scholarly journals Emerging Treatment Options for Multi-Drug-Resistant Bacterial Infections

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 519
Author(s):  
Roberto Giurazza ◽  
Maria Civita Mazza ◽  
Roberto Andini ◽  
Pasquale Sansone ◽  
Maria Caterina Pace ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Treatment Options ◽  
Resistance Mechanisms ◽  
Antimicrobial Treatment ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Gram Positive ◽  
Strict Adherence ◽  
Gram Negative ◽  
Gram Positive Cocci

Antimicrobial resistance (AMR) remains one of the top public health issues of global concern. Among the most important strategies for AMR control there is the correct and appropriate use of antibiotics, including those available for the treatment of AMR pathogens. In this article, after briefly reviewing the most important and clinically relevant multi-drug-resistant bacteria and their main resistance mechanisms, we describe the emerging antimicrobial options for both MDR Gram-positive cocci and Gram-negative bacilli, including recently marketed agents, molecules just approved or under evaluation and rediscovered older antibiotics that have regained importance due to their antimicrobial spectrum. Specifically, emerging options for Gram-positive cocci we reviewed include ceftaroline, ceftobiprole, tedizolid, dalbavancin, and fosfomycin. Emerging treatment options for Gram-negative bacilli we considered comprise ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, aztreonam-avibactam, minocycline, fosfomycin, eravacycline, plazomicin, and cefiderocol. An exciting scenario is opening today with the long awaited growing availability of novel molecules for the treatment of AMR bacteria. Knowledge of mechanisms of action and resistance patterns allows physicians to increasingly drive antimicrobial treatment towards a precision medicine approach. Strict adherence to antimicrobial stewardship practices will allow us to preserve the emerging antimicrobials for our future.

scholarly journals The Burden of the Serious and Difficult-to-Treat Infections and a New Antibiotic Available: Cefiderocol

2021 ◽  
Vol 11 ◽  
Author(s):  
Yasaman Taheri ◽  
Nataša Joković ◽  
Jelena Vitorović ◽  
Oliver Grundmann ◽  
Alfred Maroyi ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Antimicrobial Treatment ◽  
Bacterial Cells ◽  
Gram Negative ◽  
Pubmed Database ◽  
Severe Infections ◽  
Unique Cell

Background: Infection is a disease that can occur due to the entrance of a virus, bacteria, and other infectious agents. Cefiderocol is innovative cephalosporin drug that belongs to a special class of antibiotics, sideromycins, which are taken up by bacterial cells through active transport. The unique cell entry and stability to β-lactamases allow cefiderocol to overcome the most common resistance mechanisms in Gram-negative bacteria.Objective: This article aims to highlight the therapeutic efficacy, safety and tolerability of cefiderocol, with a focus on the FDA label.Methods: The pharmacological properties of cefiderocol are also summarized. In this review, we conducted literature research on the PubMed database using the following keywords: “antimicrobial treatment”, “new antibiotic”, “cefiderocol”, “siderophore cephalosporin”; “multidrug-resistant”, “Gram-negative bacilli”, “critically ill patients”; “severe bacterial infections”.Results: There were identified the most relevant data about the pathophysiology of serious bacterial infections, antibacterial mechanism of action, microbiology, mechanisms of resistance, pharmacokinetic and pharmacodynamic properties of cefiderocol.Conclusion: The results highlighted there appeared to be clinical benefit from cefiderocol in the treatment of infections caused by Gram-negative aerobic microorganisms in adult patients with severe infections and limited treatment options.

Resistance to nitrofurantoin is an indicator of extensive drug-resistant (XDR) Enterobacteriaceae

2021 ◽  
Vol 70 (4) ◽  
Author(s):  
Balaram Khamari ◽  
Prakash Kumar ◽  
Bulagonda Eswarappa Pradeep
Keyword(s):  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Treatment Options ◽  
Strong Association ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
Link Type

Introduction. Nitrofurantoin is one of the preferred antibiotics in the treatment of uropathogenic multidrug-resistant (MDR) infections. However, resistance to nitrofurantoin in extensively drug-resistant (XDR) bacteria has severely limited the treatment options. Gap statement. Information related to co-resistance or collateral sensitivity (CS) with reference to nitrofurantoin resistant bacteria is limited. Aim. To study the potential of nitrofurantoin resistance as an indicator of the XDR phenotype in Enterobacteriaceae . Methods. One hundred (45 nitrofurantoin-resistant, 21 intermediately resistant and 34 nitrofurantoin-susceptible) Enterobacteriaceae were analysed in this study. Antibiotic susceptibility testing (AST) against nitrofurantoin and 17 other antimicrobial agents across eight different classes was performed by using the Vitek 2.0 system. The isolates were screened for the prevalence of acquired antimicrobial resistance (AMR) and efflux pump genes by PCR. Results. In total, 51 % of nitrofurantoin-resistant and 28 % of intermediately nitrofurantoin resistant isolates exhibited XDR characteristics, while only 3 % of nitrofurantoin-sensitive isolates were XDR (P=0.0001). Significant co-resistance was observed between nitrofurantoin and other tested antibiotics (β-lactam, cephalosporin, carbapenem, aminoglycoside and tetracycline). Further, the prevalence of AMR and efflux pump genes was higher in the nitrofurantoin-resistant strains compared to the susceptible isolates. A strong association was observed between nitrofurantoin resistance and the presence of bla PER-1, bla NDM-1, bla OXA-48, ant(2) and oqxA-oqxB genes. Tigecycline (84 %) and colistin (95 %) were the only antibiotics to which the majority of the isolates were susceptible. Conclusion. Nitrofurantoin resistance could be an indicator of the XDR phenotype among Enterobacteriaceae , harbouring multiple AMR and efflux pump genes. Tigecycline and colistin are the only antibiotics that could be used in the treatment of such XDR infections. A deeper understanding of the co-resistance mechanisms in XDR pathogens and prescription of AST-based appropriate combination therapy may help mitigate this problem.

Increasing frequency of gram-positive cocci and gram-negative multidrug-resistant bacteria in spontaneous bacterial peritonitis

2013 ◽  
Vol 33 (7) ◽  
pp. 975-981 ◽  
Author(s):  
Alexandra Alexopoulou ◽  
Nikolaos Papadopoulos ◽  
Dimitrios G. Eliopoulos ◽  
Apostolia Alexaki ◽  
Athanasia Tsiriga ◽  
...  
Keyword(s):  
Spontaneous Bacterial Peritonitis ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Bacterial Peritonitis ◽  
Gram Positive Cocci

scholarly journals Treatment of Multi-Drug Resistant Gram-Negative Bacterial Pathogenic Infections

2020 ◽  
Vol 14 (3) ◽  
pp. 1639-1647
Author(s):  
Wardah Mohammad Akram ◽  
Godfred Antony Menezes ◽  
Nida Abbas ◽  
Wasim Ahmad ◽  
Ahmed Mohamed Ahmed
Keyword(s):  
Acinetobacter Baumannii ◽  
Bacterial Infections ◽  
Empirical Therapy ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Review Management ◽  
Emergence Of Resistance ◽  
Novel Therapeutic

The multidrug-resistant Gram-negative bacteria (MDR-GNB) infections in severely infected patients present numerous difficulties in terms of treatment failure where antibiotics cannot arrest such drug resistant bacteria. Based on the patient’s medical history and updated microbiological epidemiology data, an effective empirical treatment remains critical for optimal results to safeguard human health. The aim of this manuscript is to review management of MDR-Gram negative pathogenic bacterial infections. Quick diagnosis and narrow antimicrobial spectrum require rapid and timely diagnosis and effective laboratories in accordance with antimicrobial stewardship (AS) principles. Worldwide, there is an increased emergence of Carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa, and Acinetobacter baumannii. Recently, novel therapeutic options, such as meropenem/vaborbactam, ceftazidime/avibactam, ceftolozane/tazobactam, eravacycline and plazomicin became accessible to effectively counteract severe infections. Optimally using these delays the emergence of resistance to novel therapeutic agents. Further study is required, however, due to uncertainties in pharmacokinetic/pharmacodynamics optimization of dosages and therapeutic duration in severely ill patients. The novel agents should be verified for (i) action on carbapenem resistant Acinetobacter baumannii; (ii) action on CRE of β-lactam/β-lactamase inhibitors dependence on type of carbapenemase; (iii) emergence of resistance to novel antibacterials and dismiss selective pressure promoting development of resistance. Alternative treatments should be approached alike phage therapy or antibacterial peptides. The choice of empirical therapy is complicated by antibiotic resistance and can be combated by accurate antibiotic and their combinations usage, which is critical to patient survival. Noteworthy are local epidemiology, effective teamwork and antibiotic stewardship to guarantee that medications are utilized properly to counter the resistance.

scholarly journals Bacteriological Profile of Neonatal Sepsis in a Tertiary Level Hospital of Nepal

2015 ◽  
Vol 34 (3) ◽  
pp. 175-180 ◽  
Author(s):  
R Khanal ◽  
S Manandhar ◽  
GP Acharya
Keyword(s):  
Developing Countries ◽  
Neonatal Sepsis ◽  
Antimicrobial Agents ◽  
Diffusion Method ◽  
Multiple Drug ◽  
Drug Resistant ◽  
Gram Positive ◽  
Gram Negative ◽  
Multiple Drug Resistant ◽  
Gram Positive Cocci

Introduction: Neonatal sepsis is one of the most common reasons for admission to neonatal units in developing countries. It is also a major cause of mortality in both developed and developing countries. This study was done to determine the bacterial profile causing neonatal sepsis and to assess their susceptibility pattern to various antimicrobial agents. Materials and Methods: A cross-sectional prospective study was conducted in Paropakar Maternity and Women’s Hospital, Kathmandu, Nepal among 340 neonates suspected of neonatal sepsis. Blood culture was performed and organisms were identified with Gram staining and conventional biochemical methods. Antimicrobial susceptibility testing was performed by Kirby-Bauer disk diffusion method according to the Clinical and Laboratory Standards Institute (CLSI). Results: The prevalence rate of neonatal sepsis was 20.3%. Among 340 neonates, 52.17% were males and 47.82% were females. Gram positive cocci were the most predominant isolates (88.40%). Among Gram positive cocci Staphylococcus epidermidis was the most common isolates (72.46%) followed by Staphylococcus aureus (7.24%), Staphylococcus saprophyticus (4.34%) and Enterococcus fecalis (4.34%). Gram negative bacilli were found in 11.60% of the growth positive samples of which E.coli and Klebsiella spp were found in 10.14% and 1.44% respectively. Sensitivity to Amikacin was highest among all types of organisms isolated. Vancomycin and Gentamycin sensitivity was highest for Gram positive and Gram negative organisms respectively. Ampicillin resistance was highest among isolates. Among the 69 isolates 48 were Multiple drug resistant. Conclusion: The predominance of Gram positive cocci particularly Coagulase negative Staphylococci is shown. Empirical antibiotic therapy should be reviewed for Multiple drug resistant strains. DOI: http://dx.doi.org/10.3126/jnps.v34i3.9183 J Nepal Paediatr Soc 2014;34(3):175-180

Efficient Synthesis and Antibacterial Profile of Bis(2-hydroxynaphthalene- 1,4-dione)

2020 ◽  
Vol 20 (2) ◽  
pp. 121-131 ◽  
Author(s):  
Juliana S. Novais ◽  
Aline C. Rosandiski ◽  
Carolina M. de Carvalho ◽  
Letícia S. de Saules Silva ◽  
Lais C. dos S. Velasco de Souza ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Public Health Problem ◽  
In Vitro Toxicity ◽  
Resistant Bacteria ◽  
Gram Positive ◽  
Healthy Human ◽  
Gram Negative ◽  
Methicillin Resistant

Background: Antibacterial resistance is a serious public health problem infecting millions in the global population. Currently, there are few antimicrobials on the market against resistant bacterial infections. Therefore, there is an urgent need for new therapeutic options against these strains. Objective: In this study, we synthesized and evaluated ten Bis(2-hydroxynaphthalene-1,4-dione) against Gram-positive strains, including a hospital Methicillin-resistant (MRSA), and Gram-negative strains. Method: The compounds were prepared by condensation of aldehydes and lawsone in the presence of different L-aminoacids as catalysts in very good yields. The compounds were submitted to antibacterial analysis through disk diffusion and Minimal Inhibitory Concentration (MIC) assays. Result: L-aminoacids have been shown to be efficient catalysts in the preparation of Bis(2- hydroxynaphthalene-1,4-dione) from 2-hydroxy-1,4-naphthoquinones and arylaldehydes in excellent yields of up to 96%. The evaluation of the antibacterial profile against Gram-positive strains (Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 25923, S. epidermidis ATCC 12228) also including a hospital Methicillin-resistant S. aureus (MRSA) and Gram-negative strains (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 and Klebsiella pneumoniae ATCC 4352), revealed that seven compounds showed antibacterial activity within the Clinical and Laboratory Standards Institute (CLSI) levels mainly against P. aeruginosa ATCC 27853 (MIC 8-128 µg/mL) and MRSA (MIC 32-128 µg/mL). In addition, the in vitro toxicity showed all derivatives with no hemolytic effects on healthy human erythrocytes. Furthermore, the derivatives showed satisfactory theoretical absorption, distribution, metabolism, excretion, toxicity (ADMET) parameters, and a similar profile to antibiotics currently in use. Finally, the in silico evaluation pointed to a structure-activity relationship related to lipophilicity for these compounds. This feature may help them in acting against Gram-negative strains, which present a rich lipid cell wall selective for several antibiotics. Conclusion: Our data showed the potential of this series for exploring new and more effective antibacterial activities in vivo against other resistant bacteria.

scholarly journals Rapid antimicrobial susceptibility testing on positive blood cultures through an innovative light scattering technology: performances and turnaround time evaluation

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Lidvine Boland ◽  
Corentin Streel ◽  
Hélène De Wolf ◽  
Hector Rodriguez ◽  
Alexia Verroken
Keyword(s):  
Light Scattering ◽  
Antimicrobial Susceptibility ◽  
Susceptibility Testing ◽  
Turnaround Time ◽  
Blood Cultures ◽  
Antimicrobial Susceptibility Testing ◽  
Resistant Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Cocci

Abstract Background A bacteremia diagnosis with speeded-up identification and antimicrobial susceptibility testing (AST) is mandatory to adjust empirical broad-spectrum antibiotherapy and avoid the emergence of multi-resistant bacteria. Alfred 60AST (Alifax, Polverara, PD, Italy) is an innovative automated system based on light scattering measurements allowing direct AST from positive blood cultures with rapid results. In this study we aimed to evaluate the system’s performances and turnaround time (TAT) compared to routine AST. Methods The study was conducted during 2 non-consecutive 3-month periods at the microbiology laboratory of the Cliniques universitaires Saint-Luc. All blood cultures detected positive in the 0 AM–10 AM time frame with a pure Gram-positive cocci or Gram-negative bacilli stain were included for Alfred 60AST testing. Two customized EUCAST antibiotic panels were set up composed of 1) a “Gram-negative” panel including cefuroxime, ceftazidime Enterobacteriaceae, piperacillin-tazobactam Enterobacteriaceae, ciprofloxacine, and ceftazidime Pseudomonas 2) a “Gram-positive” panel including cefoxitin Staphylococcus aureus, cefoxitin coagulase-negative (CNS) Staphylococci and ampicillin Enterococci. Categorical agreement (CA), very major errors (VME), major errors (ME), minor errors (mE) and TAT to Alfred 60AST results were calculated in comparison with AST results obtained from direct testing on positive blood cultures with the Phoenix system (Becton Dickinson, Franklin Lakes, NJ, USA). Results Five hundred seventy and one hundred nine antibiotics were evaluated on respectively 166 Gram-negative bacilli and 109 Gram-positive cocci included in the studied population. During the first study period regarding Gram-negative strains a CA of 89.5% was obtained with a high rate of VME (19 and 15.4% respectively) for cefuroxime and piperacillin-tazobactam Enterobacteriaceae. Considering this, Alifax reviewed these antibiotics’ formulations improving Gram-negative bacilli total CA to 92.2% with no VME during the second study period. For Gram-positive cocci, total CA was 88.1% with 2.3% VME, 13.8% ME (mainly cefoxitin CNS) and 12% mE rates both study periods combined. Median TAT to AST results was 5 h with Alfred versus 12 h34 with Phoenix. Conclusion The Alfred 60AST system shows correct yet improvable microbiological performances and a major TAT reduction compared to direct automated AST testing. Clinical studies measuring the impact of the approach on antibiotic management of patients with bacteremia are recommended.

scholarly journals Synthetic molecular evolution of host cell-compatible, antimicrobial peptides effective against drug-resistant, biofilm-forming bacteria

2020 ◽  
Vol 117 (15) ◽  
pp. 8437-8448 ◽  
Author(s):  
Charles G. Starr ◽  
Jenisha Ghimire ◽  
Shantanu Guha ◽  
Joseph P. Hoffmann ◽  
Yihui Wang ◽  
...  
Keyword(s):  
Molecular Evolution ◽  
Antimicrobial Peptides ◽  
Host Cell ◽  
Host Cells ◽  
Resistant Bacteria ◽  
Antibiofilm Activity ◽  
Drug Resistant ◽  
Gram Positive ◽  
Gram Negative

Novel classes of antibiotics and new strategies to prevent and treat infections are urgently needed because the rapid rise in drug-resistant bacterial infections in recent decades has been accompanied by a parallel decline in development of new antibiotics. Membrane permeabilizing antimicrobial peptides (AMPs) have long been considered a potentially promising, novel class of antibiotic, especially for wound protection and treatment to prevent the development of serious infections. Yet, despite thousands of known examples, AMPs have only infrequently proceeded as far as clinical trials, especially the chemically simple, linear examples. In part, this is due to impediments that often limit their applications in vivo. These can include low solubility, residual toxicity, susceptibility to proteolysis, and loss of activity due to host cell, tissue, and protein binding. Here we show how synthetic molecular evolution can be used to evolve potentially advantageous antimicrobial peptides that lack these impediments from parent peptides that have at least some of them. As an example of how the antibiotic discovery pipeline can be populated with more promising candidates, we evolved and optimized one family of linear AMPs into a new generation with high solubility, low cytotoxicity, potent broad-spectrum sterilizing activity against a panel of gram-positive and gram-negative ESKAPE pathogens, and antibiofilm activity against gram-positive and gram-negative biofilms. The evolved peptides have these activities in vitro even in the presence of concentrated host cells and also in vivo in the complex, cell- and protein-rich environment of a purulent animal wound model infected with drug-resistant bacteria.

scholarly journals In VitroAntibacterial Activity of Modithromycin, a Novel 6,11-Bridged Bicyclolide, against Respiratory Pathogens, Including Macrolide-Resistant Gram-Positive Cocci

2011 ◽  
Vol 55 (4) ◽  
pp. 1588-1593 ◽  
Author(s):  
Takafumi Sato ◽  
Kazuhiro Tateda ◽  
Soichiro Kimura ◽  
Morihiro Iwata ◽  
Yoshikazu Ishii ◽  
...  
Keyword(s):  
Efflux Pump ◽  
Resistance Mechanisms ◽  
Respiratory Pathogens ◽  
Gram Positive ◽  
Gram Negative ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Medical Facilities ◽  
Gram Positive Cocci

ABSTRACTThein vitroactivities of modithromycin against Gram-positive and -negative respiratory pathogens, including macrolide-resistant cocci with different resistance mechanisms, were compared with those of other macrolide and ketolide agents. MICs were determined by the broth microdilution method. All 595 test strains used in this study were isolated from Japanese medical facilities. Theerm(ribosome methylase) and/ormef(efflux pump) gene, which correlated with resistance to erythromycin as well as clarithromycin and azithromycin, was found in 81.8%, 21.3%, and 23.2% ofStreptococcus pneumoniae,Streptococcus pyogenes, and methicillin-susceptibleStaphylococcus aureus(MSSA) strains, respectively. Modithromycin showed MIC90s of 0.125 μg/ml against these three cocci, including macrolide-resistant strains. In particular, the MIC of modithromycin againstermB-carryingS. pyogeneswas ≥32-fold lower than that of telithromycin. The activities of modithromycin as well as telithromycin were little affected by the presence ofmefAormefEin both streptococci. Against Gram-negative pathogens, modithromycin showed MIC90s of 0.5, 8, and 0.031 μg/ml againstMoraxella catarrhalis,Haemophilus influenzae, andLegionellaspp., respectively. The MICs of modithromycin againstM. catarrhalisandH. influenzaewere higher than those of telithromycin and azithromycin. However, modithromycin showed the most potent anti-Legionellaactivity among the macrolide and ketolide agents tested. These results suggested that the bicyclolide agent modithromycin is a novel class of macrolides with improved antibacterial activity against Gram-positive cocci, including telithromycin-resistant streptococci and intracellular Gram-negative bacteria of theLegionellaspecies.

scholarly journals Bacteriology of diabetic foot infections and their antibacterial susceptibility

2018 ◽  
Vol 6 (10) ◽  
pp. 3276
Author(s):  
Alex Aiswariya ◽  
Kalagara Pavani ◽  
Bhanudas Surpam Rajendra
Keyword(s):  
Diabetic Foot ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Gram Positive ◽  
Gram Negative ◽  
Clinical Specimens ◽  
Antimicrobial Susceptibility Pattern ◽  
Diabetic Foot Infections ◽  
Microbiological Techniques ◽  
Gram Positive Cocci

Background: Diabetic foot infections are the most common bacterial infections encountered in patients with diabetes mellitus and remain the leading complication requiring frequent hospitalization.  Hence, this study was carried out to determine the prevalence of bacteria in diabetic foot infections and their antibiogram which can help to inform therapeutic choices.Methods: A prospective study conducted on clinical specimens taken from patients with diabetic foot infections, over 3 years duration. The clinical specimens were processed by using the standard microbiological techniques. The antimicrobial susceptibility pattern was studied by the Kirby-Bauer disc diffusion method.Results: Among 103 cases studied, 97 were culture positive. Out of these specimens, 25 (25.77%) had monomicrobial flora and 72 (74.23%) had polymicrobial flora. A total of 176 bacteria were obtained which include 62 gram positive cocci and 114 gram negative bacilli. All gram negative bacilli showed good sensitivity to imipenem (97.30%), followed by cefaperazone sulbactam (81.98%), piperacillin-tazobactam (75.68%) and amikacin (72.97%). All gram positive cocci remained 100% sensitive to Vancomycin and Linezolid followed by clindamycin (not tested for Enterococci Spp.) and gentamicin  in a range of  91.43 % to 72.88%. The prevalence of multidrug resistant organisms among aerobic isolates were 59.66%.Conclusions: Diabetic foot infections are polymicrobial. Pseudomonas aeruginosa and Staphylococus aureus were the most common isolates. The most sensitive antibiotics are imipenem for gram negative bacilli while vancomycin and linezolid were effective for gram positive cocci. The antibiogram of isolates will be helpful in determining the drugs for the empirical treatment of diabetic foot infection.

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