Pharmacokinetic/Pharmacodynamic Modeling of Antibiotics
Hartmut Derendorf, Günther Hochhaus in Handbook of Pharmacokinetic/Pharmacodynamic Correlation, 2019
An interesting variation was given by Koenig et al.28,29 A two-compartment body model was used. The dialyzer consisted of regenerated cellulose. In compartment I, a broth solution was circulated in a closed system at a flow rate of 50 ml/min. Antibiotics and bacteria were added to the solution. Compartment II was perfused with dialysis fluid isotonic to the broth used in compartment I. According to the concentration gradient between compartments I and II and the pore size of the capillaries, only the antibiotic diffused from compartment I to compartment II. The model was used to investigate ampicillin activity against various bacteria. It induced a drop in the number of viable pneumococci and meningococci to 103/ml (from 106/ml). The effect of multiple dosing of cefotaxime against Serratia marcescens is shown in Figure 10. After the first dose there is a reduction in the number of viable counts from 106/ml to 2 × 103/ml over 5 h. By 6 to 7 h after the first administration of drug, the bacteria started to regrow. The second dose did not have such a pronounced effect (viable counts dropped from 4 × 104/ml to 5 × 103/Vml). Regrowth had already started after 3 h and the third dose had no appreciable effect. The bacteria became resistant.
Mecillinam (Amdinocillin) and Pivmecillinam
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Pivmecillinam or a pivmecillinam–pivampicillin combination have been compared for the treatment of urinary tract infections in patients with underlying urological abnormalities. Combination therapy was more successful in eradicating urinary pathogens (Igesund and Vorland, 1982; Multicenter Study, 1983; Eriksson et al., 1986). Combination mecillinam and cefoxitin therapy was efficacious for the treatment of complicated urinary tract infections caused by multiply-resistant Serratia marcescens strains (Ward et al., 1983). Pivmecillinam in a single bedtime dose of 5–10 mg/kg appeared satisfactory for long-term prophylaxis to girls with recurrent bacteriuria (Jodal et al., 1989). The markedly enhanced effect obtained when E. coli is exposed to mecillinam in conditions of low osmolality, suggests that it may be advisable to reduce urine osmolality by increased fluid intake when mecillinam is used to treat urinary tract infections (Greenwood, 1976).
In vitro anti-biofilm efficacy of sanguinarine against carbapenem-resistant Serratia marcescens
Published in Biofouling, 2021
Yuting Fu, Wanting Liu, Miao Liu, Jianing Zhang, Min Yang, Ting Wang, Weidong Qian
Serratia marcescens is a Gram-negative opportunistic human pathogen belonging to the family Enterobacteriaceae, which causes hospital-acquired infections and outbreaks in severely immunocompromised or critically ill patients, especially those in intensive care units (ICUs) (Cristina et al. 2019). Furthermore, S. marcescens is known to cause a growing number of severe nosocomial infections, such as urinary tract infections, respiratory tract infections, bacteremia, conjunctivitis, endocarditis, meningitis, and wound infections (Su et al. 2003). S. marcescens may be generally isolated from various samples such as lung, blood, urine, and pus samples as well as from the hospital environment and medical equipment (Khanna et al. 2013). The emergence of carbapenem-resistant S. marcescens (CRSM) can generate intrinsic and/or acquired resistance to antimicrobial agents, and poses an important clinical issue (Nordmann et al. 2011). Carbapenem resistance in S. marcescens has been historically and mainly associated with a specific group of carbapenemases, including class A (mainly KPC), and class B (VIM, NDM, and IMP) (Miao et al. 2018). In recent years, a significant increase in outbreaks associated with extended-spectrum CRSM isolates has been noted in different regions of the world (Merkier et al. 2013).
Plumbagin inhibits quorum sensing-regulated virulence and biofilms of Gram-negative bacteria: in vitro and in silico investigations
Published in Biofouling, 2021
Faizan Abul Qais, Mohammad Shavez Khan, Iqbal Ahmad, Fohad Mabood Husain, Abdulaziz Abdullah Al-kheraif, Mohammed Arshad, Pravej Alam
QS is a bacterial cell-to-cell communication system in which bacteria coordinate the expression of certain sets of genes. Bacteria synthesize signal molecules (autoinducers (AIs)) which are sensed or detected by the bacteria. Once the concentration of AIs reaches the threshold level, bacteria start the expression of QS-controlled genes. The expression of most of the drug-resistant and virulent genes is controlled by QS (Ng and Bassler 2009). Acylated homoserine lactones (AHLs) are the most common AIs in Gram-negative bacteria. In QS of Gram-negative bacteria, AIs are synthesized and diffuse out of the cell; AIs bind with specific receptors to start the expression of QS-controlled genes, and this process continues by a feed-forward loop (Papenfort and Bassler 2016). There are three main QS systems in Pseudomonas aeruginosa: RhlI-RhlR, PQS-MvfR and LasI-LasR (Lee and Zhang 2015). RhlR/RhlI senses C4-HSL and the AIs for the LasR/LasI system is 3O-C12-HSL. Serratia marcescens is an opportunistic Gram-negative bacterial pathogen which is known to cause numerous nosocomial infections, including respiratory tract infection, urinary tract infections and wound infections. The severity of such infection is enhanced by the production of virulence factors that causes damage to the host’s cells (Hejazi and Falkiner 1997).
Enhancing efficacy of existing antibacterials against selected multiple drug resistant bacteria using cinnamic acid-coated magnetic iron oxide and mesoporous silica nanoparticles
Published in Pathogens and Global Health, 2022
Noor Akbar, Muhammad Kawish, Tooba Jabri, Naveed Ahmed Khan, Muhammad Raza Shah, Ruqaiyyah Siddiqui
Among multiple drug resistance (MDR) bacteria, Escherichia coli and Methicillin-resistant Staphylococcus aureus (MRSA) cause several infections including gastroenteritis, meningitis, urinary tract infections (UTIs), skin, respiratory, and other nosocomial infections [11–13]. Pseudomonas aeruginosa being a nosocomial pathogen causes 20% of hospital-acquired infections, bloodstream infections and is prevalent in patients with acute leukemia, burn wounds, cystic fibrosis, and organ transplants [14,15]. Serratia marcescens colonizes the intensive care unit and causes opportunistic infections [16]. A wide spectrum of invasive infections are caused by Klebsiella pneumonia including pneumonia, meningitis, pyogenic liver abscess, UTIs, bloodstream infection, and intra-abdominal infection etc [17]. Streptococcus pneumoniae causes pneumonia in children and has been isolated from patients with purulent pleuritis [18].
Related Knowledge Centers
- Respiratory Tract
- Urinary Tract Infection
- Bacillus
- Infection
- Urinary System
- Gram-Negative Bacteria
- Yersiniaceae
- Facultative Anaerobic Organism
- Hospital-Acquired Infection
- Bloodstream Infections