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(A) Re-epithelialisation in patients treated with Polyspectran. In 14 days, about 75% of the corneal ulcers were healed. (B) The relation between ulcer size and time to healing. (C) Culture negative ulcers appear to have a shorter time to heal compared with ulcers with a positive culture. (D) There is no difference in time to healing at ulcers with positive or negative Gram stain.
Source publication
To evaluate the clinical efficacy and safety of topical polymyxin B, neomycin, and gramicidin for the treatment of suspected bacterial corneal ulceration at the Leiden University Medical Center.
Patients with a diagnosis of a suspected bacterial corneal ulcer between April 1995 and February 2002 were retrospectively identified and reviewed; clinica...
Contexts in source publication
Context 1
... the patients who completed treatment, corneal re- epithelialisation occurred in 68 of 69 ulcers (99%), and took on average 12.6 days (median 8 (IQR 4-14) days). Thus, within one week of treatment initiation, about half of the patients exhibited corneal epithelial closing (fig 2A). ...
Context 2
... single most important determinant of time to complete re-epithelialisation was the ulcer size on diagnosis (p,0.0001) ( fig 2B). The time to complete re-epithelialisation did not differ (p = 0.08) between patients with a positive or negative culture, though there was a trend towards Table 1 Characteristics of 91 patients with bacterial corneal ulceration ...
Context 3
... longer healing time in the former group ( fig 2C). The healing time of ulcers with Gram positive bacteria did not differ (p = 0.60) from that with Gram negative bacilli on smear ( fig 2D). ...
Citations
... A combination preparation eyedrop of polymyxin-B, neomycin, and gramicidin as well as moxifloxacin eye drops were started and administered by the nurse on an hourly alternating basis at day and night. In literature, the combination of polymyxin-B, neomycin and gramicidin [4] as well as moxifloxacin [5] have been described as highly effective for the treatment of bacterial corneal ulcers. With this therapy, we used commercially available antibiotic eye drops with good clinical effectiveness, a broad-spectrum antibacterial activity, and few side effects. ...
Background
This case report describes the course and therapeutic management of a fast-spreading bacterial keratitis caused by multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa).
Case presentation
A 27-year-old male contact lens wearer presented with a multi-resistant, fast spreading P. aeruginosa keratitis. After initial resistance to various antibiotic therapies, testing revealed a MDR P. aeruginosa. The keratitis was treated successfully with specially prepared 50 mg/ml off-label meropenem eye drops for 18 days as well as systemic meropenem for seven days with rapid improvement of the corneal infiltrate.
Conclusion
This case report demonstrates the combination of topical and systemic meropenem as a useful treatment option for corneal ulcers caused by MDR P. aeruginosa.
... The Topical chemotherapy has been successfully applied to ophthalmic infections (Bosscha et al., 2004). A combination of the antibiotics neomycin, polymyxin B, and gramicidin (Neo-Poly gramicidin) had broad spectrum antibacterial activity (Gibson, 1983). ...
... The Topical chemotherapy has been successfully applied to ophthalmic infections (Bosscha et al., 2004). A combination of the antibiotics neomycin, polymyxin B, and gramicidin (Neo-Poly gramicidin) had broad spectrum antibacterial activity (Gibson, 1983). ...
The objective of this study was to study the synergistic antitumor effect of lipophilic bismuth nanoparticles (BisBAL NPs) with the antibiotic solution Neo-Poly gramicidin on human cervical tumor cells. The effect of BisBAL NPs and Neo-Poly gramicidin solution on cervical cancer cell line (HeLa) was determined by the MTT cell viability assay and fluorescence microscopy. After a 24-h exposure to 0.1× Neo-Poly gramicidin HeLa cell growth decreased 94%. Fluorescence microscopy confirmed the antitumor effect cell death was higher among treated than among non-treated cells cells. Individually, gramicidin (0.04 mg/mL) inhibited HeLa tumor cell growth most (40%), and neomycin (0.04 mg/mL) least (21%). Gramicidin (0.3 mg/mL) in combination with different concentrations (1–150 μM) of BisBAL NPs had a synergistic antitumor effect against HeLa cells, reaching an < 86% tumor growth inhibition. As far as we know, we are the first to describe the antitumor activity of the antibiotic Neo-Poly gramicidin on a human cervical cancer cell line. The action mechanism of gramicidin/BisBAL NP is based on a strong damage on cell membrane and nucleus of tumor cells. A synergistic effect of gramicidin with BisBAL NPs may be useful as an alternative therapy for cervical cancer patients.
... The authors of this study suggested that the lack of statistically significant differences between the placebo and peptide-treated group could be due to the small sample size of 14 patients in each group (Hirunwiwatkul and Wachirasereechai, 2005). In another clinical study using a larger sample size of 91 patients, the effect of this ophthalmic solution on the duration of cure of bacterial-positive corneal ulcers was reported (Bosscha et al., 2004). An average of 12.5 days was required for complete re-epithelialization of these ulcers. ...
Antimicrobial peptides (AMPs) or host defense peptides protect the host against various pathogens such as yeast, fungi, viruses and bacteria. AMPs also display immunomodulatory properties ranging from the modulation of inflammatory responses to the promotion of wound healing. More interestingly, AMPs cause cell disruption through non-specific interactions with the membrane surface of pathogens. This is most likely responsible for the low or limited emergence of bacterial resistance against many AMPs. Despite the increasing number of antibiotic-resistant bacteria and the potency of novel AMPs to combat such pathogens, only a few AMPs are in clinical use. Therefore, the current review describes (i) the potential of AMPs as alternatives to antibiotics, (ii) the challenges toward clinical implementation of AMPs and (iii) strategies to improve the success rate of AMPs in clinical trials, emphasizing the lessons we could learn from these trials.
... [36], and to the limited ocular penetration of antifungals [37]. Notably, PMB can be formulated for ophthalmic use [16], which is described as a highly effective drug on bacterial corneal ulcerations [38]. Moreover, the use of such antimicrobial agent constitutes a potential alternative treatment that may improve the outcome in some critical infections caused by MDR fungi, such as the recent MDR Fusarium keratitis-case report in a 46-year-old man who was still declining even the maximal therapeutic support and therapeutic keratoplasty [36]. ...
Background
Although antifungals are available and usually used against fungal infections, multidrug-resistant (MDR) fungal pathogens are a growing problem for public health. Moreover, fungal infections have become more prevalent nowadays due to the increasing number of people living with immunodeficiency. Thus, previously rarely-isolated and/or unidentified fungal species including MDR yeast and moulds have emerged around the world. Recent works indicate that polymyxin antibiotics (polymyxin B and colistin) have potential antifungal proprieties. Therefore, investigating the in vitro activity of these molecules against clinical multidrug-resistant yeast and moulds could be very useful.
Methods
In this study, a total of 11 MDR yeast and filamentous fungal strains commonly reported in clinical settings were tested against polymyxin antibiotics. These include strains belonging to the Candida, Cryptococcus and Rhodotorula yeast genera, along with others belonging to the Aspergillus, Fusarium, Scedosporium, Lichtheimia and Rhizopus mould genera. The fungicidal or fungistatic action of colistin against clinical yeast strains was determined by the time-kill study. Further, a checkerboard assay for its combination with antifungal agents, usually used in clinical practices (amphotericin B, itraconazole, voriconazole), was carried out against multi-drug resistant fungal strains.
Results
Polymyxin B and colistin exhibited an antifungal activity against all MDR fungal strains tested with MICs ranging from 16 to 128 μg/ml, except for the Aspergillus species. In addition, colistin has a fungicidal action against yeast species, with minimum fungicidal concentrations ranging from 2 to 4 times MICs. It induces damage to the MDR Candida albicans membrane. A synergistic activity of colistin-amphotericin B and colistin-itraconazole associations against Candida albicans and Lichtheimia corymbifera strains, respectively, and colistin-fluconazole association against Rhodotorula mucilaginosa, was demonstrated using a checkerboard microdilution assay.
Conclusion
colistin could be proposed, in clinical practice, in association with other antifungals, to treat life-threatening fungal infections caused by MDR yeasts or moulds.
... This material is used in pharmaceutical forms for isolated topical use, or in combination with other antibiotics for the treatment of bacterial infections (Bosscha et al., 2004;Zaias et al., 1981). ...
Gramicidin, an antimicrobial peptide active against Gram positive bacteria, is commonly used in pharmaceutical preparations for topical use. Considering that only the turbidimetric method has been described in the literature, the present study sought to develop and validate an agar diffusion method for the dosage of gramicidin. The method was developed and validated using the Kocuria rhizophila ATCC 9341 as a test microorganism. Two designs were used: a 3×3 parallel-line model, and a 5×1 standard curve. The validation demonstrated that the method follows the linear model (r 2= 0.994), presenting a significant regression between the zone diameter of growth inhibition and the logarithm of the concentration within the range of 5 to 25.3 μg/mL. The results obtained for both designs were precise, having a relative standard deviation (R.S.D.) for intra-day precision of 0.81 for the 3×3 assay and 1.90 for the 5×I assay. For the inter-day precision, the R.S.D. was 1.35 for the 3x3 and 2.64 for the 5×1. The accuracy was verified and results confirmed to be accurate, having a tolerance interval of 95%, which lay within permitted limits and appropriate trueness. In addition, the method was considered selective, with limit of detection and upper and lower limits of quantification of 2.00, 5.00 and 25.3 tg/mL, respectively. No difference in precision between the designs used in the agar diffusion method was evident (p>0.05). The method proved to be appropriate for the microbiological dosage of the raw material gramicidin.
... No serious adverse events were reported, although 8% of patients reported toxic punctate epitheliopathy or allergic reactions. 30 Similarly, combination trimethoprim and polymyxin B was well tolerated in a bacterial conjunctivitis study, with a 7% rate of adverse effects noted. 31 ...
Bacterial conjunctivitis is a common ocular infection that is generally treated empirically with a broad-spectrum antibiotic. The more common pathogens causing bacterial conjunctivitis include Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus epidermidis, and Moraxella species. Several antibiotics traditionally used to treat bacterial conjunctivitis are no longer widely prescribed because of increased bacterial resistance and/or safety concerns. The introduction of the fluoroquinolone class of anti-infectives offered effective and better tolerated treatment options. Nonetheless, successful therapy for bacterial conjunctivitis continues to be limited by several factors. A primary concern is the development of bacterial resistance that may be impacted not only by widespread antibiotic use but also by antibacterial pharmacokinetics, such as maintenance of insufficient bactericidal concentrations at the site of infection. In addition, poor adherence to prescribed regimens that require frequent administration, along with undesirable adverse events, affects the development of bacterial resistance and the success of treatment regimens. This article reviews current antibacterial agents used to treat bacterial conjunctivitis, factors that limit their successful use in treatment, and options for future development of more effective topical ophthalmic anti-infective agents.
... In terms of clinical use, polymyxin B has many similarities with colistimethate sodium and colistin sulfate. Specifically, polymyxin B and colistin sulfate have both been used widely for the treatment of otic, ophthalmic and skin infections [49][50][51][52][53]. In addition, intravenous polymyxin B and colistimethate sodium have also been used for the treatment of critically ill patients with nosocomial infections caused by multidrug-resistant or polymyxin-only-sensitive Gram-negative bacteria [44,[54][55][56][57][58]. ...
Hospital-acquired infections due to multidrug-resistant gram-negative bacteria constitute major health problems, since the medical community is continuously running out of available effective antibiotics and no new agents are in the pipeline. Polymyxins, a group of antibacterials that were discovered during the late 1940s, represent some of the last treatment options for these infections. Only two polymyxins are available commercially, polymyxin E (colistin) and polymyxin B. Although several reviews have been published recently regarding colistin, no review has focused on the similarities and differences between polymyxin B and colistin. These two medications have many similarities with respect to mechanism of action, antimicrobial spectrum, clinical uses and toxicity. However, they also differ in several aspects, including chemical structure, formulation, potency, dosage and pharmacokinetic properties.
Bacterial infection caused by multidrug-resistant Pseudomonas aeruginosa has become a challenge in clinical practice. Polymyxins are used as the last resort agent for otherwise untreatable Gram-negative bacteria, including multidrug-resistant P.aeruginosa. However, pharmacodynamic (PD) and pharmacokinetic (PK) data on polymyxins suggest that polymyxin monotherapy is unlikely to generate reliably efficacious plasma concentrations. Also, polymyxin resistance has been frequently reported, especially among multidrug-resistant P.aeruginosa, which further limits its clinical use. A strategy for improving the antibacterial activity of polymyxins and preventing the development of polymyxin resistance is to use polymyxins in combination with other agents. In this study, we have demonstrated that resveratrol, a well tolerated compound, has synergistic effects when tested in vitro with polymyxin B on antibacterial and anti-biofilm activities. However, its’ systemic use is limited as the required high plasma levels of resveratrol are not achievable. This suggests that it could be a partner for the combination therapy of polymyxin B in the treatment of topical bacterial infection caused by MDR P.aeruginosa.
Infectious diseases have for centuries ranked with wars and famine as major challenges to human progress and survival. They remain among the leading causes of death and disability worldwide. Against a constant background of established infections, epidemics of new and old infectious diseases periodically emerge, greatly magnifying the global burden of infections. According to the World Health Organization (WHO), about 15 million (>25%) of 57 million annual deaths worldwide are estimated to be related directly to infectious diseases. While “single-target drugs” (STDs) failed to provide optimal treatment of infectious diseases, polypharmacology is rising above the horizon for better cure. This chapter provides a brief introduction to the three main types of polypharmacology approaches (combination drug therapy [CDT], fixed-dose combination [FDC] and multitarget drug [MTD]) and their current status of application in the clinical setting as well as their potential to the discovery and development of new drugs for infectious diseases therapy.KeywordsAnti-infection polypharmacologyBacterial infectionViral infectionChagas diseaseMultitarget therapy
