Antimicrobial substances may be synthetic, semisynthetic, or of natural origin (i.e., from plants and animals). Antimicrobials are considered "miracle drugs" and can determine if an infected patient/animal recovers or dies. However, the misuse of antimicrobials has led to the development of multi-drug-resistant bacteria, which is one of the greatest challenges for healthcare practitioners and is a significant global threat. The major concern with the development of antimicrobial resistance is the spread of resistant organisms. The replacement of conventional antimicrobials by new technology to counteract antimicrobial resistance is ongoing. Nanotechnology-driven innovations provide hope for patients and practitioners in overcoming the problem of drug resistance. Nanomaterials have tremendous potential in both the medical and veterinary fields. Several nanostructures comprising metallic particles have been developed to counteract microbial pathogens. The effectiveness of nanoparticles (NPs) depends on the interaction between the microorganism and the NPs. The development of effective nanomaterials requires in-depth knowledge of the physicochemical properties of NPs and the biological aspects of microorganisms. However, the risks associated with using NPs in healthcare need to be addressed. The present review highlights the antimicrobial effects of various nanomaterials and their potential advantages, drawbacks, or side effects. In addition, this comprehensive information may be useful in the discovery of broad-spectrum antimicrobial drugs for use against multi-drug-resistant microbial pathogens in the near future.
Delivering novel antimycobacterial agents through the pulmonary route using nanoparticle-based systems shows promise for treating diseases like tuberculosis. However, creating dry powder inhaler (DPI) with suitable aerodynamic characteristics while preserving nanostructure integrity and maintaining bioactivity until the active ingredient travels deeply into the lungs is a difficult challenge. We developed DPI formulations containing levofloxacin-loaded solid lipid nanoparticles (SLNs) via spray-drying technique with tailored aerosolization characteristics for effective inhalation therapy. A range of biophysical techniques, including transmission electron microscopy, confocal microscopy, and scanning electron microscopy were used to measure the morphologies and sizes of the spray-dried microparticles that explored both the geometric and aerodynamic properties. Spray drying substantially reduced the particle sizes of the SLNs while preserving their nanostructural integrity and enhancing aerosol dispersion with efficient mucus penetration. Despite a slower uptake rate compared to plain SLNs, the polyethylene glycol modified formulations exhibited enhanced cellular uptake in both A549 and NR8383 cell lines. The percent viability of Mycobacterium bovis had dropped to nearly 0 % by day 5 for both types of SLNs. Interestingly, the levofloxacin-loaded SLNs demonstrated a lower minimum bactericidal concentration (0.25 µg/mL) compared with pure levofloxacin (1 µg/mL), which indicated the formulations have potential as effective treatments for tuberculosis.
28 new pyrrolidine types of compounds as analogues for natural polyhydroxy alkaloids of codonopsinine were evaluated for their anti-MRSA activity using MIC and MBC value determination assay against a panel of S. aureus isolates. One pyrrolidine compound, MFM 501, exhibited good inhibitory activity with MIC value of 15.6 to 31.3 μg/mL against 55 S. aureus isolates (43 MRSA and 12 MSSA isolates). The active compound also displayed MBC values between 250 and 500 μg/mL against 58 S. aureus isolates (45 MRSA and 13 MSSA isolates) implying that MFM 501 has a bacteriostatic rather than bactericidal effect against both MRSA and MSSA isolates. In addition, MFM 501 showed no apparent cytotoxicity activity towards three normal cell lines (WRL-68, Vero, and 3T3) with IC50 values of >625 µg/mL. Selectivity index (SI) of MFM 501 gave a value of >10 suggesting that MFM 501 is significant and suitable for further in vivo investigations. These results suggested that synthetically derived intermediate compounds based on natural products may play an important role in the discovery of new anti-infective agents against MRSA.
The treatment of tuberculosis by chemotherapy is complicated due to multiple drug prescriptions, long treatment duration, and adverse side effects. We report here for the first time an in vitro therapeutic effect of nanocomposites based on para-aminosalicylic acid with zinc layered hydroxide (PAS-ZLH) and zinc-aluminum layered double hydroxides (PAS-Zn/Al LDH), against mycobacteria, Gram-positive bacteria, and Gram-negative bacteria. The nanocomposites demonstrated good antimycobacterial activity and were found to be effective in killing Gram-positive and Gram-negative bacteria. A biocompatibility study revealed good biocompatibility of the PAS-ZLH nanocomposites against normal human MRC-5 lung cells. The para-aminosalicylic acid loading was quantified with high-performance liquid chromatography analysis. In summary, the present preliminary in vitro studies are highly encouraging for further in vivo studies of PAS-ZLH and PAS-Zn/Al LDH nanocomposites to treat tuberculosis.
In an effort to develop new antibacterial drugs, some novel bisindolylmethane derivatives containing Schiff base moieties were prepared and screened for their antibacterial activity. The synthesis of the bisindolylmethane Schiff base derivatives 3-26 was carried out in three steps. First, the nitro group of 3,3'-((4-nitrophenyl)-methylene)bis(1H-indole) (1) was reduced to give the amino substituted bisindolylmethane 2 without affecting the unsaturation of the bisindolylmethane moiety using nickel boride in situ generated. Reduction of compound 1 using various catalysts showed that combination of sodium borohydride and nickel acetate provides the highest yield for compound 2. Bisindolylmethane Schiff base derivatives were synthesized by coupling various benzaldehydes with amino substituted bisindolylmethane 2. All synthesized compounds were characterized by various spectroscopic methods. The bisindolylmethane Schiff base derivatives were evaluated against selected Gram-positive and Gram-negative bacterial strains. Derivatives having halogen and nitro substituent display weak to moderate antibacterial activity against Salmonella typhi, S. paratyphi A and S. paratyphi B.
Natural glycopeptide antibiotics like vancomycin and teicoplanin have played a significant role in countering the threat posed by Gram-positive bacterial infections. The emergence of resistance to glycopeptides among enterococci and staphylococci has prompted the search for second-generation drugs of this class and semi-synthetic derivatives are currently under clinical trials. Antimicrobial resistance among Gram-positive organisms has been increasing steadily during the past several decades and the current development of antibiotics falls short of meeting the needs. Oritavancin (LY-333328 diphosphate), a promising novel second-generation semisynthetic lipoglycopeptide, has a mechanism of action similar to that of other glycopeptides. It has concentration-dependent activity against a variety of Gram-positive organisms specially methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate resistant Staphylococcus aureus (VISA), Streptococcus pneumoniae and vancomycin-resistant enterococcus. It is rapidly bactericidal against many species and in particular for enterococci where vancomycin and teicoplanin are only bacteriostatic even against susceptible strains. The pharmacokinetic profile of oritavancin has not been fully described; however, oritavancin has a long half-life of about 195.4 hours and is slowly eliminated by renal means. Oritavancin is not metabolized by the liver in animals. Oritavancin will most probably be prescribed as a once-daily dose and it demonstrates concentration-dependent bactericidal activity. Oritavancin has demonstrated preliminary safety and efficacy in Phase I and II clinical trials. In a Phase III clinical trial, oritavancin has achieved the primary efficacy end point in the treatment of complicated Gram-positive skin and skin-structure infections. To date, adverse events have been mild and limited; the most common being administration site complaints, headache, rhinitis, dry skin, pain, increases in liver transaminases and accumulation of free cholesterol and phospholipids in phagocytic (macrophages) and nonphagocytic (fibroblast) cells. Oritavancin appears to be a promising antimicrobial alternative to vancomycin (with additional activity against Staphylococcus and Enterococcus resistant to vancomycin) for the treatment of complicated Gram-positive skin and skin-structure infections. Additional clinical data are required to fully explore its use.
Palm kernel oil esters nanoemulsion-loaded with chloramphenicol was optimized using response surface methodology (RSM), a multivariate statistical technique. Effect of independent variables (oil amount, lecithin amount and glycerol amount) toward response variables (particle size, polydispersity index, zeta potential and osmolality) were studied using central composite design (CCD). RSM analysis showed that the experimental data could be fitted into a second-order polynomial model. Chloramphenicol-loaded nanoemulsion was formulated by using high pressure homogenizer. The optimized chloramphenicol-loaded nanoemulsion response values for particle size, PDI, zeta potential and osmolality were 95.33nm, 0.238, -36.91mV, and 200mOsm/kg, respectively. The actual values of the formulated nanoemulsion were in good agreement with the predicted values obtained from RSM. The results showed that the optimized compositions have the potential to be used as a parenteral emulsion to cross blood-brain barrier (BBB) for meningitis treatment.
The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections in intensive care units in Malaysia is significant. Invasive MRSA infections are commonly treated with vancomycin. In clinical practice, the serum vancomycin trough concentration is used as a surrogate marker of vancomycin efficacy. A low concentration of vancomycin may result in less effective therapy and increase the risk of bacterial resistance. We evaluated the relationship between the resolution of MRSA infections and trough concentrations of vancomycin.
In this study, antibacterial characteristic of silver/poly (lactic acid) nanocomposite (Ag/PLA-NC) films was investigated, while silver nanoparticles (Ag-NPs) were synthesized into biodegradable PLA via chemical reduction method in diphase solvent. Silver nitrate and sodium borohydride were respectively used as a silver precursor and reducing agent in the PLA, which acted as a polymeric matrix and stabilizer. Meanwhile, the properties of Ag/PLA-NCs were studied as a function of the Ag-NP weight percentages (8, 16, and 32 wt% respectively), in relation to the use of PLA. The morphology of the Ag/PLA-NC films and the distribution of the Ag-NPs were also characterized. The silver ions released from the Ag/PLA-NC films and their antibacterial activities were scrutinized. The antibacterial activities of the Ag/PLA-NC films were examined against Gram-negative bacteria (Escherichia coli and Vibrio parahaemolyticus) and Gram-positive bacteria (Staphylococcus aureus) by diffusion method using Muller-Hinton agar. The results indicated that Ag/PLA-NC films possessed a strong antibacterial activity with the increase in the percentage of Ag-NPs in the PLA. Thus, Ag/PLA-NC films can be used as an antibacterial scaffold for tissue engineering and medical application.
Antibiotic pouch technique is commonly used due to the high local antibiotic concentration and moist environment for wound healing. We used locally made gentamicin impregnated Plaster of Paris discs in treating wounds with exposed deep structures like tendons and bones. Out of 22 patients treated with this method, 19 completed treatment. Granulation tissue formed quickly and effectively covered the exposed structures. All wounds either healed by secondary intention or became suitable for split skin grafting. Gentamicin impregnated Plaster of Paris disc pouch dressing is safe, cost saving, and effective for management of deep open wounds.
Burkholderia pseudomallei, the causative agent of melioidosis, is endemic in southeast Asia and northern Australia. In recent years, the incidence of melioidosis has increased worldwide. Septic arthritis is a rare but well-recognized manifestation of melioidosis. Patients with underlying medical conditions, such as diabetes mellitus, renal impairment, cirrhosis, and malignancy are at greater risk. The presentations of melioidotic septic arthritis often mimic other disease processes and patients may not always be clinically septic. We present a case of septic arthritis due to B. pseudomallei in a 66-year-old male with diabetes mellitus presenting with a history of fever and ankle swelling. Follow-up ankle X-ray showed soft tissue swelling. Synovial fluid and blood samples grew B. pseudomallei. The patient improved gradually after parenteral administration of ceftazidime (2 g 8-hourly) and cotrimoxazole (1440 mg 8-hourly). He was discharged on oral cotrimoxazole (1440 mg 12-hourly), doxycycline (100 mg 12-hourly), and chloramphenicol (500 mg 6-hourly) for 6 months. This case highlights the possible occurrence of melioidotic septic arthritis, and the importance of prompt initiation of appropriate antimicrobials to achieve good outcomes.
Study site: Emergency department, University of Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
Deep surgical site infection is a devastating consequence of total joint arthroplasty. The use of antibiotic impregnated bone cement is a well-accepted adjunct for treatment of established infection and prevention of deep orthopaedic infection. It allows local delivery of the antibiotic at the cement-bone interface and sustained release of antibiotic provides adequate antibiotic coverage after the wound closure. Preclinical testing, randomised and clinical trials indicate that the use of antibiotic-impregnated bone cement is a potentially effective strategy in reducing the risk of deep surgical site infection following total joint arthroplasty. The purpose of this study was to assess antibacterial activity of erythromycin and colistin impregnated bone cement against strains of organisms' representative of orthopaedic infections including Gram-positive and Gram-negative aerobic organisms: Staphylococcus aureus, coagulase-negative Staphylococci, Enterococcus sp., Proteus sp., Klebsiella sp., Pseudomonas sp., and Escherichia coli. Pre-blended Simplex P bone cement with the addition of erythromycin and colistin (Howemedica Inc) was mixed thoroughly with 20ml liquid under sterile conditions to produce uniform cylindrical discs with a diameter of 14mm and thickness of 2mm. 24-48 hour agar cultures of Staphylococcus aureus, coagulase-negative Staphylococci, Enterococcus sp.,Proteus sp., Klebsiella sp.,Pseudomonas sp., and Escherichia coli were used for the agar diffusion tests. The agar plates were streaked for confluent growth followed by application of erythromycin and colistin impregnated bone cement disc to each agar plate. The plates were incubated at 30 degrees C and examined at 24, 48, 72 hours, and four and five days after the preparation of the impregnated cement. The susceptibility of Staphylococcus aureus to the control discs was most clearly demonstrated showing a distinct zone of inhibition. The zone observed around coagulase-negative Staphylococci, Klebsiella sp., Pseudomonas sp., and Escherichia coli were also significant. However, there was no zone of inhibition or signs of antibacterial activity at the cemented surface were detected around discs with Enterococcus sp. and Proteus sp. The results showed that Simplex P bone cement with the addition of erythromycin and colistin was effective against most of the broad spectrum organisms encountered during total joint arthroplasty. The activity of Simplex P bone cement impregnated with erythromycin and colistin is mainly during the first 72 hours.
Antibiotic-loaded bone cement has been used as prophylaxis against infection in total joint replacement surgery. Its effect on the mechanical strength of cement is a major concern as high dose of antibiotic was associated with a significant reduction in mechanical strength of bone cement. However, the cut-off antibiotic that weakens the mechanical strength of cement remains to be determined. This study was undertaken to observe the changes in the mechanical properties of bone cement with gradual increments of Cefuroxime antibiotic. Cefuroxime at different doses: 0, 1.5, 3.0 and 4.5gm were added to a packet of 40gm bone cement (Simplex P) and study samples were prepared by using third generation cementing technique. Mechanical impact, flexural and tensile strength were tested on each sample. Significant impact and tensile strength reduction were observed after addition of 4.5 gm of Cefuroxime. However, flexural strength was significantly reduced at a lower dose of 3.0 gm. The maximum dose of Cefuroxime to be safely added to 40mg Surgical Simplex P is 1.5gm when third generation cementing technique is used. Further study is needed to determine whether it is an effective dose as regards to microbiological parameters.
Staphylococcus aureus is an important human pathogen in both hospital and the community that has demonstrated resistance to all currently available antibiotics over the last two decades. Multidrug-resistant isolates of methicillin-resistant S. aureus (MRSA) exhibiting decreased susceptibilities to glycopeptides has also emerged, representing a crucial challenge for antimicrobial therapy and infection control. The availability of complete whole-genome nucleotide sequence data of various strains of S. aureus presents an opportunity to explore novel compounds and their targets to address the challenges presented by antimicrobial drug resistance in this organism. Study compounds α-amyrin [3β-hydroxy-urs-12-en-3-ol (AM)], betulinic acid [3β-hydroxy-20(29)-lupaene-28-oic acid (BA)] and betulinaldehyde [3β-hydroxy-20(29)-lupen-28-al (BE)] belong to pentacyclic triterpenoids and were reported to exhibit antimicrobial activities against bacteria and fungi, including S. aureus. The MIC values of these compounds against a reference strain of methicillin-resistant S. aureus (MRSA) (ATCC 43300) ranged from 64 µg/ml to 512 µg/ml. However, the response mechanisms of S. aureus to these compounds are still poorly understood. The transcription profile of reference strain of MRSA treated with sub-inhibitory concentrations of the three compounds was determined using Affymetrix GeneChips. The findings showed that these compounds regulate multiple desirable targets in cell division, two-component system, ABC transporters, fatty acid biosynthesis, peptidoglycan biosynthesis, aminoacyl-tRNA synthetase, ribosome and β-lactam resistance pathways which could be further explored in the development of therapeutic agents for the treatment of S. aureus infections.
The development of reliable and ecofriendly approaches for the production of nanomaterials is a significant aspect of nanotechnology nowadays. One of the most important methods, which shows enormous potential, is based on the green synthesis of nanoparticles using plant extract. In this paper, we aimed to develop a rapid, environmentally friendly process for the synthesis silver nanoparticles using aqueous extract of sumac. The bioactive compounds of sumac extract seem to play a role in the synthesis and capping of silver nanoparticles. Structural, morphological and optical properties of the nanoparticles were characterized using FTIR, XRD, FESEM and UV-Vis spectroscopy. The formation of Ag-NP was immediate within 10 min and confirmed with an absorbance band centered at 438 nm. The mean particle size for the green synthesized silver nanoparticles is 19.81 ± 3.67 nm and is fairly stable with a zeta potential value of -32.9 mV. The bio-formed Ag-NPs were effective against E. coli with a maximum inhibition zone of 14.3 ± 0.32 mm.
Red man syndrome (RMS) is the occurrence flushing, pruritus, chest pain, muscle spasm or hypotension during vancomycin infusion. It usually happens as a result of rapid infusion of the drug but may also occur after slow administration. The frequency and severity of this phenomenon diminish with repeated administration of vancomycin. A case is presented whereby RMS occurred while prophylactic antibiotic against infective endocarditis was administered.