scholarly journals Chemotherapy and Mechanisms of Action of Antimicrobial Agent

Author(s):  
Rahman Laibi Chelab

Pseudomonas aeruginosa is a widespread opportunistic pathogen that causes bloodstream, urinary tract, burn wounds infections and is one of the largest pathogens that infect cystic fibrosis patients’ airways and can be life-threatening for P. aeruginosa infections. In addition, P. aeruginosa remains one of the most significant and difficult nosocomial pathogens to handle. Increasingly, multi-drug resistance (MDR) strains are identified and the option of therapy is often very limited in these cases, particularly when searching for antimicrobial combinations to treat serious infections. The fact that no new antimicrobial agents are active against the MDR strains of P. aeruginosa is an additional matter of concern. In recent decades, bacterial drug resistance has increased, but the rate of discovery of new antibiotics has decreased steadily. The fight for new, powerful antibacterial agents has therefore become a top priority. This chapter illustrates and explores the current state of several innovative therapeutic methods that can be further discussed in clinical practice in the treatment of P. aeruginosa infections.

Author(s):  
Namita A., Raytekar, ◽  
Meghna R. Choudhari ◽  
Sonali Das

Background: Pseudomonas aeruginosa (P. aeruginosa) considered as an opportunistic pathogen which can be isolated from various kinds of infection. The risk of emergence of antibiotic resistance is based on different antibiotic treatments. Antibiotic resistance and flexibility to adapt changing environment renders the pathogens a matter of concern in hospital acquired infections. Changing pattern of antimicrobial resistance pose challenge in treating pyogenic infections, hence periodical monitoring of bacterial profile and their antibiotic susceptibility pattern is important. This study deals with the infectious and drug resistance nature of P. aeruginosa with effectiveness of antimicrobial agents against it.Methods: Present study was conducted in Centre for Biotechnology, Pravara Institute of Medical Sciences, Loni, Maharashtra, India. A total of 763 pus samples were received in the bacteriology section of department of microbiology, rural medical college, Loni from the various wards of Pravara Rural Hospital. The colonial morphology and identification was done as per standard microbiology procedures. Antibiogram testing was done as per Kirby Bauer disc diffusion method.Results: Out of 763 pus samples 154 were Pseudomonas aeruginosa thus showing 20.19% prevalence. In this study, it was observed that isolates were sensitive to Ciprofloxacin (76.63%) followed by Amikacin. However, showed 90.90 % resistant to Cefazolin followed by Co-trimoxazole 75.97% was observed. Multi drug resistance (MDR) strain 68.83% (N=106) was detected from 154 isolates strains of Pseudomonas aeruginosa. Prevalent resistance pattern was found to be GENr, AKr, CAZr, CZr, COTr for 10 (9.43%) isolates followed by GENr, CAZr, CZr, MRPr, COTr, CIPr for 9 (8.49%) isolates.Conclusions: Present study focused on antibiotic resistance pattern of P. aeruginosa from pus sample. This study contributes in understanding the emergence of MDR strains which can be considered for judicial usage of antibiotics in hospital settings. 


2001 ◽  
Vol 45 (7) ◽  
pp. 1982-1989 ◽  
Author(s):  
Adriana E. Rosato ◽  
Bonnie S. Lee ◽  
Kevin A. Nash

ABSTRACT Corynebacterium jeikeium is an opportunistic pathogen primarily of immunocompromised (neutropenic) patients. Broad-spectrum resistance to antimicrobial agents is a common feature of C. jeikeium clinical isolates. We studied the profiles of susceptibility of 20 clinical strains of C. jeikeium to a range of antimicrobial agents. The strains were separated into two groups depending on the susceptibility to erythromycin (ERY), with one group (17 strains) representing resistant organisms (MIC > 128 μg/ml) and the second group (3 strains) representing susceptible organisms (MIC ≤ 0.25 μg/ml). The ERY resistance crossed to other members of the macrolide-lincosamide-streptogramin B (MLSb) group. Furthermore, this resistance was inducible with MLSb agents but not non-MLSb agents. Expression of ERY resistance was linked to the presence of an allele of the class X erm genes,erm(X)cj, with >93% identity to other ermgenes of this class. Our evidence indicates that erm(X)cj is integrated within the chromosome, which contrasts with previous reports for the plasmid-associated erm(X) genes found inC. diphtheriae and C. xerosis. In 40% ofC. jeikeium strains, erm(X)cj is present within the transposon, Tn5432. However, in the remaining strains, the components of Tn5432 (i.e., the erm and transposase genes) have separated within the chromosome. The rearrangement of Tn5432 leads to the possibility that the other drug resistance genes have become included in a new composite transposon bound by the IS1249 elements.


Author(s):  
Zahra Davoudi ◽  
Amirhossein Taromchi ◽  
Bahram Kazemi ◽  
Mojgan Bandehpour ◽  
Nariman Mosaffa

Background and Objectives: Immunization is a promising strategy to combat against the life-threatening infections by Multi Drug Resistance Acinetobacter baumannii. In this study, we directed to design and evaluate the efficacy of a recombi- nant multi-epitope protein against this pathogen. Materials and Methods: Epitopes prediction was performed for candidate proteins OmpA and BAM complex (BamA, BamB, BamC, BamD, BamE) from A. baumannii, using immune-informatics tools with high affinity for the human HLA alleles. After expression and purification of the recombinant protein, its functional activity was confirmed by interaction with positive sera. Results: Cloning and expression of the desired multi-epitopes protein were verified. Circular Dichroism study showed the secondary structure and proper refolding of the recombinant protein was achieved and matched with computational predic- tion. There was a significant interaction between designed protein with antibodies presented in ICU patients' and staff's sera. Conclusion: The interaction of the recombinant protein with patients' sera antibodies suggests that it may be a promising determinant protein for immunization against of MDR A. baumannii.


2021 ◽  
Vol 8 (3) ◽  
pp. 230-234
Author(s):  
Naga Sri Latha Bathala ◽  
M Sasidhar ◽  
S Kusuma Bai

CoNS are gaining importance due to increase in resistance rates to betalactam antibiotics and multi drug resistance. Although specific virulence factors are not as clearly established, it seems clear that factors such as bacterial polysaccharide components, and ability to form biofilm are involved in attachment and/or persistence of bacteria on foreign materials. Biofilms usually result in persistent infections that cannot be easily resolved with standard antibiotic treatments; therefore, the biofilm formation ability and the resistance to antimicrobial therapy can be intimately related. A prospective cross-sectional study was done on purely isolated CoNS from various clinical samples from both out patients and inpatients. All the test strains were subjected to antimicrobial susceptibility testing. The ability to produce biofilm was detected by tube adherence method. Among 193 CoNS isolates 156 were from inpatients and 37 were from out patients. Methicillin resistant was seen in 80.31%. Of the total, 40.41% showed moderate biofilm formation by tube adherence method. 23.32% of isolates did not form biofilm. All the isolates from blood samples showed moderate (20/26) and strong (6/26) biofilm formation. Among non biofilm producers 66.67% were MS CoNS isolates and 33.33% were MRCoNS. 94.59% of biofilm producers were MRCoNS and 5.41% were MSCoNS. Production of biofilm was relatively more (1.16) among CoNS isolates of IPD than OPD.  As Coagulase negative Staphylocooci are exhibiting multi drug resistance and are able to form biofilm, these organisms causing a major challenge for the physicians. Hence, such problems can be prevented by detection of biofilm producers and appropriate antibiotic doses modification. The issue of antibiotic resistance among CoNS needs to be addressed through a more rational use of existing antibiotics as well as the development of new antimicrobial agents.


2014 ◽  
Vol 27 (6) ◽  
pp. 573-577 ◽  
Author(s):  
Kurt A. Wargo ◽  
Jonathan D. Edwards

Aminoglycosides are among the oldest antibiotics available to treat serious infections caused by primarily, Gram-negative bacteria. The most commonly utilized parenteral agents in this class include gentamicin, tobramycin and amikacin. Aminoglycosides are concentration-dependent, bactericidal agents that undergo active transport into the cell where they inhibit protein synthesis on the 30S subunit of the bacterial ribosome. As the use of aminoglycosides became more widespread, the toxic effects of these agents, most notably ototoxicity and nephrotoxicity, became more apparent. When other, safer, antimicrobial agents became available, the use of aminoglycosides sharply declined. The development of multi-drug resistance among bacteria has now lead clinicians to reexamine the role of the aminoglycosides in the treatment of serious infections. This review will revisit the mechanism and risk factors for the development of aminoglycoside-induced nephrotoxicity, as well as strategies to prevent patients from developing nephrotoxicity.


Author(s):  
Devin Sindeldecker ◽  
Shaurya Prakash ◽  
Paul Stoodley

Pseudomonas aeruginosa is a Gram-negative, opportunistic pathogen which is involved in numerous infections. It is of growing concern within the field of antibiotic resistant and tolerance and often exhibits multi-drug resistance. Previous studies have shown the emergence of antibiotic resistant and tolerant variants within the zone of clearance of a biofilm lawn after exposure to aminoglycosides. As concerning as the tolerant variant emergence is, there was also a zone of killing (ZOK) immediately surrounding the antibiotic source from which no detectable bacteria emerged or were cultured. In this study, the ZOK was analyzed using both in vitro and in silico methods to determine if there was a consistent antibiotic concentration versus time constraint (area under the curve, (AUC)) which is able to completely kill all bacteria in the lawn biofilms in our in vitro model. Our studies revealed that by achieving an average AUC of 4,372.5 μg*hr/mL, complete eradication of biofilms grown on both agar and hydroxyapatite was possible. These findings show that appropriate antibiotic concentrations and treatment duration may be able to treat antibiotic resistant and tolerant biofilm infections.


2021 ◽  
Vol 7 (10) ◽  
pp. 800
Author(s):  
Zuzana Javorova Rihova ◽  
Lubica Slobodova ◽  
Anna Hrabovska

Candiduria is a common nosocomial infection in hospitalized patients, which may progress into life-threatening candidemia. Successful treatment of urosepsis requires early and effective antifungal therapy, while the available agents within three pharmacological classes each have characteristic pharmacokinetics and side effect profiles. Moreover, treatment of Candida spp. infections is becoming challenging due to increasing multi drug-resistance. Here, we present a case of candidemia resulting from a multi drug-resistant C. glabrata infection of the urinary tract. Due to resistance to fluconazole and a contraindication for amphotericin B, micafungin was used in the treatment, regardless of its unfavorable pharmacokinetic properties. Our study showed that despite the expected low levels in the urinary tract, micafungin was successful in the eradication of C. glabrata allowing full recovery of the patient. Thus, micafungin should be considered in the management of urosepsis caused by sensitive Candida spp.


2021 ◽  
Author(s):  
Riya Mukherjee ◽  
Anjali Priyadarshini ◽  
Ramendra Pati Pandey ◽  
Vethakkani Samuel Raj

Staphylococcus aureus is a Gram-Positive bacteria that are responsible to cause skin infections and also shows toxic shock syndrome. Several antibiotics were given against the S. aureus infections but eventually, the prevalence of multidrug resistance of Staphylococcus aureus started emerging. Since then Methicillin-resistant Staphylococcus aureus strains (MRSA)were very common which causes nosocomial infections. Microorganisms for the need of the survival undergoes mutational changes either in their chromosomal DNA/RNA which confers the resistance. One of the famous examples is the resistance against methicillin in Staphylococcus aureus. The evolution of S. aureus is successful in developing multiple resistant strains. Plasmids are capable of carrying the resistant genes and also several toxic genes. In a recent study, it has been observed that drug resistance genes are located in the R plasmids and they are also responsible in conferring multi drug resistance and induce less utilization of multiple antimicrobial therapy. MRSA was not only resistant to methicillin, studies proved MRSA strains were resistant to macrolides, tetracyclines, chloramphenicol. Resistance to vancomycin was very evidently observed, and its transfer among the population and rising of resistant strains was becoming a major threat globally. The resistance of all these antimicrobial agents against the pathogenic microorganisms are taking a rise in some patients due to prolong use of the antimicrobial agents by these patients. The multi drug resistance has enhanced the mortality and morbidity rate which referred to the infecting agents as the “Super Bugs”. Survival of the microorganisms has increased due to the gradual development of extensive resistance against varied antimicrobial drugs. Possible treatments with combinations are found to be the only hope for infections against S. aureus. Few drugs are in development such as Dalbavancin, Oritavancin, Tigecycline. These are the possible treatments upon which the work is going on to reduce the resistance against the invasive MRSA. This chapter highlights the profiles of Staphylococcus aureus and the resistance patterns along with transmission and the role of the plasmid in transmitting the resistance.


2021 ◽  
Vol 7 (2) ◽  
pp. 296-303
Author(s):  
Saly Amaliacahya Aprilian ◽  
Firdayani Firdayani ◽  
Susi Kusumaningrum

Studi In Silico Senyawa Turunan Sefalosporin dalam Menghambat Aktivitas Bakteri Pseudomonas aeruginosa Infeksi yang diakibatkan oleh bakteri gram-negatif, seperti Pseudomonas aeruginosa telah menyebar luas di seluruh dunia. Hal ini menjadi ancaman terhadap kesehatan masyarakat karena merupakan bakteri yang multi-drug resistance dan sulit diobati. Oleh karena itu, pentingnya pengembangan agen antimikroba untuk mengobati infeksi semakin meningkat dan salah satu yang saat ini banyak dikembangkan adalah senyawa turunan sefalosporin. Penelitian ini melakukan studi mengenai interaksi tiga dimensi (3D) antara antibiotik dari senyawa turunan Sefalosporin dengan penicillin-binding proteins (PBPs) pada P. aeruginosa. Tujuan dari penelitian ini adalah untuk mengklarifikasi bahwa agen antimikroba yang berasal dari senyawa turunan sefalosporin efektif untuk menghambat aktivitas bakteri P. aeruginosa. Struktur PBPs didapatkan dari Protein Data Bank (PDB ID: 5DF9). Sketsa struktur turunan sefalosporin digambar menggunakan Marvins Sketch. Kemudian, studi mengenai interaksi antara antibiotik dan PBPs dilakukan menggunakan program Mollegro Virtual Docker 6.0. Hasil yang didapatkan yaitu nilai rerank score terendah dari kelima generasi sefalosporin, di antaranya sefalotin (-116.306), sefotetan (-133.605), sefoperazon (-160.805), sefpirom (-144.045), dan seftarolin fosamil (-146.398). Infections caused by gram-negative bacteria, such as Pseudomonas aeruginosa, have been spreading worldwide. It is a threat to public health because of its multi-drug resistance and difficulty to treat. Therefore, the demand for developing antimicrobial agents to treat infections is increasing. One of them that is currently under development is cephalosporin derivative compounds. This research studied the three-dimensional (3D) interaction between antibiotics from cephalosporin derivatives and penicillin-binding proteins (PBPs) in P. aeruginosa. This study aimed to clarify whether the cephalosporin derivatives were effective in inhibiting the activity of P. aeruginosa. The PBPs structure was obtained from the Protein Data Bank (PDB ID: 5DF9). The structural sketch of the cephalosporin derivative was drawn using the Marvins Sketch, whereas the study on the interaction between antibiotics and PBPs was carried out using the Mollegro Virtual Docker 6.0 program. The results showed the lowest rerank score from five cephalosporin derivatives, namely cephalotin (-116,306), cephotetan (-133.605), cephoperazone (-160.805), cephpirome (-144.045), and cephtaroline fosamil (-146.398).


1993 ◽  
Vol 56 (6) ◽  
pp. 489-492 ◽  
Author(s):  
LINDA M. KNUDTSON ◽  
PAUL A. HARTMAN

Antibiotic resistance among enterococci and fecal streptococci was examined by testing 149 isolates from pork, water, and clinical material, as well as 50 strains of 13 known species, for resistance to 27 different antimicrobial agents. Tests were performed by using the MicroScan Pos MIC type 6 panels. Pork isolates exhibited less resistance than either water or clinical isolates to most antibiotics, although a larger proportion of pork isolates than others was resistant to tetracycline. Comparisons of antimicrobial-resistance patterns between enterococcal species revealed that Enterococcus faecium was most resistant to β-lactam antimicrobials, especially ampicillin, whereas Enterococcus faecalis seemed to be the most resistant to the synergistic effects of antimicrobial combinations. Vancomycin resistance was observed in one Enterococcus hirae isolate from water. Enterococcal isolates from any of the sources tested did not show multiple resistance to antibiotics (such as gentamicin, ampicillin, streptomycin, and vancomycin) used to treat serious infections caused by gram-positive cocci.


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