Activity of Cefiderocol Against Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii Endemic to Medical Centers in New York City.

Therapeutic options for the treatment of infections owing to multidrug-resistant Gram-negative pathogens are often limited. Cefiderocol is a novel siderophore cephalosporin with activity against Gram-negative pathogens, including many multidrug-resistant strains. The activity of cefiderocol was examined against Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii that included (1) a recent surveillance collection of clinical isolates, (2) a collection of carbapenem-resistant isolates from a previous surveillance study, and (3) a collection of well-characterized isolates. Susceptibility testing for cefiderocol was performed with iron-depleted cation-adjusted Mueller-Hinton broth. Cefiderocol minimum inhibitory concentrations (MICs) were correlated with resistance mechanisms in the well-characterized isolates. For the Enterobacterales, including a collection of KPC-possessing Klebsiella pneumoniae, cefiderocol MICs were all ≤4 mg/L. Cefiderocol MICs were two- to fourfold higher in cephalosporin-resistant isolates. For K. pneumoniae, MICs did not correlate with expression of genes encoding porins or efflux systems. For P. aeruginosa, >99% of isolates were inhibited by ≤4 mg/L, including the collection of carbapenem-resistant isolates. For P. aeruginosa, cefiderocol activity was not affected by expression of ampC, oprD, or several efflux systems. All the surveillance isolates of A. baumannii, and 88% of the collection of carbapenem-resistant isolates, had cefiderocol MICs ≤4 mg/L. MICs were twofold higher in A. baummannii isolates with proven extended-spectrum beta-lactamases, and cefiderocol activity did not correlate with expression of efflux systems. Cefiderocol demonstrated potent activity against important nosocomial pathogens. Continued development of this agent as a therapeutic option against multidrug-resistant bacteria should be encouraged.

Emergence of Delafloxacin-Resistant Staphylococcus aureus in Brooklyn, New York.

Delafloxacin is an option for infections due to methicillin-resistant Staphylococcus aureus. In 2017, 22% of isolates from 7 hospitals in Brooklyn, New York, were nonsusceptible to delafloxacin. Isolates belonging to ST105, a strain associated with healthcare-related infections, predominated. Resistance was also found in ST8, a strain (USA300) associated with community-associated infections.

Activity of Meropenem with a Novel Broader-Spectrum ß-Lactamase Inhibitor, WCK 4234, against Gram-Negative Pathogens Endemic to New York City.

WCK 4234 is a novel diazabicyclooctane with potent inhibitory activity against class A and D carbapenemases and class C enzymes. We examined the in vitro activity of meropenem plus WCK 4234 (4 or 8 µg/ml) against Gram-negative pathogens from New York City. Three groups of isolates were analyzed: a contemporary collection of isolates, a collection of known carbapenem-resistant isolates, and a collection of isolates with defined resistance mechanisms. From the contemporary collection, we found (i) that all Enterobacteriaceae were susceptible to meropenem plus WCK 4234, (ii) that susceptibility rates for Acinetobacter baumannii were 56.5% for meropenem alone, 82.6% with 4 µg/ml WCK 4234, and 95.7% with 8 µg/ml WCK 4234, and (iii) that WCK 4234 had a modest effect on susceptibility of Pseudomonas aeruginosa Against a collection of carbapenem-resistant isolates, the addition of WCK 4234 to meropenem (i) restored meropenem susceptibility against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates, (ii) improved susceptibility against A. baumannii, and (iii) had a negligible effect against P. aeruginosa When tested against isolates with defined mechanisms of resistance, MICs of meropenem plus WCK 4234 were higher for K. pneumoniae with blaKPC albeit well below the susceptibility breakpoint; efflux systems or porins did not correlate with susceptibility. For A. baumannii, MICs of meropenem plus WCK 4234 did not correlate with efflux systems, outer membrane protein, blaampC, or blaoxa-51; however, MICs were higher in isolates with extended-spectrum ß-lactamases (ESBLs). For P. aeruginosa, isolates with relatively higher MICs of meropenem plus WCK 4234 had increased expression of ampC WCK 4234 is a potent ß-lactamase inhibitor that, when combined with meropenem, displays promising activity against multidrug-resistant pathogens.

Activity of cefepime/zidebactam (WCK 5222) against Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii endemic to New York City medical centres.

BACKGROUND: The combination of cefepime and zidebactam (WCK5222), a novel ß-lactam enhancer, has demonstrated activity against a wide variety of Gram-negative pathogens and is currently under clinical evaluation. OBJECTIVES: To examine the activity of cefepime/zidebactam against: (i) a contemporary collection of Gram-negative isolates from New York City; (ii) a collection of carbapenem-resistant clinical isolates; and (iii) a collection of isolates with characterized resistance mechanisms. METHODS: Susceptibility tests were performed using broth microdilution for cefepime, zidebactam and cefepime/zidebactam (1:1). RESULTS: More than 99% of a contemporary collection of Escherichia coli, Klebsiella pneumoniae and Enterobacter spp. had cefepime/zidebactam MICs ≤2 mg/L, the susceptibility breakpoint for cefepime. For K. pneumoniae, the acquisition of blaKPC resulted in increased MICs, although MICs remained ≤2 mg/L for 90% of KPC-possessing isolates. Overall for Pseudomonas aeruginosa, 98% of isolates had MICs ≤8 mg/L and MICs were affected by increased expression of ampC. For carbapenem-resistant P. aeruginosa, 78% of isolates had cefepime/zidebactam MICs ≤8 mg/L. The activity of cefepime/zidebactam against Acinetobacter baumannii was lower, with 85% of all isolates and 34% of carbapenem-resistant isolates with MICs ≤8 mg/L (cefepime interpretative criteria). CONCLUSIONS: Cefepime/zidebactam demonstrated excellent activity against Enterobacteriaceae and P. aeruginosa, although activity was reduced in carbapenem-non-susceptible isolates. The activity against A. baumannii was reduced and studies examining the therapeutic efficacy in strains with high cefepime/zidebactam MICs are warranted.

Predictors and patterns of melanoma recurrence following a negative sentinel lymph node biopsy.

To analyse the patient demographics, tumour characteristics and follow-up data of patients with recurrence of melanoma following a negative sentinel lymph node biopsy. A retrospective review of a prospectively maintained melanoma database was conducted. Melanoma patients who had a negative sentinel lymph node were identified and we performed statistical analysis on their respective demographics, tumour histology characteristics and follow-up data. Of 164 patients studied, 40 (24%) had a recurrence of melanoma at a median of 39.5 months following diagnosis (range 1-92 months). Distant metastases were the most common form of disease recurrence (40% of all recurrences). Increasing tumour thickness was an independent predictor of recurrence on multivariate analysis while nodular histology approached significance. Median survival of 6 months was seen following disease recurrence (range 1-126 months). In the setting of a negative sentinel lymph node biopsy, there remains a risk of melanoma recurrence. Distant metastases were the most common form of recurrence. Disease recurrence occurred more frequently in those with thick primary tumours. Recurrences occurred at long intervals from diagnosis indicating the need to consider prolonged patient follow-up.

Squamous cell carcinoma of the prostate following treatment with an LHRH-agonist: a rare case of transformation of adenocarcinoma of the prostate.

Squamous cell carcinoma (SCC) is a rare variant of prostate cancer. We report a case of a patient who was diagnosed with metastatic adenocarcinoma of the prostate, treated with leuprorelin and subsequently found to have SCC 18 months later. We have found one case in the literature with a similar scenario of possible transformation of adenocarcinoma to SCC secondary to luteinizing hormone-releasing hormone (LHRH) treatment. We found interesting similarities between the two cases, which raise the possibility of the transformation of tumour type and highlights the importance of the clinical picture in the follow-up, even with low prostate specific antigen (PSA) value.

Pilonidal sinus cyst of the penis: a rare manifestation of a common disease.

Pilonidal sinus is a chronic inflammatory condition owing to the subcutaneous trapping of hair. Most commonly it is found in the sacrococcygeal region (natal cleft) but rarely it is found on the penis with very few cases reported in the literature worldwide. We are reporting a case of a pilonidal sinus growing on the distal penile shaft with the sinus opening to the mucosal layer of the foreskin, in a young and fit patient. The cyst was removed with a circumcision and found to contain hair. This was confirmed by histology as a pilonidal sinus cyst.

Idiopathic spontaneous rupture of the urinary bladder (SRUB). A case report and review of literature.

Spontaneous rupture of the urinary bladder (SRUB) is a rare urological emergency. It is usually secondary to an underlying pathology. An idiopathic entity has not been reported in the literature. We report a case of idiopathic SRUB in a young female presented with abdominal pain and acute renal injury in the absence of prior trauma. We have conducted a literature review to identify commonly reported etiologies. SRUB is usually secondary to an underlying pathology, but in extremely rare cases it can be idiopathic.

Oligomerization of the human ARF tumor suppressor and its response to oxidative stress.

The tumor suppressor ARF plays an important role as an inhibitor of the Mdm2-mediated degradation of p53. Here we demonstrate that human ARF (p14ARF) can form homo-oligomers. The stability of the oligomers is favored by oxidizing agents in a reversible fashion and involves all three cysteine residues in p14ARF. Furthermore, the effect of p14ARF in clonogenic assays is moderately but reproducibly increased by the mutation of its cysteine residues. We also observed that altering the amino terminus of p14ARF resulted in the appearance of remarkably stable oligomers. This indicates that the amino terminus of p14ARF interferes with the ability of the protein to form multimeric complexes. These observations suggest that p14ARF activity may be linked to its oligomerization status and sensitive to the redox status of the cell.