Penicillin concentration

Sampling is essential to monitor the amount of growth, the running levels of key nutrients and the penicillin concentration. It is necessary also to check that there has been no contamination by unwanted microorganisms. 

Figure 2.11 Reported concentrations of various PPCPs in treated potable water by several research groups. So far reported are the analgesic (1 = naproxen), antihypertensive (2 = clofibric acid, 3 = dehydronifedipine, 4 = gemfibrozil), reproductive (5 = ethinyl estradiol, 6 = nor-ethindrone), antineoplasts (7 = metyhotrexate, 8 = bleomycin), sedatives (9 = carbamazepine, 10 = diazepam), and antimicrobials (11 = penicillin). Concentrations compiled from Boyd et al. (2003) and Collier (2007).

Penicillin concentrations in most tissues are equal to those in serum. Penicillin is also excreted into sputum and milk to levels 3-15% of those in the serum. Penetration into the eye, the prostate, and the central nervous system is poor. However, with active inflammation of the meninges, as in bacterial meningitis, penicillin concentrations of 1-5 mcg/mL can be achieved with a daily parenteral dose of 18-24 million units. These concentrations are sufficient to kill susceptible strains of pneumococci and meningococci. 

Fig. 3 Mean plasma penicillin concentration-time curves after 20,000 lU of procaine penicillin g/kg was administered to 5 animals (4 horses, 1 pony) at 5 different sites. (From Ref.P l.)...

Fig. 2.9 Mean plasma penicillin concentration-time curves after 20 000IU of procaine penicillin G per kilogram was administered to five animals (four horses and one pony) at five different sites. (Reproduced with permission from Firth et al. (1986).)...

Two new mechanisms of resistance to P-lactams have been reviewed. The "tolerant" S, aureus strains are Inhibited by low penicillin concentrations, but not by high concentrations, probably due to an excess of an inhibitor of autolysln. Enz3nne preparations, derived from Infected, human inflammatory exudate, were found to inactivate several 3-lactams but not other types of antibiotics. ... 

Olsson (1988) obtained a pH signal which was linearly dependent on penicillin concentration by using a penicillinase reactor in an FIA manifold. The linearity was due to complete substrate hydrolysis in the reactor and an almost constant buffer capacity of the carrier stream. To exclude disturbances from varying sample pH the penicillin concentration was calculated as the difference between the response with and without hydrolysis. 

The potential change is proportional to the logarithm of the penicillin concentration. Solid state fluoride or iodide selective electrodes have been employed for the biosensing of glucose or amino acids. These transducers measure the decreasing activity of iodide or fluoride (upon their reaction with the peroxide product). 

Probenecid was developed for the purpose of delaying the excretion of penicillin, and it still is used as an adjuvant to prolong penicillin concentrations in patients being treated for specific infections (e.g., syphilis) or in cases where penicillin resistance may be an issue (see Chapter 44). 

Figure 9.16 The correlation of blood penicillin concentrations at 0.5 h in fasting subjects following the oral administration of three different penicillin V salts (potassium penicillin V, calcium penicillin V and penicillin V) with the in v/trorates of dissolution. Line YvsX is a plot of average plasma penicillin concentration at 0.5 h versus penicillin V in solution after 10 min at pH 2.0. Line Y vs X is average (AUC) versus penicillin V in solution after 10 min at pH 2.0. Line Y vs X is average (ADC) versus penicillin V in solution after 10 min at pH 8.0. In each case, the points from left to right refer to penicillin V, calcium penicillin V and potassium penicillin V. (Juncher ef o/., 1957).

The OAT family of transporters can be inhibited by probenecid. If a substrate of this family of transporters, such as penicillin, is administered concomitantly with probenecid, the dmg can have decreased renal secretion, with a resulting increase in the plasma penicillin concentration. Cimetidine is an inhibitor of members of the OAT, organic cation transporter (OCT) and OATP families of transporters This inhibition has been shown to result in a decrease in the renal excretion of substrates such as procainamide and levofloxacin, resulting in increased plasma concentrations of these dmgs. 

Penicillin is determined by cleaving the amide bond of the jS-lactame ring with penicillase to produce penicilloic acid. This acid is detectable by a pH electrode covered with a thin film of penicillase and the biosensor produced was used to monitor penicillin concentration in many different fermentation broths. 

Prefermenter I 2 Prefermenter II 3 Production fermenter 4 Cooling vessel 5 Storage tank for penicillin concentrate 6 Mixing vessel 7 Dewatering vessel 8 Precipitation vessel... 

The kinetics of induction in B. cereus at different penicillin concentrations [Csanyi, 29] show a similar time course, with the maximum specific activity at the same time (Fig. 5). This was interpreted (Section 111, A, 7, a) to show either that induction produces a continuing destruction of the repressor or that synthesis of the repressor is also regulated by the level of induction. In either case, it suggests that there is not a quantitative equivalence between the penicillin stimulus and the... 

Prepare a second series of twelve tubes by adding 0.5 ml. of the assay medium to all but 1. This rack may be labeled as the standard series. Deliver 0.5 ml. (i. e., 5 units) of penicillin standard solution to tubes 1 and 2. Mix the contents of tube 2 and prepare two-fold serial dilutions through tube 12, exactly as was done for the preparation of the sample dilution series." Tubes in the standard rack will then have the following penicillin concentrations (in units per tube) 6.0, 2.5,1.25,0.625, 0.312, 0.156,0.078, 0.039, 0.019, 0.009, 0.0045, and 0.0022. 

Incubate both racks of tubes and the control tube at 37 C. for 18 hours and record the end point for each series. The greatest sample dilution causing test organism inhibition multiplied by the lowest penicillin concentration which inhibits gives the approximate penicilhn concentration of the sample. 

The rate of penicillin hydrolysis is assumed to be first order in the penicillin concentration ... 

Figure 17.6 shows the penicillin concentration in response to the feed strategy. It can be seen that the penicillin production starts when the substrate concentration has reached low levels, in the proximity of the substrate concentration for maximum production rate... 

In this case, the model consists of Eqns. (17.16), (17.12)-(17.15) and the equations for the kinetics, Eqns. (17.1), (17.4), (17.7) and (17.8). The feed rate is 0.17 1/h and the initial conditions are given in Table 17.2. Figure 17.9 shows the reactor penicillin concentration for various values of the reactor substrate feed rate using the initial conditions from Table 17.2. 

Fig. 17.9. Reactor penicillin concentration as a function of the feed rate.

Starting with a steady-state feed rate of 0.17 1/h, the dynamic responses for a small change in the feed of-10% are shown in Figs. (17.10)-(17.12). Figure (17.10) shows the response of the biomass concentration, Fig. (17.11) shows the response of the substrate concentration and Fig. (17.12) the response of the penicillin concentration. 

Fig. 17.12. Penicillin concentration response to a negative feed change.

As can be seen from Eqns. (17.33), (17.29) and (17.23), the resporrse of the penicillin concentration Cp to a change in the feed rate is a combination of a first-order response (Eqn. (17.33)), followed by the effects of second and third-order resporrse. Eqrration (17.33) also shows that the immediate effect of will be in opposite direction, which means that Cp will initially decrease when Ft increases. The long-term effect is determined by a combination of the process gains that were defined. 

Since the process operates at a feed rate where the penicilhn concentration is maximal (Fig. 17.9), any feed change will lead to a decrease in penicillin concentration. When the feed rate is decreased, the dilution effect decreases, hence the concentration will initially increase. Thus in this case an inverse response would result. If the feed rate increases, the dilution increases, leading to an initially lower penicillin concentration. Also the long-term effect is a lower corKentration, hence an irrverse response is not expected. 

Another interesting feature that can be seen from the linearized model is, that there is only one major time constant in the system, even though there are two interacting balances, the interaction between the biomass and substrate. The response of the penicillin concentration to the feed flow is primarily determined by the first-order path from Fi to Cp, which has a time constant of 46.1 h. This time constant is determined primarily by the kinetic constant kj, for the hydrolysis reaction, as can be seen from Eqn. (17.31), since F/F, = 588.2 and Hky, = 50.0. 

Figure 17.13 shows the response of the penicillin concentration to a +10% change in the feed rate. 

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