Tubal factor infertility (TFI) represents 36% of female infertility and genital infection by Chlamydia trachomatis (C. trachomatis) is a major cause. Although TFI is associated with host inflammatory responses to bacterial components, the molecular pathogenesis of Chlamydia-induced infertility remains poorly understood. We investigated the hypothesis that activation of specific cysteine proteases, the caspases, during C. trachomatis genital infection causes the disruption of key fertility-promoting molecules required for embryo development and implantation. We analyzed the effect of caspase inhibition on infertility and the integrity of Dicer, a caspase-sensitive, fertility-promoting ribonuclease III enzyme, and key micro-RNAs in the reproductive system. Genital infection with the inflammation- and caspase-inducing, wild-type C. trachomatis serovar L2 led to infertility, but the noninflammation-inducing, plasmid-free strain did not. We confirmed that caspase-mediated apoptotic tissue destruction may contribute to chlamydial pathogenesis. Caspase-1 or -3 deficiency, or local administration of the pan caspase inhibitor, Z-VAD-FMK into normal mice protected against Chlamydia-induced infertility. Finally, the oviducts of infected infertile mice showed evidence of caspase-mediated cleavage inactivation of Dicer and alteration in critical miRNAs that regulate growth, differentiation, and development, including mir-21. These results provide new insight into the molecular pathogenesis of TFI with significant implications for new strategies for treatment and prevention of chlamydial complications.

Pseudomonas aeruginosa is intrinsically resistant to many antimicrobial drugs, making carbapenems crucial in clinical management. During July–October 2015 in the United States, we piloted laboratory-based surveillance for carbapenem-resistant P. aeruginosa (CRPA) at sentinel facilities in Georgia, New Mexico, Oregon, and Tennessee, and population-based surveillance in Monroe County, NY. An incident case was the first P. aeruginosa isolate resistant to antipseudomonal carbapenems from a patient in a 30-day period from any source except the nares, rectum or perirectal area, or feces. We found 294 incident cases among 274 patients. Cases were most commonly identified from respiratory sites (120/294; 40.8%) and urine (111/294; 37.8%); most (223/280; 79.6%) occurred in patients with healthcare facility inpatient stays in the prior year. Genes encoding carbapenemases were identified in 3 (2.3%) of 129 isolates tested. The burden of CRPA was high at facilities under surveillance, but carbapenemase-producing CRPA were rare.

We report on a carbapenemase-producing hypervirulent Klebsiella pneumoniae (CP-hvKP) isolate collected from a U.S. patient at an outpatient clinic. The isolate was identified as K. pneumoniae serotype K1 sequence type 23 and included both a hypervirulence (with rmpA, rmpA2 iroBCDN, peg-344, and iucABCD-iutA genes) and a carbapenemase-encoding (bla KPC-2 ) plasmid. The emergence of CP-hvKP underscores the importance of clinical awareness of this pathotype and the need for continued monitoring of CP-hvKP in the United States.

Glandular odontogenic cyst (GOC) is an extremely rare lesion occurring in the jawbones. The present paper is a review of 181 cases of GOCs reported in English literature, since it was first reported by Padayache and Van Wyk in 1987. Mandible was involved in 130 cases and maxilla in 51 cases. Anterior mandible was the most common area of involvement. Radiographic appearance was that of a unilocular radiolucency in 98 of 176 reported cases. Rest presented as multilocular radiolucency. Cortical expansion was observed in 136 of the 180 reported cases while cortex breach or perforation was seen in 81 cases. The treatment of choice was that of minor procedures that included enucleation with or without curettage, peripheral ostectomy, cryotherapy, etc. in 157 of the total 177 reported cases. Marginal jaw resection, segmental mandibulectomy etc. was reported in 20 cases. Although minor surgical procedures were the treatment of choice in most studies, two major studies of Kaplan et al. and Fowler et al. involving 111 and 46 cases, recorded a recurrence rate of 35.9 and 19.6%, respectively. The age range was between 11 and 82 years. The respective mean age of patients in the above mentioned studies was 45.7 for Kaplan's and 51 years for Fowler's whereas in our study, the mean age was 45.9 years. Very rarely does GOC presents itself in a paediatric patient. The paper also reports a case of an 11-year-old child whose histopathogy came out to be a case of a GOC.

Carbapenem-resistant Enterobacterales (CRE) are a growing public health concern due to resistance to multiple antibiotics and potential to cause health care-associated infections with high mortality. Carbapenemaseproducing CRE are of particular concern given that carbapenemase-encoding genes often are located on mobile genetic elements that may spread between different organisms and species. In this study, we performed phenotypic and genotypic characterization of CRE collected at eight U.S. sites participating in active population-and laboratory-based surveillance of carbapenem-resistant organisms. Among 421 CRE tested, the majority were isolated from urine (n = 349, 83%). Klebsiella pneumoniae was the most common organism (n = 265, 63%), followed by Enterobacter cloacae complex (n = 77, 18%) and Escherichia coli (n = 50, 12%). Of 419 isolates analyzed by whole genome sequencing, 307 (73%) harbored a carbapenemase gene; variants of bla KPC predominated (n = 299, 97%). The occurrence of carbapenemase-producing K. pneumoniae, E. cloacae complex, and E. coli varied by region; the predominant sequence type within each genus was ST258, ST171, and ST131, respectively. None of the carbapenemase-producing CRE isolates displayed resistance to all antimicrobials tested; susceptibility to amikacin and tigecycline was generally retained.

The treatment of infections caused by carbapenem-resistant Enterobacterales, especially New Delhi metallo-β-lactamase (NDM)-producing bacteria, is challenging. Although less common in the United States than some other carbapenemase-producers, NDM-producing bacteria are a public health threat due to the limited treatment options available. Here we report on the antibiotic susceptibility of 275 contemporary NDM-producing Enterobacterales collected from 30 U.S. states through the Centers for Disease Control and Prevention's Antibiotic Resistance Laboratory Network. The aim of the study was to determine the susceptibility of these isolates against 32 currently available antibiotics using reference broth microdilution and explore the in vitro activity of 3 combination agents that are not yet available. Categorical interpretations were determined using Clinical and Laboratory Standards Institute (CLSI) interpretative criteria. For agents without CLSI criteria, Food and Drug Administration (FDA) interpretative criteria were used. The percentage of susceptible isolates did not exceed 90% for any of the FDA-approved antibiotics tested. The antibiotics with breakpoints that had the highest in vitro activity were tigecycline (86.5% susceptible), eravacycline (66.2% susceptible), and omadacycline (59.6% susceptible) 18.2% of isolates were susceptible to aztreonam. All NDM-producing isolates tested were multidrug-resistant, and 116 isolates were extensively drug-resistant (42.2%) 207 (75.3%) isolates displayed difficult-to-treat resistance. The difficulty in treating infections caused by NDM-producing Enterobacterales highlights the need for containment and prevention efforts to keep these infections from becoming more common.

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