Staphylococcus aureus has been an exceptionally successful pathogen, which is still relevant in modern age-medicine due to its adaptability and tenacity. This bacterium may be a causative agent in a plethora of infections, owing to its abundance (in the environment and in the normal flora) and the variety of virulence factors that it possesses. Methicillin-resistant S. aureus (MRSA) strains—first described in 1961—are characterized by an altered penicillin-binding protein (PBP2a/c) and resistance to all penicillins, cephalosporins, and carbapenems, which makes the β-lactam armamentarium clinically ineffective. The acquisition of additional resistance determinants further complicates their eradication; therefore, MRSA can be considered as the first representative of multidrug-resistant bacteria. Based on 230 references, the aim of this review is to recap the history, the emergence, and clinical features of various MRSA infections (hospital-, community-, and livestock-associated), and to summarize the current advances regarding MRSA screening, typing, and therapeutic options (including lipoglycopeptides, oxazolidinones, anti-MRSA cephalosporins, novel pleuromutilin-, tetracycline- and quinolone-derivatives, daptomycin, fusidic acid, in addition to drug candidates in the development phase), both for an audience of clinical microbiologists and infectious disease specialists.
The emergence and spread of antibiotic-resistant pathogens is a major public health issue, which requires global action of an intersectoral nature. Multidrug-resistant (MDR) pathogens—especially “ESKAPE” bacteria—can withstand lethal doses of antibiotics with various chemical structures and mechanisms of action. Pharmaceutical companies are increasingly turning away from participating in the development of new antibiotics, due to the regulatory environment and the financial risks. There is an urgent need for innovation in antibiotic research, as classical discovery platforms (e.g., mining soil Streptomycetes) are no longer viable options. In addition to discovery platforms, a concept of an ideal antibiotic should be postulated, to act as a blueprint for future drugs, and to aid researchers, pharmaceutical companies, and relevant stakeholders in selecting lead compounds. Based on 150 references, the aim of this review is to summarize current advances regarding the challenges of antibiotic drug discovery and the specific attributes of an ideal antibacterial drug (a prodrug or generally reactive compound with no specific target, broad-spectrum antibacterial activity, adequate penetration through the Gram-negative cell wall, activity in biofilms and in hard-to-treat infections, accumulation in macrophages, availability for oral administration, and for use in sensitive patient groups).
Anaerobic bacteria have pivotal roles in the microbiota of humans and they are significant infectious agents involved in many pathological processes, both in immunocompetent and immunocompromised individuals. Their isolation, cultivation and correct identification differs significantly from the workup of aerobic species, although the use of new technologies (e.g., matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, whole genome sequencing) changed anaerobic diagnostics dramatically. In the past, antimicrobial susceptibility of these microorganisms showed predictable patterns and empirical therapy could be safely administered but recently a steady and clear increase in the resistance for several important drugs (β-lactams, clindamycin) has been observed worldwide. For this reason, antimicrobial susceptibility testing of anaerobic isolates for surveillance purposes or otherwise is of paramount importance but the availability of these testing methods is usually limited. In this present review, our aim was to give an overview of the methods currently available for the identification (using phenotypic characteristics, biochemical testing, gas-liquid chromatography, MALDI-TOF MS and WGS) and antimicrobial susceptibility testing (agar dilution, broth microdilution, disk diffusion, gradient tests, automated systems, phenotypic and molecular resistance detection techniques) of anaerobes, when should these methods be used and what are the recent developments in resistance patterns of anaerobic bacteria.
Pseudomonas aeruginosa is the most frequent cause of infection among non-fermenting Gram-negative bacteria, predominantly affecting immunocompromised patients, but its pathogenic role should not be disregarded in immunocompetent patients. These pathogens present a concerning therapeutic challenge to clinicians, both in community and in hospital settings, due to their increasing prevalence of resistance, and this may lead to prolonged therapy, sequelae, and excess mortality in the affected patient population. The resistance mechanisms of P. aeruginosa may be classified into intrinsic and acquired resistance mechanisms. These mechanisms lead to occurrence of resistant strains against important antibiotics—relevant in the treatment of P. aeruginosa infections—such as β-lactams, quinolones, aminoglycosides, and colistin. The occurrence of a specific resistotype of P. aeruginosa, namely the emergence of carbapenem-resistant but cephalosporin-susceptible (Car-R/Ceph-S) strains, has received substantial attention from clinical microbiologists and infection control specialists; nevertheless, the available literature on this topic is still scarce. The aim of this present review paper is to provide a concise summary on the adaptability, virulence, and antibiotic resistance of P. aeruginosa to a readership of basic scientists and clinicians.
Multidrug resistance (MDR) has appeared in response to selective pressures resulting from the incorrect use of antibiotics and other antimicrobials. This inappropriate application and mismanagement of antibiotics have led to serious problems in the therapy of infectious diseases. Bacteria can develop resistance by various mechanisms and one of the most important factors resulting in MDR is efflux pump-mediated resistance. Because of the importance of the efflux-related multidrug resistance the development of new therapeutic approaches aiming to inhibit bacterial efflux pumps is a promising way to combat bacteria having over-expressed MDR efflux systems. The definition of an efflux pump inhibitor (EPI) includes the ability to render the bacterium increasingly more sensitive to a given antibiotic or even reverse the multidrug resistant phenotype. In the recent years numerous EPIs have been developed, although so far their clinical application has not yet been achieved due to their in vivo toxicity and side effects. In this review, we aim to give a short overview of efflux mediated resistance in bacteria, EPI compounds of plant and synthetic origin, and the possible methods to investigate and screen EPI compounds in bacterial systems.
Background and Objective: Urinary tract infections (UTIs) are common in human medicine, affecting large patient populations worldwide. The principal cause of UTIs is uropathogenic Escherichia coli (UPEC) and Klebsiella, both in community and nosocomial settings. The assessment of local data on prevalence and resistance is essential to evaluate trends over time and to reflect on the national situation, compared to international data, using the methods of analytical epidemiology. Materials and Methods: The aim of this study was to assess resistance trends and epidemiology of UTIs caused by E. coli and Klebsiella species in inpatients and outpatients at a tertiary-care hospital in Hungary, using microbiological data. To evaluate resistance trends, several antibiotics were chosen as indicator drugs, based on local utilization data. Results: E. coli was the most prevalent isolate, representing 56.75 ± 4.86% for outpatients and 42.29 ± 2.94% for inpatients. For E. coli, the ratio of resistant strains for several antibiotics was significantly higher in the inpatient group, while in Klebsiella, similar trends were only observed for gentamicin. Extended-spectrum β-lactamase (ESBL)-producing isolates were detected in 4.33–9.15% and 23.22–34.22% from outpatient, 8.85–38.97% and 10.89–36.06% from inpatient samples for E. coli and Klebsiella, respectively. Conclusions: Resistance developments in common UTI pathogens (especially to fosfomycin, sulfamethoxazole-trimethoprim, fluoroquinolones, and 3rd generation cephalosporins), seriously curb therapeutic options, especially in outpatient settings.
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