P-Lactamase producers

Organism P-Lactamase producers, % Chromosomal Enzyme origin % Plasmid Richmond-Sykes classification... 

Low and high refer to the number of colony forming units (CPU) used to inoculate the media. Comparing MICs at low (10 ) and high (10 ) CPU, a large increase in MIC at the high inoculum level vs a P-lactamase producer is an indicator of instability via enzymatic hydrolysis. 

Complicated exacerbation FEV, less than 50% predicted Comorbid cardiac disease Greater than or equal to 3 exacerbations per year Antibiotic therapy in the previous 3 months Above organisms plus drug-resistant pneumococci, P-lactamase-producing H. influenzae and M. catarrhalis, Escherichia coli, Proteus spp., Enterobacter spp., Klebsiella pneumoniae Oral P-Lactam/P-Iactamase inhibitor (amoxicil 1 i n-clavulanate) Fluoroquinolone with enhanced pneumococcal activity (levofloxacin, gemifloxacin, moxifloxacin) Intravenous P-Iactam/P-Iactamase inhibitor (ampicillin-sulbactam) Second- or third-generation cephalosporin (cefuroxime, ceftriaxone) Fluoroquinolone with enhanced pneumococcal activity (levofloxacin, moxifloxacin)... 

Health care MRSA, extended-spectrum P-lactamase-producing K. pneumoniae, P. aeruginosa, Acinetobacter spp. 

Amoxicillin 1.5-4 g/day in 2-3 doses 90 mg/kg per day in 2 doses Lacks coverage against P-lactamase producers... 

Human Viridans streptococci, Staphylococcus aureus, Eikenella corrodens, Elemophilus influenzae, and P-lactamase-producing anaerobic bacteria. 

Resistant to p-lactamases produced by gram-negative rods. 

Kaniga K, Flamm R, Tong SY, Lee M, Friedland I, Redman R. (2010) Worldwide experience with the use of doripenem against extended-spectrum-P-lactamase-producing and ciprofloxacin-resistant enterobacteriaceae Analysis of sixphase 3 chnical studies. Antimicrob Agents Chemother 54 2119-2124. 

The answer is e. (Hardman, pp 1094—1095.) Penicillins were used in the treatment of meningitis because of their ability to pass across an inflamed blood-brain barrier. The third-generation cephalosporin, ceftriaxone, is preferred because it is effective against P-lactamase producing strains of H. influenzae that may cause meningitis in children. 

Amoxycillin is also used in combination with clavulanate potassium. The formulation of amoxycillin with clavulanic acid protects amoxycillin from degradation by beta lactamase enzymes and effectively extends the antibiotic spectrum of amoxycillin to include P lactamase producing bacteria normally resistant to amoxycillin and other betalactam antibiotics. 

It progressively inhibits a wide variety of P-lactamases produced by gram positive and negative organisms and is obtained from Streptomyces clavuligerus. It has no antibacterial activity of its own. 

Many bacteria produce a p-lactamase or penicillinase which opens the (3-lactam ring rendering some p-lactams ineffective. The problem of p-lactamase-producing bacteria can, in part, be overcome by the addition of a p-lactamase inhibitor such as clavulanic acid (as in co-amoxiclav). 

Oral administration twice daily. Well absorbed. Active against p-lactamase-producing organisms. 

Correct answer = B. The fluoroquinolones do not have sufficient activity against S- pneumoniae to be effective. Since they are not p-lac-tams, the fluoroquinolones are effective in treating UTIs caused by p-lactamase-producing organisms. Fluoroquinolones are also indicated for treatment of the other infections listed. 

Amoxicillin/clavulanate and ampicillin/sulbactam are useful for treating lower respiratory infections, otitis media, and sinusitis caused by p-lactamase-producing strains of H. influenzae (see Table 11-3). They are also... 

An important mechanism of acqnired resistance to cephalosporins is drug inactivation by P-lactamases to which the cephalosporins have variable snsceptibility. For example, the P-lactamases produced by S. aureus are considered tme penicillinases and do not affect the cephalosporins. Thus the cephalosporins are nsnally active against penicillinase-producing 5. aureus. In contrast, gram-negative bacteria produce p-lactamases that inactivate many of the cephalosporins. 

Penicillanic acid derivatives are synthetically produced P-lactamase inhibitors. Penicillanic acid sulphone (Fig. 10.6D) protects ampicillin from hydrolysis by staphylococcal P-lactamase and some, but not all, of the P-lactamases produced by Gram-negative bacteria, but is less potent than... 

At harvest, the benzylpenicillin is in solution extra-cellularly, together with a range of other metabolites and medium constituents. The first step in downstream processing is to separate the cells from the liquid broth by techniques such as filtration, ultrafiltration or centrifugation. This stage is carried out under conditions that avoid contamination with P-lactamase-producing microorganisms which could lead to serious or total loss of product. 

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