Nonantimicrobial Agents Research Articles

Verapamil increases susceptibility of colistin-resistant Acinetobacter baumannii to colistin

Acinetobacter baumannii, which is predominantly responsible for hospital-acquired infections, presents a tremendous clinical challenge due to its increasing antibiotic resistance to colistin (COL), a last-line antibiotic. As a result, the combination of antimicrobial and non-antimicrobial agents is emerging as a more popular treatment approach against infections caused by COL-resistant A. baumannii. This study administered COL and verapamil (VER), that is an antihypertensive and antiarrhythmic agent. We found that the susceptibility of A. baumannii to COL was restored both in vitro and in vivo. Scanning electron microscope and Crystal violet staining showed inhibition of the VER/COL combination on bacterial biofilm formation. Cytotoxicity assay and haemolysis test were used to confirm in vitro safety evaluation. Further experiments using propidium iodide staining revealed that the VER/COL combination improved the therapeutic efficacy of COL by modifying the permeability of bacterial membranes. As demonstrated by reactive oxygen species experiments, the drug combination caused the accumulation of bacterial reactive oxygen species and their eventual death. Additionally, VER/COL treatment significantly reduced the efflux of Rhodamine 123 (Rh123). For the first time, this study identifies the anti-hypertensive drug VER as a COL potentiator against A. baumannii, providing a potential treatment approach against A. baumannii infections and improving patient outcomes.

Exploring non-antimicrobial agents as antibiotic alternatives: an in vitrostudy

Background:Microorganisms cause periapical and pulpal disorders, making root canal treatment (RCT) essential. Due to complex canal anatomy, bacteria may persist despite cleaning. Intracanal medicaments, such as calcium hydroxide and chlorhexidine, help eliminate residual bacteria, reduce inflammation, and enhance treatment outcomes by improving disinfection and compatibility.Aim:To assess the antimicrobial effectiveness of Triple Antibiotic Paste (TAP), Modified TAP, Sertraline (SSRI), Atorvastatin and the combination of Atorvastatin and Sertraline against Enterococcus faecalis.Materials and methods:A total of 30 samples were made, with 6samples from each group: TAP, Sertraline, Atorvastatin, Modified TAP, and Sertraline + Atorvastatin. The antimicrobial efficacy of the medicaments was evaluated using an agar well diffusion test by measuring inhibition zones around the medicaments. Statistical analysis included one-way ANOVA, with significance set at p < 0.05.Results:A significant difference (p=0.001) in the diameter of growth inhibition zones was observed. The maximum inhibitory zone was found in Group 5: Sertraline+Atorvastatin.Conclusion:The combination of sertraline and atorvastatin demonstrated superior antimicrobial efficacy compared to modified TAP, TAP, sertraline, and atorvastatin used alone.

Mechanisms of emerging resistance associated with non-antibiotic antimicrobial agents: a state-of-the-art review.

Although the development of resistance by microorganisms to antimicrobial drugs has been recognized as a global public health concern, the contribution of various non-antibiotic antimicrobial agents to the development of antimicrobial resistance (AMR) remains largely neglected. The present review discusses various chemical substances and factors other than typical antibiotics, such as preservatives, disinfectants, biocides, heavy metals and improper chemical sterilization that contribute to the development of AMR. Furthermore, it encompasses the mechanisms like co-resistance and co-selection, horizontal gene transfer, changes in the composition and permeability of cell membrane, efflux pumps, transposons, biofilm formation and enzymatic degradation of antimicrobial chemicals which underlie the development of resistance to various non-antibiotic antimicrobial agents. In addition, the review addresses the resistance-associated changes that develops in microorganisms due to these agents, which ultimately contribute to the development of resistance to antibiotics. In order to prevent the indiscriminate use of chemical substances and create novel therapeutic agents to halt resistance development, a more holistic scientific approach might provide diversified views on crucial factors contributing to the persistence and spread of AMR. The review illustrates the common and less explored mechanisms contributing directly or indirectly to the development of AMR by non-antimicrobial agents that are commonly used.

Development of Anti-Acne Topical Gel Formulation Containing Herbal Extract

Systemic and topical antimicrobials are effective in the treatment of inflammatory acne vulgaris; however, widespread use of these agents is becoming increasingly associated with the emergence of resistant pathogens raising concerns about microorganism resistance and highlighting the need for alternative non-antimicrobial agents for the treatment of acne. Several multinational companies like Lakme Cosmetics Ltd., Lotus Ltd., Ayur Healthcare Ltd., Patanjali Ayurveda, etc. have started developing anti-acne products which contain multiple extracts of common Indian plants. The study aims to develop herbal gel formulations containing Bougainvillea glabra extract (aqueous, methanol, ethyl acetate, and petroleum ether) for the treatment of acne. The formulations were comprehensively evaluated for Physical evaluation, Washability, Skin irritation test, Spreadability, pH, Viscosity, Extrudability, Swelling index, and Accelerated stability studies as per the standard methods. Amongst all the formulations studied, batch F2 was found optimum for all the parameters. The extraction yield was found to be 11.21%. Bougainvillea glabra aqueous extract showed low anti-bacterial activity whereas both Bougainvillea glabra methanol extract and Bougainvillea glabra ethyl acetate extract expressed moderate anti-bacterial activity with average MIC value against E. coli and B. subtilis. In contrast to them, the petroleum ether extract of Bougainvillea glabra presented highest anti-bacterial activity, however, the activity was less pronounced than the standard drug Clindamycin. The formulations (F1-F4) represented alike results with that of the extracts and expressed lesser activity as compared to the marketed herbal product.

Antimicrobial Treatment of Pseudomonas aeruginosa Severe Sepsis.

Pseudomonas aeruginosa is a pathogen often encountered in a healthcare setting. It has consistently ranked among the most frequent pathogens seen in nosocomial infections, particularly bloodstream and respiratory tract infections. Aside from having intrinsic resistance to many antibiotics, it rapidly acquires resistance to novel agents. Given the high mortality of pseudomonal infections generally, and pseudomonal sepsis particularly, and with the rise of resistant strains, treatment can be very challenging for the clinician. In this paper, we will review the latest evidence for the optimal treatment of P. aeruginosa sepsis caused by susceptible as well as multidrug-resistant strains including the difficult to treat pathogens. We will also discuss the mode of drug infusion, indications for combination therapy, along with the proper dosing and duration of treatment for various conditions with a brief discussion of the use of non-antimicrobial agents.

Bacterial community structure and bacterial isolates having antimicrobial potential in shrimp pond aquaculture

Diseases outbreaks in pond aquaculture have resulted in huge losses to the aquaculture industry. The emergence of non-antimicrobial and environment friendly agents (probiotics) is the potential consideration for the healthy shrimp aquaculture. The present study was aimed to compare the bacterial community compositions in shrimp ponds and surrounding seawater, as well as isolate probiotic bacteria from the shrimp ponds. Based on the high-throughput of 16S rRNA gene sequencing, all sequences were assigned to 3584 unique operational taxonomic units (OTUs) at 97% similarity levels, which were affiliated with 24 phyla, 54 classes, 235 families, and 367 genera. The 10 most abundant phyla were Bacteroidota, Proteobacteria, Actinobacteriota, Planctomycetota, Cyanobacteria, Chloroflexi, Firmicutes, Desulfobacterota, Patescibacteria and Verrucomicrobiota. Notably, the alpha diversity (Shannon diversity) of shrimp ponds was significantly differences (P < 0.05) with that of surrounding seawater. There were 2498 and 791 unique OTUs in shrimp ponds and surrounding seawater, respectively. A total of 15 isolates were obtained in the culturable bacterial diversity, and the antibacterial activities were recorded for potential probiotic bacterial isolates against different tested bacterial isolates including pathogenic bacteria. An isolate Hallobacillusmarinus HMALI004 showed strong inhibitory effects against three pathogenic bacteria, Vibrio cholerae CECT 514, non AHPND V. parahaemolyticus BCRC12959 and AHPND V. parahaemolyticus PD-2. The isolates Algophigussanaruensis AGALI005, Algoriphagus taiwanensis ATALI009 and Bacillusaequororis BAALI008 were also identified as potential probiotics strains.

Propranolol, chlorpromazine and diclofenac restore susceptibility of extensively drug-resistant (XDR)-Acinetobacter baumannii to fluoroquinolones.

Nosocomial infections caused by extensively drug-resistant (XDR) or Pan-Drug resistant (PDR) Acinetobacter (A.) baumannii have recently increased dramatically creating a medical challenge as therapeutic options became very limited. The aim of our study was to investigate the antibiotic-resistance profiles and evaluate the various combinations of ciprofloxacin (CIP) or levofloxacin (LEV) with antimicrobial agents and non-antimicrobial agents to combat antimicrobial resistance of XDR A. baumannii. A total of 100 (6.25%) A. baumannii clinical isolates were recovered from 1600 clinical specimens collected from hospitalized patients of two major university hospitals in Upper Egypt. Antimicrobial susceptibility tests were carried out according to CLSI guidelines. Antimicrobial susceptibility testing of the respective isolates showed a high percentage of bacterial resistance to 19 antimicrobial agents ranging from 76 to99%. However, a lower percentage of resistance was observed for only colistin (5%) and doxycycline (57%). The isolates were categorized as PDR (2; 2%), XDR (68; 68%), and multi-drug resistant (MDR) (30; 30%). Genotypic analysis using ERIC-PCR on 2 PDR and 32 selected XDR isolates showed that they were not clonal. Combinations of CIP or LEV with antibiotics (including, ampicillin, ceftriaxone, amikacin, or doxycycline) were tested on these A. baumannii non-clonal isolates using standard protocols where fractional inhibitory concentrations (-FICs) were calculated. Results of the respective combinations showed synergism in 23.5%, 17.65%, 32.35%, 17.65% and 26.47%, 8.28%, 14.71%, 26.47%, of the tested isolates, respectively. CIP or LEV combinations with either chlorpromazine (CPZ) 200 μg/ml, propranolol (PR) in two concentrations, 0.5 mg/ml and 1.0 mg/ml or diclofenac (DIC) 4 mg/ml were carried out and the MIC decrease factor (MDF) of each isolate was calculated and results showed synergism in 44%, 50%, 100%, 100% and 94%, 85%, 100%, 100%, of the tested isolates, respectively. In conclusion, combinations of CIP or LEV with CPZ, PR, or DIC showed synergism in most of the selected PDR and XDR A. baumannii clinical isolates. However, these combinations have to be re-evaluated in vivo using appropriate animal models infected by XDR- or PDR- A. baumannii.

Topical treatment for facial burns.

Background Burn injuries are an important health problem. They occur frequently in the head and neck region - the area central to a person's identity, that provides our most expressive means of communication. Topical interventions are currently the cornerstone of treatment of partial-thickness burns to the face. Objectives To assess the effects of topical interventions on wound healing in people with facial burns of any depth. Search methods We searched the Cochrane Wounds Group Specialised Register (searched 12 November 2012); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 10); Ovid MEDLINE (1950 to November Week 1 2012); Ovid MEDLINE - In-process & Other Non-Indexed Citations (searched November 12, 2012); Ovid EMBASE (1980 to 2012 Week 45); and EBSCO CINAHL (1982 to 9 November 2012) for relevant trials. We did not apply date or language restrictions. Selection criteria Randomised controlled trials (RCTs) that evaluated the effects of topical treatment for facial burns were eligible for inclusion in this review. Data collection and analysis Two review authors independently assessed and included the references identified by the search strategy. Included trials were assessed using a risk of bias form, and data were extracted using a standardised data extraction sheet. For dichotomous and continuous outcomes, we calculated risk ratios and mean differences, respectively, both with 95% confidence intervals (CI). Main results We included five RCTs, comprising a total of 119 participants. Two studies compared two different antimicrobial agents and three compared a biological or bioengineered skin substitute with an antimicrobial agent. All studies had small sample sizes and were at high risk of bias. Heterogeneity of interventions and outcomes prevented pooling of data. In three studies time to complete wound healing was significantly shorter for those using a skin substitute than for those using an antibacterial agent, but the quality of the evidence was low. Pain was significantly reduced with the use of skin substitutes in both studies that reported this outcome in all groups, range mean differences -2.00 (95% CI -3.82 to -0.18) to -4.00 (95% CI -5.05 to -2.95) on a 10-point scale. Authors' conclusions There is insufficient high quality research and evidence to enable conclusions to be drawn about the effects of topical interventions on wound healing in people with facial burns.

Microbial Resistance in Urinary Tract Infections.

ObjectiveTo determine the pattern of microbes responsible for urinary tract infections and their susceptibility to antimicrobial agents.MethodsThis was a prospective, observational study conducted at Benazir Bhutto Hospital, Rawalpindi, Pakistan. The urine samples of 440 patients were collected and sent for culture and sensitivity analysis. The results were recorded on a proforma. The data were analyzed using IBM Statistical Package for Social Sciences (SPSS) version 22 (IBM Corp., Armonk, NY). Descriptive statistics were used to describe the data. Chi-square test was applied to determine the significance of the difference between gender and microorganisms as well as microorganism and antimicrobial sensitivity. P-value of less than 0.05 was considered significant.ResultsOut of 440 urine samples, 144 culture-positive samples had been obtained from male participants and 296 culture-positive samples had been obtained from female participants. The most common organism on analysis was Escherichia coli. There were more rates of resistance in males. The organisms were most susceptible to fosfomycin and imipenem (p = 0.01). The organisms were resistant to ceftazidime (p = 0.01).ConclusionIn Pakistan, most patients with resistance present with mild symptoms instead of severe clinical manifestations. Therefore, there is a need to reduce the over-prescription of antibiotics for urinary tract infections, especially in cases when other non-antimicrobial agents can be used.

Phenotypic zinc resistance does not correlate with antimicrobial multi-resistance in fecal E. coli isolates of piglets

BackgroundFollowing the ban on antimicrobial usage for growth promotion in animal husbandry in the EU, non-antimicrobial agents including heavy metal ions (e.g. zinc and copper), prebiotics or probiotics have been suggested as alternatives. Zinc has extensively been used in pig farming, particularly during weaning of piglets to improve animal health and growth rates. Recent studies, however, have suggested that high dietary zinc feeding during weaning of piglets increases the proportion of multi-drug resistant E. coli in the gut, contraindicating the appropriateness of zinc as an alternative. The underlying mechanisms of zinc effects on resistant bacteria remains unclear, but co-selection processes could be involved. In this study, we determined whether E. coli isolates from intestinal contents of piglets that had been supplemented with high concentrations of zinc acquired a higher tolerance towards zinc, and whether multi-drug resistant isolates tolerated higher zinc concentrations. In addition, we compared phenotypic zinc and copper resistance of E. coli isolates for possible correlation between phenotypic resistance/tolerance to different bivalent ionic metals.ResultsWe screened phenotypic zinc/copper tolerance of 210 isolates (including antimicrobial resistant, multi-drug resistant, and non-resistant E. coli) selected from two, independent zinc-feeding animal trials by determining a zinc/copper minimal inhibitory concentration (Merlin, Bornheim-Hersel, Germany). In both trials, groups of piglets were supplemented either with high dietary zinc (> 2000 ppm) or control (50–70 ppm, background) concentrations. Our observations showed that high concentration zinc exposure did not have an effect on either zinc or copper phenotypic tolerance of E. coli isolates from the animals. No significant association was found between antimicrobial resistance and phenotypic zinc/copper tolerance of the same isolates.ConclusionOur findings argue against a co-selection mechanism of antimicrobial drug-resistance and zinc tolerance after dietary zinc supplementation in weaning piglets. An explanation for an increase in multi-drug resistant isolates from piglets with high zinc dietary feeding could be that resistant bacteria to antimicrobial agents are more persistent to stresses such as zinc or copper exposure.

In vitro interactions of ambroxol hydrochloride or amlodipine in combination with antibacterial agents against carbapenem-resistant Acinetobacter baumannii.

The aim of this study was to investigate the in vitro interactions of ambroxol hydrochloride (ABH) or amlodipine (AML) with commonly used antibacterial agents, including meropenem, imipenem-cilastatin sodium, biapenem, cefoperazone-sulbactam, polymyxin B, and tigecycline, against six carbapenem-resistant Acinetobacter baumannii (CRAB) clinical isolates. Drug interactions were interpreted using two models, that is, the fractional inhibitory concentration index (FICI) model and the percentage of growth difference (ΔE) model. The results show that a majority of the combination groups exhibited partial synergy and additive interactions, such as the combinations of carbapenems and cefoperazone-sulbactam (SCF) with ABH or AML. While the combination of PB/AML exhibited synergistic interactions against all tested isolates, and PB/ABH exhibited synergistic interactions against two isolates. The FICI and ΔE model correlated very well for the combinations of PBABH and PB/AML against AB2. The combinations of TGC with ABH or AML mainly exhibited additive and indifferent interactions. There were no antagonistic interactions observed in any of the combinations. In conclusion, this study revealed that the non-antibacterial agents ABH or AML can work synergistically or partial synergistically with antibacterial agents against CRAB. This finding is crucial for overcoming the carbapenem resistance of A. baumannii. SIGNIFICANCE AND IMPACT OF THE STUDY: Drug combination is an effective approach for the treatment of resistant bacterial infection. The significance of using drug combination is that it can reduce drug dosage requirements, reduce the toxic effects of agents and prevent or delay the emergence of drug resistance. This study measured the in vitro interactions between non-antimicrobial agents and antibacterial agents against carbapenem-resistant Acinetobacter baumannii and the results of this study provide new insight to find strategies to overcome the carbapenem resistance in A. baumannii.

Біоплівки. Сучасний стан і перспективи антимікробної терапії

Огляд присвячений аналізу сучасних даних щодо механізмів стійкості біоплівок до антимікробних засобів та пошуку нових активних речовин з антибіоплівковою активністю. Проведений аналіз літературних джерел показав, що біоплівка є гетерогенною багатоклітинною структурою, стійкість якої до впливу зовнішніх факторів (у т. ч. антимікробних речовин) визначається будовою позаклітинного матриксу, наявністю сигнальної системи (Quorum sensing), а також здатністю до переходу в метаболічно неактивний стан. Для підвищення ефективності антибіоплівкової терапії як перспективні розглядають речовини, які: 1) руйнують позаклітинний матрикс або підвищують його проникність; 2) впливають на систему Quorum sensing і синтез автоіндукторів; 3) впливають на метаболічно неактивні клітини або викликають їхню реверсію до активного стану. З метою подолання стійкості біоплівок окрім пошуку таргетних молекул також розглядають можливість застосування не антимікробних препаратів, створення молекул, подібних до білків людини та мікроорганізмів, а також застосування вірусів бактерій – бактеріофагів. Цей огляд може бути підґрунтям для дослідників, які прагнуть вивчати антибіоплівкові властивості нових речовин і розробляти потенційні лікарські засоби.

Sulfonamide Allergies.

As one of the earliest developed antimicrobial classes, sulfonamides remain important therapeutic options for the empiric and definitive treatment of various infectious diseases. In the general population, approximately 3–8% of patients are reported to experience a sulfonamide allergy. Sulfonamide allergies can result in various physical manifestations; however, rash is reported as the most frequently observed. In patients with human immunodeficiency virus (HIV), dermatologic reactions to sulfonamide antimicrobial agents occur 10 to 20 times more frequently compared to immunocompetent patients. This article describes the incidence, manifestations, and risk factors associated with sulfonamide allergies. The potential for cross-reactivity of allergies to sulfonamide antimicrobials with nonantimicrobial sulfonamide medications is also reviewed. Data suggest that substitutions at the N1 and N4 positions are the primary determinants of drug allergy instead of the common sulfonamide moiety. For patients with an indication for a sulfonamide antimicrobial with a listed allergy, it is important for healthcare practitioners to adequately assess the allergic reaction to determine appropriate management. Rechallenge and desensitization strategies may be appropriate for patients with delayed maculopapular eruptions, while alternative treatment options may be prudent for more severe reactions. Available data suggests a low risk of cross-allergenicity between sulfonamide antimicrobial and nonantimicrobial agents.

Medication-related anaphylaxis treated in hospital: Agents implicated, patient outcomes, and management lessons.

On background of increasing medication-related anaphylaxis rates in Australia, our aim was to determine epidemiology, outcomes, adverse drug reaction (ADR) reporting rates, and accuracy of coding in patients treated for nonantimicrobial medication-related anaphylaxis in our hospital network. From January 2010 to December 2015 patients treated in our hospital network for medication-related anaphylaxis were identified using International Classification of Diseases, 10th Edition diagnosis code T88.6. Cases were also extracted from the hospital ADR database. Medical records were reviewed to ensure consistent diagnosis and to extract clinical, documentation, and outcome data. Of 1110 patients coded as T88.6, 177 (15.9%) met the medication-related anaphylaxis definition. Eighty (40.8%) had anaphylaxis due to nonantimicrobial agents. Thirteen of these (16.3%) had a previous reaction to the same medication/group. In 51 (63.8%) patients, anaphylaxis occurred during inpatient stay, with 31 reactions occurring during surgery. Eighty-five medications were implicated, most commonly neuromuscular blocking agents (31, 36.5%) and nonsteroidal anti-inflammatory drugs. No trends were noted over the 6-year period, and there was no anaphylaxis-related mortality. Fifty-three (66.3%) patients were assessed in allergy clinics. One in 10 cases did not have the reaction documented in the discharge summary. Adverse drug reaction reports were received for 38 patients (47.5%). Although acute patient outcomes were excellent, gaps in practice were noted regarding ADR coding accuracy and reporting rates. One in 6 patients had a prior hypersensitivity reaction to a similar medication, so we recommend accurate documentation, ADR review with allergy follow-up, and patient held information to decrease re-exposure risk.

“Future” Threat of Gram-negative Resistance in Singapore

The emergence of multidrug-resistant gram-negative bacteria is challenging the treatment of serious nosocomial infections. This is an international trend that is mirrored in Singapore too. Reports of strains resistant to all currently available agents have surfaced here and possibly have taken root here as well. The direst situation is among the non-fermenters, Pseudomonas aeruginosa and Acinetobacter baumannii. This is followed closely by the Enterobacteriaceae family with their array of extended-spectrum beta-lactamases, AmpC beta-lactamases and carbapenemases. There are also resistance mechanisms such as efflux pumps and porins downregulation that effect resistance against multiple classes of agents. Potentiating these developments is the dwindling "pipeline" of new agents. Hence, there is a real concern that we are running out of options for our patients. Novel antibiotic combinations, enhanced infection control, antibiotic cycling, computer-assisted programmes, and maybe in the distant future, non-antimicrobial agents is all that we have.

RamA Confers Multidrug Resistance in Salmonella enterica via Increased Expression of acrB , Which Is Inhibited by Chlorpromazine

Salmonella enterica serovar Typhimurium SL1344, in which efflux pump genes (acrB, acrD, acrF, tolC) or regulatory genes thereof (marA, soxS, ramA) were inactivated, was grown in the presence of 240 antimicrobial and nonantimicrobial agents in the Biolog Phenotype MicroArray. Mutants lacking tolC, acrB, and ramA grew significantly worse than other mutants in the presence of 48 agents (some of which have not previously been identified as substrates of AcrAB-TolC) and particularly poorly in the presence of phenothiazines, which are human antipsychotics. MIC testing revealed that the phenothiazine chlorpromazine had antimicrobial activity and synergized with common antibiotics against different Salmonella serovars and SL1344. Chlorpromazine increased the intracellular accumulation of ethidium bromide, which was ablated in mutants lacking acrB, suggesting an interaction with AcrB. High-level but not low-level overexpression of ramA increased the expression of acrB; conferred resistance to chloramphenicol, tetracycline, nalidixic acid, and triclosan and organic solvent tolerance; and increased the amount of ethidium bromide accumulated. Chlorpromazine induced the modest overproduction of ramA but repressed acrB. These data suggest that phenothiazines are not efflux pump inhibitors but influence gene expression, including that of acrB, which confers the synergy with antimicrobials observed.

Nonantimicrobial Agents in the Prevention and Treatment of Traveler' Diarrhea

Among the nonantimicrobial agents that are available and useful for the prevention of traveler's diarrhea are bismuth subsalicylate-containing preparations, which can provide a rate of protection of up to 65% when taken 4 times daily. In one study, the probiotic Lactobacillus GG was found to provide 49% protection against traveler's diarrhea, but results with this agent and other probiotics have been highly variable and geographically inconsistent. Tannin albuminate plus ethacridine lactate provided 36% protection, but it is not widely available. Among the nonantimicrobial agents that are available and useful for the treatment of traveler's diarrhea are bismuth subsalicylate-containing preparations, which reduce the passage of loose stools by 16%-18%. The antisecretory and antimotility agent loperamide reduces the passage of loose stools by approximately 50% and has been especially useful, in combination with antimicrobial agents, in reducing the total duration of posttreatment diarrhea to a matter of hours.

Patients with sulfonamide antimicrobial “allergy”: Are they able to tolerate sulfonamide-containing non-antimicrobial agents?

Rationale The clinical significance of potential cross-reactivity between sulfonamide antimicrobials and other sulfonamide-containing medications is uncertain. Pharmacy records were surveyed to determine whether patients with a history of sulfonamide antimicrobial adverse reactions were prescribed other sulfonamide-containing non-antimicrobials and, if so, whether these patients experienced adverse reactions to those agents. Methods All inpatients and outpatients at Parkland Memorial Hospital with reported sulfonamide “allergy” were retrospectively cross-referenced with an extensive list of potentially cross-reactive drugs dispensed by the pharmacy over the past 8 years. Pharmacy records of adverse reactions to these non-antimicrobial sulfonamides were also surveyed. Results This search generated 247 drug dispensations in 215 patients, of whom 25 (11.6%) received medications from more than 1 class. Despite reporting a sulfonamide antimicrobial adverse reaction, each patient received 1 to 3 of the following sulfonamides: a sulfonylurea, thiazide, loop diuretic, carbonic anhydrase inhibitor, triptan, celecoxib, amprenavir, or dapsone (a sulfone). Four adverse reactions were listed (1.6% of drug dispensations), one each to glyburide, sumatriptan, furosemide, and celecoxib; none were serious or life-threatening. While a system establishing absence of cross-reactions in patients was not available, 80% of drugs were refilled at least once, suggesting they were tolerated. Conclusions In general, patients who report a sulfonamide “allergy” can safely receive a wide variety of potentially cross-reactive non-antimicrobial sulfonamides, as suggested by repeated dispensations in most, lack of serious reported adverse reactions, and low incidence of reported adverse reactions. Future prospective studies should be undertaken to confirm the trends observed here.

The Role of Colonization in the Pathogenesis of Nosocomial Infections

The close relationship between colonization and the development of nosocomial infections has been demonstrated. Patient-related factors, such as underlying illness for all major sites of infection and advanced age, and pathogen-related factors, such as the ability of bacteria to adhere to epithelial cells, play the major roles in the pathogenesis of colonization. However, exact mechanisms of colonization have not been elucidated, and modulation of bacterial adherence as a method of infection prevention remains experimental. Current methods of infection prevention, therefore, focus either on preventing growth of colonizing microorganisms or on preventing patient-pathogen contact. Topical antibiotics have been used as a method of colonization prevention. However, their effectiveness may be limited by increases in antibiotic resistance; moreover, the effects on patient outcome are controversial. Maintenance of the physiologic mucosal environment using nonantimicrobial agents seems a promising approach, but only a few studies demonstrating efficacy have been published. Prevention of colonization still must rely heavily on basic infection control measures to prevent contact between patient and pathogen.

The Role of Colonization in the Pathogenesis of Nosocomial Infections

AbstractThe close relationship between colonization and the development of nosocomial infections has been demonstrated. Patient-related factors, such as underlying illness for all major sites of infection and advanced age, and pathogen-related factors, such as the ability of bacteria to adhere to epithelial cells, play the major roles in the pathogenesis of colonization. However, exact mechanisms of colonization have not been elucidated, and modulation of bacterial adherence as a method of infection prevention remains experimental. Current methods of infection prevention, therefore, focus either on preventing growth of colonizing microorganisms or on preventing patient-pathogen contact. Topical antibiotics have been used as a method of colonization prevention. However, their effectiveness may be limited by increases in antibiotic resistance; moreover, the effects on patient outcome are controversial. Maintenance of the physiologic mucosal environment using nonantimicrobial agents seems a promising approach, but only a few studies demonstrating efficacy have been published. Prevention of colonization still must rely heavily on basic infection control measures to prevent contact between patient and pathogen.