, cephalexin, etc.

Against which types of bacteria are 1st gen cephalosporins effective?

Gram-positive cocci (pneumococci, streptococci, and staphylococci).



Other examples: E coli, K pneumoniae, and proteus mirabilis are often sensitive. Anaerobic cocci (eg peptococci, peptostreptococci) are usually sensitive



NOT sensitive bacteria: P aeruginosa, indole-positive proteus species, Enterobacter sp, S marcescens, Citrobacter sp, and Acinetobacter sp.



Traditionally not active against methicillin resistant strains of staphylococci.

What is the pharmacokinetics of oral 1st gen cephalosporins?

absorbed from the gut, urine concentrations are usually high. Tissue levels are usually lower than serum levels.



Excretion is mainly by glomerular filtration and tubular secretion into the urine. Drugs that block tubular secretion (Probenecid) may increase serum levels substantially. In patients with impaired renal function, dosage must be reduced.

Which 1st gen cephalosporin is parenteral?

cefazolin.

Which circumstances do you use 1st gen cephalosporins?

Oral: UTIs and staphylococcal or streptococcal infections, including cellulitis, or soft tissue abscess. Do not rely on them for serious systemic infections.



Parenteral: Cefazolin penetrates well into most tissues. it is the drug of choice for surgical prophylaxis. It may also be used as the least toxic drug (eg penicillinase-producing e coli or k pneumoniae) and in individuals with staphylococcal or streptococcal infections who have a history of penicillin allergy other than immediate hypersensitivity.



Cefazolin does not penetrate the CNS

Which drugs are 2nd gen cephalosporins?

Cefaclor, cefamandole, cefonicid, cefuroxime, cefprozil, etc. Cephamycins (cefoxitin, cefmetazole, and cefotetan) are structurally related and in this category as well (have activity against anaerobes).

In general, 2nd gen cephalosporins are active against organisms inhibited by first-generation drugs but also have extended _______ __________ coverage.

Gram negative

Which organisms are sensitive to 2nd gen cephalosporins but not 1st gen?

Klebsiella sp and H influenzae (to some drugs)

As with 1st gen cephalosporins, no 2nd gen are active against ________ or __ ________.

enterococci; P aeruginosa

Even though 2nd gen cephalosporins may exibit activity against ________ sp, they should not be used because of resistant mutants that constitutively express a chromosomal beta lactamase that hydrolyzes these drugs.

Enterobacter sp.

Clinical uses of 2nd gen cephalosporins?

Oral: active against beta-lactamase- producing H influenzae or moraxella catarrhalis and have been primarily used to treat sinusitis, otitis and lower respiratory tract infections, in which these organisms have an important role.



Because of their mixed activity against anaerobes (including many B fragilis (cause of colitis) strains), cefoxitin, cefotetan or cefmetazole can be used to treat mixed anaerobic infections such as peritonitis, diverticulitis, and PID.



Cefuroxime is used to treat community acquired pneumonia because it is active against beta-lactamase-producing H influenzae or K pneumoniae and some penicillin-non-susceptible pneumococci.



Cefuroxime crosses BBB but less effective in tx of meningitis than ceftriaxone or cefotaxame and should not be used.

Which drugs are 3rd gen cephalosporins?

Cefoperazone, cefotaxime, ceftazidime, ceftizoxime, ceftriaxone, cefixime, cefpodoxime proxetil, cefdinir, cefditoren pivoxil, ceftibuten and moxalactam.

What is different about 3rd gen cephalosporins compared to other generations?

Expanded gram-neg coverage and some are able to cross the BBB.



Active against Citrobacter, S marcescens, and Providencia (although resistance can emerge during tx of infections caused by these species due to production of cephalosporinases). also effective against beta-lactamase-producing strains of haemophilus and neisseria.

Which 2 drugs are the only ones with useful activity against P aeruginosa?

Ceftazidime and cefoperazone

Are 3rd gen cephalosporins reliably effective against enterobacter species?

No

Which bacteria produce cephalosporinases that, when constitutively expressed, can confer resistance to 3rd gen cephalosporins?

Serratia, Providencia, and Citrobacter.

Which two 3rd gen cephalosporins are active against B fragilis?

Cefizoxime and moxalactam.

Are all 3rd generation cephalosporins basically the same?

No! it is a very heterogeneous group... different pharmacokinetics, toxicity, action.

Can you use all 3rd gen cephalosporins against S aureus?

No... Cefixime, cefdinir, ceftibuten, and cefpodoxime proxetil are good for s aureus but Ceftibuten and cefixime have poor activity against it.

Which generation cephalosporin should I use if the bacteria strain is resistant to most other drugs?

3rd generation! (although if it expresses extended-spectrum beta-lactamases, it won't be susceptible).

Again, treatment with 3rd gen cephalosporins should be avoided in treatment of which infection?

enterobacter! Resistance could emerge

Which 3rd gen cephalosporins are approved for tx of meningitis caused by pneumococci, meningococci, H influenzae, and susceptible enteric gram-negative rods (but not monocytogenes)?

Ceftriaxone and cefotaxime



(chef with 3 axes and chef with tax form)

What does MIC stand for? Significance?

Minimum inhibitory concentration. The MIC of an antimicrobial that will inhibit pneumococcal growth identifies antimicrobial resistance. Meningitis caused by strains of pneumococci with penicillin MICs > 1mcg/mL may not respond even to these agents, and addition of vancomycin is recommended.



Which class is vanco in?

Inhibits cell wall synthesis by firmly adding to the D-ala-D-ala terminus of nascent peptidoglycan pentapeptide. This inhibits transglycosylase, preventing further elongation of peptidoglycan and cross-linking.

Which generation is active against P aeruginosa, enterobacteriaceae, S aureus, and S pneumonia? Give an example.

4th gen cephalosporins. Ex: Cefepime. Useful in the tx of enterobacter infections

Cephalosporins are _________ and may elicit a variety of __________ rxns that are identical to those of penicillins, including anaphylaxis, fever, skin rashes, nephritis, granulocytopenia, and hemolytic anemia.

Sensitizing; hypersensitivity

Why don't people with penicillin allergies have an allergy to cephalosporins?

the chemical nucleus of cephalosporins is sufficiently different from that of penicillins so that some individuals with a history of penicillin allergy may tolerate cephalosporins. Cross allergenicity does occur but its only 5-10%... more common in early generation cephalosporins.

Toxicity of cephalosporins?

local irritation can produce pain after IM injection and thrombophlebitis after IV injection.



Renal toxicity including interstitial nephritis and tubular necrosis has been demonstrated with several cephalosporins.



some also have a methylthiotetrazole group which may cause hypoprothrombinemia and bleeding disorders. Oral administration of vitamin K1 can prevent this.