The Balance of CD8-Positive T Cells and PD-L1 Expression in the Myocardium Predicts Prognosis in Lymphocytic Fulminant Myocarditis.

INTRODUCTION: The clinical significance and prognostic value of T cell involvement and programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) have not been established in lymphocytic fulminant myocarditis (FM). We investigated the prognostic impact of the number of CD4+, CD8+, FoxP3+, and PD-1+ T cells, as well as PD-L1 expression, in cardiomyocytes in lymphocytic FM. METHODS: This is a single-center observational cohort study. Myocardial tissue was obtained from 16 consecutive patients at lymphocytic FM onset. The median follow-up was 140 days. Cardiac events were defined as a composite of cardiac death and left ventricular-assist device implantation. CD4, CD8, FoxP3, PD-1, and PD-L1 immunostaining were performed on myocardial specimens. RESULTS: The median age of the patients was 52 years (seven men and nine women). There was no significant difference in the number of CD4+ cells. The number of CD8+ cells and the CD8+/CD4+ T cell ratio were higher in the cardiac event group (Event+) than in the group without cardiac events (Event-) (p = 0.048 and p = 0.022, respectively). The number of FoxP3+ T cells was higher in the Event+ group (p = 0.049). Although there was no difference in the number of PD-1+ cells, cardiomyocyte PD-L1 expression was higher in the Event+ group (p = 0.112). Event-free survival was worse in the group with a high CD8+ cell count (p = 0.012) and high PD-L1 expression (p = 0.049). When divided into three groups based on the number of CD8+ cells and PD-L1 expression (CD8highPD-L1high [n = 8], CD8lowPD-L1high [n = 1], and CD8lowPD-L1low [n = 7]), the CD8highPD-L1high group demonstrated the worst event-free survival, while the CD8lowPD-L1high group had a favorable prognosis without cardiac events (p = 0.041). CONCLUSION: High myocardial expression of CD8+ T cells and PD-L1 may predict a poor prognosis in lymphocytic FM.

Efficacy of cefmetazole in immunocompetent patients with uncomplicated colonic diverticulitis: A propensity score matching analysis.

INTRODUCTION: The incidence of colonic diverticulitis is increasing in Japan. Although antimicrobial chemotherapy is a treatment option, Japanese guidelines for diverticulosis do not recommend any antibiotic in particular and antibiotic selection is left to the discretion of the prescribing physician, who often selects antibiotics with anti-pseudomonal activity. Therefore, this study compared the efficacy of cefmetazole (CMZ) with that of tazobactam/piperacillin (TAZ/PIPC) in hospitalized Japanese immunocompetent patients with uncomplicated colonic diverticulitis. PATIENTS AND METHODS: This retrospective study included Japanese immunocompetent patients hospitalized for colonic diverticulitis between April 2019 and March 2022. Participants were divided into the CMZ and TAZ/PIPC groups. After propensity score matching, the intergroup differences in clinical outcomes, including adverse events, mortality, and re-admission rate, were ascertained. RESULTS: During the study period, 142 Japanese patients were hospitalized with community-onset colonic diverticulitis; 124 of these patients were immunocompetent. Of the 124 patients, 42 were excluded, and the CMZ and TAZ/PIPC groups comprised 62 and 20 patients, respectively. After propensity score matching, there were 16 patients in each group. There was no significant intergroup difference in the mortality and re-admission rates; however, the incidence of liver dysfunction was significantly higher (p = 0.018) in the TAZ/PIPC group. CONCLUSION: In patients with colonic diverticulitis, CMZ therapy should be selected because of the adequate clinical outcomes and lower incidence of adverse events, as this would reduce broad-spectrum antibiotic use and minimize antibiotic-resistant bacteria.

Usefulness of bicarbonate-based Impella purge solution in a patient with heparin-induced thrombocytopenia: the first case report of long-term management in Japan.

Percutaneous mechanical circulatory support utilizing micro-axial flow pumps, such as the Impella group of devices, has become a life-saving technique in the treatment of refractory cardiogenic shock, with ever-increasing success rates. A 30-year-old man presented with acute decompensated heart failure and a severely reduced left ventricular ejection fraction (17%). Despite initial treatment with inotropic drugs and intra-aortic balloon pump support, his hemodynamic status remained unstable. Transition to Impella CP mechanical circulatory support was made on day 6 owing to persistently low systolic blood pressure. A significant decline in platelet count prompted suspicion of heparin-induced thrombocytopenia (HIT), later confirmed by positive platelet-activated anti-platelet factor 4/heparin antibody and a 4Ts score of 6 points. Argatroban was initially used as the purge solution, but owing to complications, a switch to Impella 5.0 and a bicarbonate-based purge solution (BBPS) was performed. Despite additional veno-arterial extracorporeal membrane oxygenation support on day 24, the patient, aiming for ventricular assist device treatment and heart transplantation, died from infection and multiple organ failure. Remarkably, the Impella CP continued functioning normally until the patient's demise, indicating stable Impella pump performance using BBPS. This case highlights the usefulness of BBPS as an alternative to conventional Impella heparin purge solution when HIT occurs.

Utilization of the modified Kama scoring system for predicting bail-out cholecystectomy: a valuable tool in the era of rising laparoscopic surgery prevalence.

PURPOSE: Recently, bail-out cholecystectomy (BOC) during laparoscopic cholecystectomy to avoid severe complications, such as vasculobiliary injury, has become widely used and increased in prevalence. However, current predictive factors or scoring systems are insufficient. Therefore, in this study, we aimed to test the validity of existing scoring systems and determine a suitable cutoff value for predicting BOC. METHODS: We retrospectively assessed 305 patients who underwent laparoscopic cholecystectomy and divided them into a total cholecystectomy group (n = 265) and a BOC group (n = 40). Preoperative and operative findings were collected, and cutoff values for the existing scoring systems (Kama's and Nassar's) were modified using a prospectively maintained database. RESULTS: The BOC rate was 13% with no severe complications. A logistic regression analysis revealed that the Kama's score (odds ratio, 0.93; 95% confidence interval 0.91-0.96; P < 0.01) was an independent predictor of BOC. A cutoff value of 6.5 points gave an area under the curve of 0.81, with a sensitivity of 87% and a specificity of 67%. CONCLUSIONS: Kama's difficulty scoring system with a modified cutoff value (6.5 points) is effective for predicting BOC.

Influence of dichroism on the optical properties of a twisted nematic liquid crystal cell in the terahertz region.

Polarization control is essential in terahertz (THz) imaging. Liquid crystals (LCs) have the potential to functionalize tunable polarization-control devices. Here, a twisted nematic (TN) cell using a hydrogen-bonded LC is fabricated, and the influence of dichroism in the THz region is discussed. Our results indicate that the polarization state in the Gooch-Tarry minimum condition is affected by the LC dichroism; a nondichroic LC is required for complete linearly polarized output. The output intensity of the dichroic LC-TN cell changed when electrically switched or when the incident THz wave polarization direction was rotated 90°. These intensity variations disappeared when using the nondichroic hydrogen-bonded LC.

An epidemiological evaluation of COVID-19 in La paz, Bolivia.

INTRODUCTION: The Plurinational State of Bolivia (Bolivia) has experienced four major waves of coronavirus disease 2019 (COVID-19) so far. Although the ministry of health has been tracking morbidity and mortality through each wave, epidemiology of COVID-19 in Bolivia is not well defined, despite a need for more accurate measurement of the number of cases and deaths to allow for forecasting of the pandemic. This study examined prevalence of COVID-19 at community level, determinants of its occurrence and vaccine effectiveness. METHODS: We conducted a cross-sectional study in La Paz city on 2,775 individuals between March 2020 and February 2022. A structured questionnaire was used to collect data on COVID-19 morbidity, mortality and vaccination status. RESULTS: Of the 2,775 participants, 1,586 (57.1%) were infected with COVID-19, and 187 (6.7%) were suspected cases. The mortality rate was 2.9%. Sinopharm, Johnson & Johnson, Gamaleya, Pfizer-BioNtech, Moderna and AstraZeneka vaccines are in use, and all vaccines have demonstrated effectiveness in reducing the risk of onset. Risk for mortality was significantly lower in the vaccinated group with an odds ratio of 0.037 (95％ confidential interval: 0.01-0.10, p-value: <0.001). CONCLUSIONS: Actual prevalence of COVID-19 in La Paz (the prevalence rate: 63.8%, including suspected case) was higher than that reported by the Ministry of Health and Sports in Bolivia (7.5%). In addition, vaccination has contributed significantly to the control of the COVID-19 epidemic in Bolivia. We believe that our report will be useful for COVID-19 prevention strategies in Bolivia for the future.

Increased risk of purge system malfunction after Impella 5.0 replacement: a case series.

The Impella 5.0 is an axial-flow percutaneous ventricular assist device used in patients with cardiogenic shock. Although the recommended period of use is 10 days or less, weaning can be delayed because of ongoing hemodynamic instability. In clinical practice, this device sometimes malfunctions during long-term management with heparin and must be replaced; however, the relationship between the duration of support with the initial and replacement Impella 5.0 and the changes in value of the purge system has not been fully elucidated. From July 2018 to May 2021, Impella 5.0 was implanted and used for more than 10 days in 11 patients at our institution. Four patients required Impella replacement because of device malfunction and the second Impella had purge system malfunction in all cases. The second Impella was used for a significantly shorter time than the first Impella (p = 0016). We calculated the ratio of purge pressure to purge flow rate and found that the ratio exceeded 50 mm Hg/mL/h in all cases with purge system malfunction. In conclusion, it is important to construct a treatment strategy considering the duration of use, because the risk of purge system malfunction is high after replaced Impella 5.0.

Synthesis of the matriglycan hexasaccharide, -3Xylα1-3GlcAß1-trimer and its interaction with laminin.

Matriglycan, a polysaccharide that is a pivotal part of the core M3 O-mannosyl glycan composed of the repeating disaccharide -3Xylα1-3GlcAß1-, interacts with laminin to stabilize muscle tissue. We herein report the synthesis of matriglycan-repeating hexasaccharides equipped with an alkyne linker to form glycoconjugates. The key step in the formation of an α-linked xylosyl glycoside was resolved by solvent-specific separation from an anomeric mixture. Successful glycan elongation was regio- and stereoselectively performed to obtain (-3Xylα1-3GlcAß1)3-O(C2H4O)3CH2CCH and the biotin conjugate. We also investigated interactions between matriglycan hexasaccharides and laminin-G-like domains 4 and 5 of laminin-α2 using saturation transfer difference-NMR. The dissociation constant obtained from bio-layer interferometry was estimated to be 7.5 × 10-8 M. These results indicate that a chemical approach may be applied to the reconstruction of muscle tissue.

Comparison of the empirical linear ablation and low voltage area-guided ablation in addition to pulmonary vein isolation in patients with persistent atrial fibrillation: a propensity score-matched analysis.

BACKGROUND: The efficacy of pulmonary vein isolation (PVI) alone is not guaranteed for persistent atrial fibrillation (PeAF), and it is unclear which type of ablation approach should be applied in addition to PVI. This study aimed to compare outcomes and prognosis between empirical linear ablation and low-voltage area (LVA) ablation after PVI for PeAF. METHODS: We enrolled 128 patients with PeAF who were assigned to the linear ablation group (n = 64) and the LVA ablation group (n = 64) using a propensity score-matched model. After PVI and cardioversion, the patients underwent either empirical linear ablation or LVA ablation during sinus rhythm. All patients in the linear ablation group underwent both roof line and mitral valve isthmus (MVI) ablations. An electrical-guided ablation targeting LVA (< 0.5 mV) was performed in the LVA group. When there was no LVA in the LVA group, only PVI was applied. We compared the procedural outcomes and recurrence after ablation between the two groups. RESULTS: The baseline characteristics were well-balanced between the two groups. Fifty patients had LVA (22 and 28 patients in the linear and LVA groups). The roof and MVI lines were completed in 100% and 96.9% of the patients. During the mean follow-up of 279.5 ± 161.3 days, the LVA group had significantly lower recurrence than the linear group (15 patients [23%] vs. 29 patients [45%], p = 0.014). Thirty-five patients were prescribed antiarrhythmic drugs during the follow-up period (linear group, n = 17; LVA group, n = 18); amiodarone and bepridil were administered to most of the patients (15 and 17 patients, respectively). The difference in the prognosis was relevant among the patients with LVA, while this trend was not observed in those without LVA. The LVA ablation group demonstrated significantly lower radiofrequency energy and shorter procedural time compared to the linear ablation group. The recurrence of atrial flutter was more likely to occur in the linear group than in the LVA group (14 [22%] vs. 6 [9.4%], p = 0.052). CONCLUSION: The electrophysiological-guided LVA ablation is more effective than empirical linear ablation in PeAF patients with LVA. Unnecessary empirical linear ablation might have a risk of iatrogenic gap and atrial flutter recurrence.

Prognostic value of malnutrition evaluated using the Global Leadership Initiative on Malnutrition criteria and its association with psoas muscle volume in non-ischemic dilated cardiomyopathy.

Heart failure (HF) is a systemic inflammatory disease that causes hypotrophy and skeletal muscle loss. The Global Leadership Initiative on Malnutrition (GLIM) criteria have been developed as a novel evaluation index for malnutrition, with reported usefulness in HF caused by ischemic heart disease. However, reports on the usefulness of malnutrition evaluated by the GLIM criteria in non-ischemic dilated cardiomyopathy (NIDCM) and its relationship with psoas muscle volume are lacking. We investigated the prognostic value of malnutrition evaluated using the GLIM criteria and its association with psoas muscle volume in patients with NIDCM. We enrolled 139 consecutive patients with NIDCM between December 2000 and June 2020. Malnutrition was evaluated using the GLIM criteria on admission. The median follow-up period was 4.7 years. Cardiac events were defined as a composite of cardiac death, hospitalization for worsening HF, and lethal arrhythmia. Furthermore, we measured the psoas muscle volume using computed tomography volumetry in 48 patients. At baseline, the median age was 50 years, and 132 patients (95.0%) had New York Heart Association functional class I or II HF. The median psoas muscle volume was 460.8 cm3. A total of 26 patients (18.7%) were malnourished according to the GLIM criteria. The Kaplan-Meier survival analysis showed that malnourished patients had more cardiac events than non-malnourished patients (log-rank, P < 0.001). The multivariate Cox proportional hazards regression analysis revealed that GLIM criteria-based malnutrition was an independent determinant of cardiac events (hazard ratio, 2.065; 95% confidence interval, 1.166-3.656; P = 0.014). Psoas muscle volume, which was assessed in a total of 48 patients, was lower in malnourished than in non-malnourished patients (median, 369.0 vs. 502.3 cm3; P = 0.035) and correlated with body mass index (r = 0.441; P = 0.002). Nutritional screening using the GLIM criteria may be useful in predicting future cardiac events in patients with NIDCM, reflecting a potential relationship between malnutrition and a low psoas muscle volume.

Segmental resection with partial mesopancreatic and mesojejunal excision (pMME) for duodenal carcinoma of the third or fourth portion.

INTRODUCTION: Pancreatoduodenectomy is the standard procedure for duodenal carcinoma of the third or fourth portion. As an alternative option, we developed a novel segmental resection (SR) with partial mesopancreatic and mesojejunal excision (pMME) that enhances radicality. In this report, the surgical technique with video and outcomes are described. METHOD: We performed SR with pMME on seven consecutive patients with third or fourth duodenal carcinoma between 2009 and 2021. We divided the procedure into four sections, including (1) wide Kocher's maneuver, (2) supracolic anterior artery-first approach, (3) dissection of the mesopancreas and mesojejunum, and (4) devascularization of the uncinate process and dissection of duodenum. RESULT: Median operative time was 348 min (range, 222-391 min), and median blood loss was 100 mL (range, 30-580 mL). Major complications of Clavien-Dindo classification grade 3a or more occurred in one patient. All patients achieved R0 resections with 10 mm or more proximal margin. Six cases (85%) were alive without recurrence. CONCLUSION: We developed a radical and safe procedure of SR with pMME as an alternative and less invasive approach for duodenal carcinoma of the third or fourth portion.

COVID-19 and Fatal Sepsis Caused by Hypervirulent Klebsiella pneumoniae, Japan, 2020.

A patient in Japan with coronavirus disease and hypervirulent Klebsiella pneumoniae K2 sequence type 86 infection died of respiratory failure. Bacterial and fungal co-infections caused by region-endemic pathogens, including hypervirulent K. pneumoniae in eastern Asia, should be included in the differential diagnosis of coronavirus disease patients with acutely deteriorating condition.

Immune response against SARS-CoV-2 in pediatric patients including young infants.

Pediatric cases of the coronavirus disease 2019 (COVID-19) are generally mild or asymptomatic, and are usually detected by virological examination following close contact with COVID-19 patients, often the children's parents. The detailed clinical features and virological data of pediatric patients with COVID-19, particularly young infants, remain unclear. Here, the clinical and virological characteristics of four children with COVID-19 including two young infants were investigated. One- and 4-month-old boys with COVID-19 were both asymptomatic, and seroconversion was demonstrated. These findings suggest that even young infants can mount an immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), despite having weaker immune defenses than adolescents and adults. Three-year-old boy, who was SARS-CoV-2-negative, was admitted to the same room as his SARS-CoV-2-positive father due to the lack of caregivers. Although he was asymptomatic, he had seroconverted to SARS-CoV-2. Eleven-year-old boy, who was sibling of the 3-year-old boy, was also SARS-CoV-2-negative. He was isolated in his own room and did not seroconvert. If young children are SARS-CoV-2 negative, they should be isolated from their SARS-CoV-2-positive parents. This may be difficult in practice, if parents with COVID-19 are the only available caregivers. In such situations, the most appropriate measures should be taken for each patient.

Regioselective Synthesis of Trisubstituted Quinoxalines Mediated by Hypervalent Iodine Reagents.

A facile and regioselective synthesis of quinoxalines, an important motif in medicinal chemistry and materials sciences, was developed. Despite their prospective utility, the regioselective preparation of trisubstituted quinoxalines has not been previously established. In the reported system, hypervalent iodine reagents catalyzed the annulation between α-iminoethanones and o-phenylenediamines in a chemo/regioselective manner to afford trisubstituted quinoxalines. Excellent regioselectivities (6:1 to 1:0) were achieved using [bis(trifluoroacetoxy)iodo]benzene and [bis(trifluoroacetoxy)iodo]pentafluorobenzene as annulation catalysts.

The role of the shell in core-shell-structured La-doped NaTaO3 photocatalysts.

NaTaO3, a semiconductor with a perovskite structure, has long been known as a highly active photocatalyst for overall water splitting when appropriately doped with La cations. A profound understanding of the surface feature and why and how it may control the water splitting activity is critical because redox reactions take place at the surface. One surface feature characteristic of La-doped NaTaO3 is a La-rich layer (shell) capping La-poor bulk (core). In this study, we investigate the role of the shell in core-shell-structured La-doped NaTaO3 through systematic chemical etching with an aqueous HF solution. We find that the La-rich shell plays a role in electron-hole recombination, electron mobility and water splitting activity. The shallow electron traps populating the La-rich shell trap the photoexcited electrons, decreasing their mobility. The shallowly trapped electrons remain reactive and are readily available on the surface to be extracted by the cocatalysts for the reduction reaction evolving H2. The presently employed chemical etching method also confirms the presence of a La concentration gradient in the core that regulates the steady-state electron population and water splitting activity. Here, we successfully reveal the nanoarchitecture-photoactivity relationship of core-shell-structured La-doped NaTaO3 that thereby allows tuning of the surface features and spatial distribution of dopants to increase the concentration of photoexcited electrons and therefore the water splitting activity. By recognizing the key factors that control the photocatalytic properties of a highly active catalyst, we can then devise proper strategies to design new photocatalyst materials with breakthrough performances.

[A Case of Immune-Related Adverse Events Affecting the Lungs, Skin, and Pituitary Gland during Pembrolizumab Treatment].

The patient was a 69-year-old man diagnosed with stage ⅣB lung adenocarcinoma with 95% programmed death- ligand 1 expression, and pembrolizumab monotherapy was initiated. The patient exhibited fatigue from the 12th course(36 weeks after treatment initiation) of treatment. Chest computed tomography revealed scattered ground-glass opacities in the upper lobes of both lungs, and he was subsequently diagnosed with interstitial pneumonia. Fatigue persisted even after a drug holiday from pembrolizumab, and the patient was diagnosed with hypopituitarism based on the results of endocrinological examinations. Rashes appeared on both legs 40 weeks after treatment initiation, which led to the patient being diagnosed with a drug-induced skin disorder. All the adverse events resolved upon treatment with hydrocortisone. Immune- related adverse events due to pembrolizumab may occur in multiple organs simultaneously.

Frequency and Mechanisms of Spontaneous Fosfomycin Nonsusceptibility Observed upon Disk Diffusion Testing of Escherichia coli.

Fosfomycin maintains activity against most Escherichia coli clinical isolates, but the growth of E. coli colonies within the zone of inhibition around the fosfomycin disk is occasionally observed upon susceptibility testing. We aimed to estimate the frequency of such nonsusceptible inner colony mutants and identify the underlying resistance mechanisms. Disk diffusion testing of fosfomycin was performed on 649 multidrug-resistant E. coli clinical isolates collected between 2011 and 2015. For those producing inner colonies inside the susceptible range, the parental strains and their representative inner colony mutants were subjected to MIC testing, whole-genome sequencing, reverse transcription-quantitative PCR (qRT-PCR), and carbohydrate utilization studies. Of the 649 E. coli clinical isolates, 5 (0.8%) consistently produced nonsusceptible inner colonies. Whole-genome sequencing revealed the deletion of uhpT encoding hexose-6-phosphate antiporter in 4 of the E. coli inner colony mutants, while the remaining mutant contained a nonsense mutation in uhpA The expression of uhpT was absent in the mutant strains with uhpT deletion and was not inducible in the strain with the uhpA mutation, unlike in its parental strain. All 5 inner colony mutants had reduced growth on minimal medium supplemented with glucose-6-phosphate. In conclusion, fosfomycin-nonsusceptible inner colony mutants can occur due to the loss of function or induction of UhpT but are rare among multidrug-resistant E. coli clinical strains. Considering that these mutants carry high biological costs, we suggest that fosfomycin susceptibility of strains that generate inner colony mutants can be interpreted on the basis of the zone of inhibition without accounting for the inner colonies.

Origin of the plasmid-mediated fosfomycin resistance gene fosA3.

Background: fosA3 is the most commonly reported plasmid-mediated fosfomycin resistance gene among Enterobacteriaceae. Objectives: To identify the origin of fosA3. Methods: The chromosome of Kluyvera georgiana clinical strain YDC799 was fully sequenced with single-molecule real-time sequencing. Comparative genetic analysis was performed for K. georgiana YDC799, K. georgiana type strain ATCC 51603 and representative fosA3-carrying plasmids. fosA genes were cloned in Escherichia coli to confirm function. Results: K. georgiana YDC799 harboured fosA (designated fosAKG) and blaCTX-M-8 on the chromosome. The genetic environments surrounding fosA3 and bounded by IS26 were nearly identical with the corresponding regions of K. georgiana YDC799 and ATCC 51603. The amino acid sequence of FosAKG from YDC799 and K. georgiana ATCC 51603 shared 99% and 94% identity with FosA3, respectively. Cloned FosAKG conferred fosfomycin resistance with an MIC of >1024 mg/L for E. coli. Conclusions: The plasmid-mediated fosA3 gene was likely mobilized from the chromosome of K. georgiana by an IS26-mediated event.

Inhibition of Fosfomycin Resistance Protein FosA by Phosphonoformate (Foscarnet) in Multidrug-Resistant Gram-Negative Pathogens.

FosA proteins confer fosfomycin resistance to Gram-negative pathogens via glutathione-mediated modification of the antibiotic. In this study, we assessed whether inhibition of FosA by sodium phosphonoformate (PPF) (foscarnet), a clinically approved antiviral agent, would reverse fosfomycin resistance in representative Gram-negative pathogens. The inhibitory activity of PPF against purified recombinant FosA from Escherichia coli (FosA3), Klebsiella pneumoniae (FosAKP), Enterobacter cloacae (FosAEC), and Pseudomonas aeruginosa (FosAPA) was determined by steady-state kinetic measurements. The antibacterial activity of PPF against FosA in clinical strains of these species was evaluated by susceptibility testing and time-kill assays. PPF increased the Michaelis constant (Km ) for fosfomycin in a dose-dependent manner, without affecting the maximum rate (Vmax) of the reaction, for all four FosA enzymes tested, indicating a competitive mechanism of inhibition. Inhibitory constant (Ki ) values were 22.6, 35.8, 24.4, and 56.3 µM for FosAKP, FosAEC, FosAPA, and FosA3, respectively. Addition of clinically achievable concentrations of PPF (∼667 µM) reduced the fosfomycin MICs by ≥4-fold among 52% of the K. pneumoniae, E. cloacae, and P. aeruginosa clinical strains tested and led to a bacteriostatic or bactericidal effect in time-kill assays among representative strains. PPF inhibits FosA activity across Gram-negative species and can potentiate fosfomycin activity against the majority of strains with chromosomally encoded fosA These data suggest that PPF may be repurposed as an adjuvant for fosfomycin to treat infections caused by some FosA-producing, multidrug-resistant, Gram-negative pathogens.