Antibiotic Failure Research Articles

Purine and pyrimidine synthesis differently affect the strength of the inoculum effect for aminoglycoside and β-lactam antibiotics.

If a bacterial population can grow and reach a sufficiently high density, routine doses of antibiotics can be ineffective. This phenomenon, called the inoculum effect, has been observed for nearly all antibiotics and bacterial species. It has also been reported to result in antibiotic failure in the clinic. Understanding how to reduce the inoculum effect can make high-density infections easier to treat. Here, we show that purine and pyrimidine synthesis affect the strength of the inoculum effect; as the transcriptional activity of pyrimidine synthesis increases, the strength of the inoculum effect for aminoglycosides decreases. Conversely, as the transcriptional activity of purine synthesis increases, the strength of the inoculum effect for β-lactam antibiotics decreases. Our work highlights the importance of nucleotide synthesis in determining the strength of the inoculum effect, which may lead to the identification of new ways to treat high-density infections in the clinic.

Review of: Contribution of the patient microbiome to surgical site infection and antibiotic prophylaxis failure in spine surgery

Review of: Contribution of the patient microbiome to surgical site infection and antibiotic prophylaxis failure in spine surgery

A MRSA mystery: how PBP4 and cyclic-di-AMP join forces against β-lactam antibiotics.

The high-level resistance to next-generation β-lactams frequently found in Staphylococcus aureus isolates lacking mec, which encodes the transpeptidase PBP2a traditionally associated with methicillin-resistant Staphylococcus aureus (MRSA), has remained incompletely understood for decades. A new study by Lai et al. found that the co-occurrence of mutations in pbp4 and gdpP, which respectively cause increased PBP4-mediated cell wall crosslinking and elevated cyclic-di-AMP levels, produces synergistic β-lactam resistance rivaling that of PBP2a-producing MRSA (L.-Y. Lai, N. Satishkumar, S. Cardozo, V. Hemmadi, et al., mBio 15:e02889-23. 2024, https://doi.org/10.1128/mbio.02889-23). The combined mutations are sufficient to explain the high-level β-lactam resistance of some mec-lacking strains, but the mechanism of synergy remains elusive and an avenue for further research. Importantly, the authors establish that co-occurrence of these mutations leads to antibiotic therapy failure in a Caenorhabditis elegans infection model. These results underscore the need to consider this unique and novel β-lactam resistance mechanism during the clinical diagnosis of MRSA, rather than relying on mec as a diagnostic.

Empirical antifungal therapy for health care-associated intra-abdominal infection: a retrospective, multicentre and comparative study

BackgroundCurrent guidelines recommend using antifungals for selected patients with health care-associated intra-abdominal infection (HC-IAI), but this recommendation is based on a weak evidence. This study aimed to assess the association between early empirical use of antifungals and outcomes in intensive care unit (ICU) adult patients requiring re-intervention after abdominal surgery.MethodsA retrospective, multicentre cohort study with overlap propensity score weighting was conducted in three ICUs located in three medical institutions in France. Patients treated with early empirical antifungals for HC-IAI after abdominal surgery were compared with controls who did not receive such antifungals. The primary endpoint was the death rate at 90 days, and the secondary endpoints were the death rate at 1 year and composite criteria evaluated at 30 days following the HC-IAI diagnosis, including the need for re-intervention, inappropriate antimicrobial therapy and death, whichever occurred first.ResultsAt 90 days, the death rate was significantly decreased in the patients treated with empirical antifungals compared with the control group (11.4% and 20.7%, respectively, p = 0.02). No differences were reported for the secondary outcomes.ConclusionThe use of early empirical antifungal therapy was associated with a decreased death rate at 90 days, with no effect on the death rate at 1 year, the death rate at 30 days, the rate of re-intervention, the need for drainage, and empirical antibiotic and antifungal therapy failure at 30 days.

Fever of unknown origin revealing testicular nocardiosis: a case report and literature review

BackgroundNocardia is an ubiquitous soil organism. As an opportunistic pathogen, inhalation and skin inoculation are the most common routes of infection. Lungs and skin are the most frequent sites of nocardiosis. Testis is a highly unusual location for nocardiosis.Case presentationWe report the case of an immunocompromised 75-year-old-man admitted for fever of unknown origin. He presented with skin lesions after gardening and was first suspected of Mediterranean spotted fever, but he did not respond to doxycycline. Then, physical examination revealed new left scrotal swelling that was compatible with a diagnosis of epididymo-orchitis. The patient’s condition did not improve despite empirical antibiotic treatment with the onset of necrotic scrotal abscesses requiring surgery. Nocardia brasiliensis yielded from the removed testis culture. High-dose trimethoprim-sulfamethoxazole and ceftriaxone were started. Multiple micro-abscesses were found in the brain and spinal cord on imaging studies. After 6 weeks of dual antibiotic therapy for disseminated nocardiosis, slight regression of the brain abscesses was observed. The patient was discharged after a 6-month course of antibiotics and remained relapse-free at that time of writing these lines. Trimethoprim-sulfamethoxazole alone is meant to be pursued for 6 months thereafter. We undertook a literature review on previously reported cases of genitourinary and urological nocardiosis; to date, only 36 cases have been published with predominately involvement of kidney, prostate and testis.ConclusionsTo the best of our knowledge, this is the first case of Nocardia brasiliensis simultaneously infecting skin, testis, brain and spinal cord in an immunocompromised patient. Knowledge on uncommon forms of nocardiosis remains scarce. This case report highlights the difficulty of diagnosing atypical nocardiosis and the importance of prompt bacteriological sampling in case of empirical antibiotics failure.

A Multicenter, Retrospective Outcome Analysis of Vancomycin Area Under the Curve versus Trough-Based Dosing Strategies in Patients with Burn OR Inhalational Injuries (MONITOR).

Vancomycin is a glycopeptide antibiotic that requires close therapeutic monitoring. Prolonged exposure to elevated concentrations increases risk for serious adverse effects such as nephrotoxicity. However, sub-therapeutic concentrations may lead to bacterial resistance and clinical failure or death. The most recent Infectious Diseases Society of America (IDSA) publication regarding therapeutic monitoring of vancomycin recommends utilizing area under the curve (AUC)-based monitoring to maximize clinical success. Despite the guideline recommendation for AUC-guided dosing, many institutions still use trough-only monitoring in their practices, including those caring for patients with acute burn injuries. Following burn injury, patients are at a higher risk for infections, multi-organ failure, and pharmacokinetic alterations. The primary objective of this multi-center retrospective study is to determine optimal therapeutic monitoring of vancomycin by comparing clinical success between AUC vs. trough-based monitoring in burn patients. MONITOR was a multicenter, retrospective study of patients with thermal or inhalation injury admitted to one of 13 burn centers from 1/1/17 to 8/31/22 who received vancomycin. Demographic and clinical course data, including acute kidney injury (AKI) incidence and clinical success were obtained. Patients were evaluated for clinical success and grouped according to method of monitoring and adjusting doses: AUC vs. trough-based monitoring. Clinical success was a composite definition and lack of meeting any 1 of 5 criteria: 1) persistent infection, 2) relapse, 3) antibiotic failure (clinical worsening), 4) AKI, 5) death. Five-hundred seventeen vancomycin courses were assessed from 485 patients. There was no difference in the rate of clinical success between AUC monitored and the trough-only monitored groups. Incidence of AKI was higher in the trough-only group; however, was not statistically significant after controlling for renal function on admission, past medical history of chronic kidney disease (CKD), and concomitant nephrotoxins.

3D Printed Multifunctional Biomimetic Bone Scaffold Combined with TP-Mg Nanoparticles for the Infectious Bone Defects Repair.

Infected bone defects are one of the most challenging problems in the treatment of bone defects due to the high antibiotic failure rate and the lack of ideal bone grafts. In this paper, inspired by clinical bone cement filling treatment, α-c phosphate (α-TCP) with self-curing properties is composited with β-tricalcium phosphate (β-TCP) and constructed a bionic cancellous bone scaffolding system α/β-tricalcium phosphate (α/β-TCP) by low-temperature 3D printing, and gelatin is preserved inside the scaffolds as an organic phase, and later loaded with a metal-polyphenol network structure of tea polyphenol-magnesium (TP-Mg) nanoparticles. The scaffolds mimic the structure and components of cancellous bone with high mechanical strength (>100MPa) based on α-TCP self-curing properties through low-temperature 3D printing. Meanwhile, the scaffolds loaded with TP-Mg exhibit significant inhibition of Staphylococcus aureus (S.aureus) and promote the transition of macrophages from M1 pro-inflammatory to M2 anti-inflammatory phenotype. In addition, the composite scaffold also exhibits excellent bone-enhancing effects based on the synergistic effect of Mg2+ and Ca2+. In this study, a multifunctional ceramic scaffold (α/β-TCP@TP-Mg) that integrates anti-inflammatory, antibacterial, and osteoinduction is constructed, which promotes late bone regenerative healing while modulating the early microenvironment of infected bone defects, has a promising application in the treatment of infected bone defects.

Assessing Clinician Utilization of Next-Generation Antibiotics Against Resistant Gram-Negative Infections in U.S. Hospitals : A Retrospective Cohort Study.

The U.S. antibiotic market failure has threatened future innovation and supply. Understanding when and why clinicians underutilize recently approved gram-negative antibiotics might help prioritize the patient in future antibiotic development and potential market entry rewards. To determine use patterns of recently U.S. Food and Drug Administration (FDA)-approved gram-negative antibiotics (ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, plazomicin, eravacycline, imipenem-relebactam-cilastatin, and cefiderocol) and identify factors associated with their preferential use (over traditional generic agents) in patients with gram-negative infections due to pathogens displaying difficult-to-treat resistance (DTR; that is, resistance to all first-line antibiotics). Retrospective cohort. 619 U.S. hospitals. Adult inpatients. Quarterly percentage change in antibiotic use was calculated using weighted linear regression. Machine learning selected candidate variables, and mixed models identified factors associated with new (vs. traditional) antibiotic use in DTR infections. Between quarter 1 of 2016 and quarter 2 of 2021, ceftolozane-tazobactam (approved 2014) and ceftazidime-avibactam (2015) predominated new antibiotic usage whereas subsequently approved gram-negative antibiotics saw relatively sluggish uptake. Among gram-negative infection hospitalizations, 0.7% (2551 [2631 episodes] of 362 142) displayed DTR pathogens. Patients were treated exclusively using traditional agents in 1091 of 2631 DTR episodes (41.5%), including "reserve" antibiotics such as polymyxins, aminoglycosides, and tigecycline in 865 of 1091 episodes (79.3%). Patients with bacteremia and chronic diseases had greater adjusted probabilities and those with do-not-resuscitate status, acute liver failure, and Acinetobacter baumannii complex and other nonpseudomonal nonfermenter pathogens had lower adjusted probabilities of receiving newer (vs. traditional) antibiotics for DTR infections, respectively. Availability of susceptibility testing for new antibiotics increased probability of usage. Residual confounding. Despite FDA approval of 7 next-generation gram-negative antibiotics between 2014 and 2019, clinicians still frequently treat resistant gram-negative infections with older, generic antibiotics with suboptimal safety-efficacy profiles. Future antibiotics with innovative mechanisms targeting untapped pathogen niches, widely available susceptibility testing, and evidence demonstrating improved outcomes in resistant infections might enhance utilization. U.S. Food and Drug Administration; NIH Intramural Research Program.

Contribution of the patient microbiome to surgical site infection and antibiotic prophylaxis failure in spine surgery.

Despite modern antiseptic techniques, surgical site infection (SSI) remains a leading complication of surgery. However, the origins of SSI and the high rates of antimicrobial resistance observed in these infections are poorly understood. Using instrumented spine surgery as a model of clean (class I) skin incision, we prospectively sampled preoperative microbiomes and postoperative SSI isolates in a cohort of 204 patients. Combining multiple forms of genomic analysis, we correlated the identity, anatomic distribution, and antimicrobial resistance profiles of SSI pathogens with those of preoperative strains obtained from the patient skin microbiome. We found that 86% of SSIs, comprising a broad range of bacterial species, originated endogenously from preoperative strains, with no evidence of common source infection among a superset of 1610 patients. Most SSI isolates (59%) were resistant to the prophylactic antibiotic administered during surgery, and their resistance phenotypes correlated with the patient's preoperative resistome (P = 0.0002). These findings indicate the need for SSI prevention strategies tailored to the preoperative microbiome and resistome present in individual patients.

Addressing Challenges in Wildlife Rehabilitation: Antimicrobial-Resistant Bacteria from Wounds and Fractures in Wild Birds.

Injuries and bone fractures are the most frequent causes of admission at wildlife rescue centers. Wild birds are more susceptible to open fractures due to their anatomical structure, which can lead to osteomyelitis and necrosis. Antibiotic therapy in these cases is indispensable, but the increase of antimicrobial-resistant isolates in wildlife has become a significant concern in recent years. In this context, the likelihood of antibiotic failure and death of animals with infectious issues is high. This study aimed to isolate, identify, and assess the antimicrobial resistance pattern of bacteria in wounds and open fractures in wild birds. To this end, injured birds admitted to a wildlife rescue center were sampled, and bacterial isolation and identification were performed. Then, antimicrobial susceptibility testing was assessed according to the disk diffusion method. In total, 36 isolates were obtained from 26 different birds. The genera detected were Staphylococcus spp. (63.8%), Escherichia (13.9%), Bacillus (11.1%), Streptococcus (8.3%), and Micrococcus (2.8%). Among Staphylococcus isolates, S. lentus and S. aureus were the most frequent species. Antimicrobial resistance was detected in 82.6% of the isolates, among which clindamycin resistance stood out, and 31.6% of resistant isolates were considered multidrug-resistant. Results from this study highlight the escalating scope of antimicrobial resistance in wildlife. This level of resistance poses a dual concern for wildlife: firstly, the risk of therapeutic failure in species of significant environmental value, and, secondly, the circulation of resistant bacteria in ecosystems.

Action of photodynamic inactivation in antibiotic failures

SignificanceThe increase in the number of microorganisms resistant to antimicrobials motivates the search for strategies that recover the use of traditional antibiotics. Photodynamic Inactivation (PDI) is an alternative to antibiotics because the combination of a photosensitizer with light leads to the production of reactive oxygen species that promote the elimination of undesirable cells. ApproachCurcumin and light at 450 nm are applied at regular intervals and new values of minimum inhibitory concentration of antibiotics are obtained. ResultsWe demonstrated that the application of PDI reduces the necessary dosage of antibiotics for the elimination of the bacterial cell, proving to be an efficient strategy for application in resistant strains. Furthermore, we verified that the interaction of the photosensitizer with the antibiotics promotes alterations in the metabolism and the bacterial biomolecules. ConclusionsThese results are essential to transfer in vitro studies to the clinical implementation of DIF as an adjuvant to antibiotic therapy.

Action of photodynamic inactivation in antibiotic failures

SignificanceThe increase in the number of microorganisms resistant to antimicrobials motivates the search for strategies that recover the use of traditional antibiotics. Photodynamic Inactivation (PDI) is an alternative to antibiotics because the combination of a photosensitizer with light leads to the production of reactive oxygen species that promote the elimination of undesirable cells. ApproachCurcumin and light at 450 nm are applied at regular intervals and new values of minimum inhibitory concentration of antibiotics are obtained. ResultsWe demonstrated that the application of PDI reduces the necessary dosage of antibiotics for the elimination of the bacterial cell, proving to be an efficient strategy for application in resistant strains. Furthermore, we verified that the interaction of the photosensitizer with the antibiotics promotes alterations in the metabolism and the bacterial biomolecules. ConclusionsThese results are essential to transfer in vitro studies to the clinical implementation of DIF as an adjuvant to antibiotic therapy.

Antimicrobial Activity of Bacillus amyloliquefaciens BS4 against Gram-Negative Pathogenic Bacteria.

Worldwide, bacterial resistance is one of the most severe public health problems. Currently, the failure of antibiotics to counteract superbugs highlights the need to search for new molecules with antimicrobial potential to combat them. The objective of this research was to evaluate the antimicrobial activity of Bacillus amyloliquefaciens BS4 against Gram-negative bacteria. Thirty yeasts and thirty-two Bacillus isolates were tested following the agar well-diffusion method. Four Bacillus sp. strains (BS3, BS4, BS17, and BS21) showed antagonistic activity against E. coli ATCC 25922 using bacterial culture (BC) and the cell-free supernatant (CFS), where the BS4 strain stood out, showing inhibitory values of 20.50 ± 0.70 mm and 19.67 ± 0.58 mm for BC and CFS, respectively. The Bacillus sp. BS4 strain can produce antioxidant, non-hemolytic, and antimicrobial metabolites that exhibit activity against several microorganisms such as Salmonella enterica, Klebsiella pneumoniae, Shigella flexneri, Enterobacter aerogenes, Proteus vulgaris, Yersinia enterocolitica, Serratia marcescens, Aeromonas sp., Pseudomonas aeruginosa, Candida albicans, and Candida tropicalis. According to the characterization of the supernatant, the metabolites could be proteinaceous. The production of these metabolites is influenced by carbon and nitrogen sources. The most suitable medium to produce antimicrobial metabolites was TSB broth. The one-factor-at-a-time method was used to standardize parameters such as pH, agitation, temperature, carbon source, nitrogen source, and salts, resulting in the best conditions of pH 7, 150 rpm, 28 °C, starch (2.5 g/L), tryptone (20 g/L), and magnesium sulfate (0.2 g/L), respectively. Moreover, the co-culture was an excellent strategy to improve antimicrobial activity, achieving maximum antimicrobial activity with an inhibition zone of 21.85 ± 1.03 mm. These findings position the Bacillus amyloliquefaciens BS4 strain as a promising candidate for producing bioactive molecules with potential applications in human health.

Characterization of a new Pseudomonas aeruginosa Queuovirinae bacteriophage.

The ESKAPEE pathogen Pseudomonas aeruginosa is a common cause of chronic wound and cystic fibrosis lung infections, as well as acute burn and nosocomial infections. Many of these infections are recalcitrant to conventional antibiotic therapies due to both traditional antibiotic resistance mechanisms and antimicrobial tolerance. Recent successes with bacteriophage (phage) therapy to treat chronic human P. aeruginosa infections have led to a renewed interest in isolating and characterizing new P. aeruginosa phages. Here, we isolated and characterized a new lytic phage (termed PIP, pili-infecting phage) capable of infecting P. aeruginosa PA14. PIP is a tailed phage with an icosahedral head and flexible tail containing a genome that is 57,462 bp in length. Phylogenetic analysis reveals that PIP belongs to the subfamily Queuovirinae and genus Nipunavirus but is highly divergent in gene content from known Nipunaviruses. By isolating and characterizing a P. aeruginosa strain that spontaneously evolved resistance to PIP, we show that the receptor for PIP is Type IV pili. In summary, we isolated a new P. aeruginosa phage species with a unique genome, thus increasing the diversity of phages known to infect this important human pathogen.IMPORTANCEThe opportunistic pathogen Pseudomonas aeruginosa causes both acute and chronic human infections. These infections are notoriously difficult to treat due to both antibiotic resistance and antibiotic tolerance. The increasing frequency of antibiotic failure in P. aeruginosa infections has led scientists to explore other treatment options, including bacteriophage (phage) therapy. To this end, there has been a significant effort to identify new Pseudomonas phages. Here, we isolated and characterized a bacteriophage (termed PIP, pili-infecting phage) that infects P. aeruginosa PA14. Examination of the PIP genome revealed that this phage represents a new species in the subclass Queuovirinae. The isolation and characterization of spontaneous PA14 mutants that are resistant to PIP infection revealed Type IV pili as the PIP receptor. Ultimately, this study characterizes a new species of Pseudomonas phage, thus enhancing the known diversity of phages that infect this important pathogen.

Prevalence of heteroresistant Helicobacter pylori and treatment follow-up in patients in Ilam, Iran.

Special antibiotics are prescribed against Helicobacter (H.) pylori. However, sometimes the bacteria are not completely eliminated, or they are recurrent. Unlike most infections, it is very difficult to eliminate a H. pylori infection. Heteroresistance is defined as the phenomenon in which subpopulations of the same colony of bacteria exhibit a range of susceptibilities to a particular antibiotic. Because of heteroresistant cells, antibiotic failure and chronic infection can occur; thus, the current research aimed to investigate presence of heteroresistant cells in H. pylori collected from patients reffering to clinic in Ilam, Iran. Subsequently, patients who were infected with heteroresistant H. p ylori were treated with antibiotics effective against heteroresistant subpopulations. In this cross-sectional descriptive study, 100 patients with clinical symptoms and suspected of being infected with H. pylori were studied in private clinics in Ilam, Iran. Fiftyisolates of H. pylori accompanied by patients' information were obtained from Ilam clinics. We cultured the bacteria to identify heteroresistance and to find the cause of recurrent infection in these patients. Out of a total of 50 samples, 3 were heteroresistant to clarithromycin (6%). Levofloxacin was applied in cases of heteroresistant samples, and the effectiveness was determined after one month of follow-up of patients. Patients with heteroresistance showed sensitivity to levofloxacin. After one month of follow-up, it was found that the effectiveness of this antibiotic was good. Therefore, this antibiotic was introduced as a more effective drug in patients with heteroresistant H. pylori.

Investigating the Effectiveness of mqsR-Peptide Nucleic Acid as a Novel Solution for the Eradication of Persister Cells in Clinical Isolates of Escherichia coli.

Bacterial persisters are non- or slow-growing phenotypic variants that may be responsible for recalcitrance and relapse of persistent infections and antibiotic failure. In Escherichia coli, mqsRA is a well-known type II toxin-antitoxin system associated with persister cell formation. This study aimed to investigate the efficiency of an antisense peptide nucleic acid (PNA) targeting mqsRA in eliminating E. coli persisters. The study included 600 non-duplicated urine samples from adult patients with suspected urinary tract infections. The isolates were subjected to antimicrobial susceptibility testing and bacterial persister cells assay. The presence of mqsRA in the isolates was evaluated by polymerase chain reaction. Finally, expression of the mqsR and mqsA genes was assessed after exposure to normal conditions, stress, and different concentrations of mqsR-PNA (1 - 35 μM). The mqsR gene was significantly overexpressed under stress conditions, which was compensated by the PNA treatment. Complete inhibition of E. coli persister cells was achieved after overnight treatment with the anti-mqsR-PNA at concentrations ≥ 15 μM. The growth of E. coli persister cells can be inhibited by the anti-mqsR-PNA. Further studies are required to evaluate the effectiveness of this antisense PNA in both preclinical and clinical settings.

Utilization of experimental and theoretical piezoresponse of BTO nanocrystal for rapid decomposition of the pathogenic coliform bacteria

Currently, more attention is being paid to new and innovative techniques for combating issues like the emergence of multidrug-resistant strains (MDRs), the proliferation of biofilms, and the failure of antibiotics. In order to combat this, scientists are nowadays exploring different activable and responsive materials. Nano-sized barium titanate is a material that has an excellent piezo-responsive nature. The synthesis of perovskite barium titanate (BTO) nanoparticles by a nonconventional solvothermal method with exceptional piezo and ferroelectric properties is reported in this work. The synthesized BTO nanoparticles were well-characterized using different tools such as XRD, FTIR, TGA, electron microscopy, and UV–Vis spectroscopy, and the microstructure was analyzed using theoretical Rietveld refinement studies to substantiate the proper formation of the BTO nanostructure. Two different phases of BTO nanoparticles are observed after the refinement. Then, the piezoelectric effectiveness was further estimated by theoretical density functional theory (DFT) calculation. The catalytic behavior of the nanoparticles in bacteria has been studied for the degradation of Gram-negative Escherichia coli and Gram-positive Enterococcus faecalis cells using an ultrasonically driven piezocatalytic effect. A promising value in bacterial eradication was depicted by the antibacterial efficacy observed herein, with a few minutes of soft ultrasound (15 kHz) generating an enormous number of reactive radicals (ROS). The result of this study could aid in generating new dimensions in antibacterial therapy.

Zwitterion modified cochlear implants resist postoperative infection and inflammation

The cochlear implant (CI), an advanced electronic device replacing the entire cochlear function, is the ultimate treatment for over 466 million people with disabling hearing loss. Infection after cochlear implantation is a common and worrisome complication despite the routine administration of the antibiotic. The bacterial biofilms formed on the surface of CI are the main cause of antibiotic failure. To solve this problem, we developed a copper-containing zwitterionic coating consisting of anti-adherent poly sulfobetaine methacrylate (PSB) and steadfast polydopamine (PDA). CuSO4/H2O2. was added to accelerate this co-deposition reaction and enhance the anti-bacterial property. The preparation method was simple, rapid, and suitable for clinical use. In our in vitro and in vivo studies, the PSB/PDA(Cu) coating showed high biocompatibility, and conferred CI implants excellent anti-inflammatory, strong anti-bacterial effects, and great anti-biofilm properties to representative Gram-positive and Gram-negative bacteria. These findings implied that the PSB/PDA(Cu) coating was a unique anti-bacterial strategy for enhancing CI performance.

Stapled Phd Peptides Inhibit Doc Toxin Induced Growth Arrest in Salmonella.

Bacterial toxin inhibition is a promising approach to overcoming antibiotic failure. InSalmonella, knockout of the toxin Doc has been shown to significantly reduce the formation of antibiotic-tolerant persisters. Doc is a kinase that is inhibited in nontolerant cells by its cognate antitoxin, Phd. In this work, we have developed first-in-class stapled peptide antitoxin mimetics based on the Doc inhibitory sequence of Phd. After making a series of substitutions to improve bacterial uptake, we identified a lead stapled Phd peptide that is able to counteract Doc toxicity in Salmonella. This provides an exciting starting point for the further development of therapeutic peptides capable of reducing antibiotic persistence in pathogenic bacteria.

Morganella morganii and Enterococcus faecalis endophthalmitis following intravitreal injection

BackgroundEndophthalmitis following intravitreal injection is a potentially devastating complication of anti-VEGF injections. Post-injection endophthalmitis due to Enterococcus faecalis is rare, and no previous case of Morganella morganii endophthalmitis after intravitreal injection has been reported.Case presentationWe present the first reported case of Morganella morganii and Enterococcus faecalis endophthalmitis after intravitreal injection in an immunocompetent patient in the absence of recent ocular surgery. Our patient presented with hand movement visual acuity one day after anti-VEGF injection and demonstrated no clinical improvement despite repeated intravitreal ceftazidime and vancomycin injections. A decision was made to proceed with early vitrectomy given failure of intravitreal antibiotics. Visual acuity improved to 6/90 at 12 weeks after vitrectomy without any evidence of disease recurrence.ConclusionsPost-injection endophthalmitis due to concurrent Morganella morganii and Enterococcus faecalis infections can have visually devastating consequences despite repeated empirical and targeted intravitreal antibiotics. Lack of clinical improvement following intravitreal antibiotics should warrant consideration of early vitrectomy. Our experience is a pertinent reminder of the ever-growing threat of uncommon and multi-resistant bacteria that must be considered when treating infections such as post-injection endophthalmitis.