The in vitro activities of TP-271, a novel fluorocycline antimicrobial, against 22 isolates of Mycobacterium abscessus, 22 isolates of Mycobacterium fortuitum, and 19 isolates of Nocardia spp. were studied by a microtiter broth dilution method. The MIC 90 s for M. abscessus, M. fortuitum, and Nocardia spp. were 0.5 g/ml, 0.03 g/ml, and 8 g/ml, respectively. TP-271 was significantly more active than the respective control drug in virtually all tests. Mycobacterium abscessus and Mycobacterium fortuitum are rapidly growing mycobacteria that are associated primarily with opportunistic infections in immunocompromised subjects (2). Patients with bronchiectasis, especially those with cystic fibrosis, are at increased risk of M. abscessus infection. Other manifestations of M. abscessus infection include localized skin infections, postoperative wound infections, and infection of implanted medical devices. M. fortuitum is a relatively rare pathogen, even in immunocompromised individuals, but has been associated with skin infections and hospital-acquired postoperative infections (2). The most common clinical form of Nocardia infection is pulmonary nocardiosis, with and without dissemination, followed by skin and soft tissue infection (5).Infections due to these microorganisms are occurring with increasing frequency and are often difficult to treat, especially the mycobacterial infections. Successful treatment is often hindered by the need for combination therapy, resistance to multiple drugs, necessity of long treatment duration, and lack of sufficiently active oral drugs (2, 3, 6).While Nocardia remains susceptible to trimethoprim-sulfamethoxazole in the majority of cases, effective alternative oral therapy is lacking. Mortality from pulmonary nocardiosis remains high, in the range of 15 to 40% (5, 11).TP-271 is a novel, fully synthetic fluorocycline antimicrobial related to tetracycline ( Fig. 1) (1, 10). It has been shown to have potent broad-spectrum in vitro and in vivo activity against multiple community-acquired organisms, including Staphylococcus spp., Streptococcus spp., Haemophilus influenzae, Moraxella catarrhalis, Legionella pneumophila, and Acinetobacter baumannii, as well as biothreat organisms (Bacillus anthracis, Francisella tularensis, Burkholderia pseudomallei, and Burkholderia mallei) (4). The activity of TP-271 was shown to be unaffected by the Gram-positive tetracycline-specific pump tet(K) and ribosomal protection mechanism tet(M) and minimally affected by the most common Gram-negative efflux mechanisms, tet(A) and tet(B) (7). Promising oral activity was demonstrated by TP-271 in neutropenic mouse models of pneumonia caused by methicillin-resistant Staphylococcus aureus and Streptococcus pneumoniae and in immunocompetent models of pneumonia caused by S. pneumoniae in mice and H. influenzae in rats (4).As a first step in its assessment as a novel therapy to treat infections caused by M. abscessus, M. fortuitum, and Nocardia spp., we evaluated the in vitro activity of TP-271 in comparison to those of se...

Background In hospitalized people with HIV (PWH) there is an increased risk of mortality from COVID-19 among hospitalized PWH as compared to HIV-negative individuals. Evidence suggests that tocilizumab—a humanized monoclonal interleukin (IL)-6 receptor inhibitor (IL-6ri) antibody—has a modest mortality benefit when combined with corticosteroids in select hospitalized COVID-19 patients who are severely ill. Data on clinical outcomes after tocilizumab use in PWH with severe COVID-19 are lacking. Case presentation We present a multinational case series of 18 PWH with COVID-19 who were treated with IL-6ri’s during the period from April to June 2020. Four patients received tocilizumab, six sarilumab, and eight received an undocumented IL-6ri. Of the 18 patients in the series, 4 (22%) had CD4 counts < 200 cells/mm3; 14 (82%) had a suppressed HIV viral load. Eight patients (44%), all admitted to ICU, were treated for secondary infection; 5 had a confirmed organism. Of the four patients with CD4 counts < 200 cells/mm3, three were treated for secondary infection, with 2 confirmed organisms. Overall outcomes were poor—12 patients (67%) were admitted to the ICU, 11 (61%) required mechanical ventilation, and 7 (39%) died. Conclusions In this case series of hospitalized PWH with COVID-19 and given IL-6ri prior to the common use of corticosteroids, there are reports of secondary or co-infection in severely ill patients. Comprehensive studies in PWH, particularly with CD4 counts < 200 cells, are warranted to assess infectious and other outcomes after IL-6ri use, particularly in the context of co-administered corticosteroids.

Background Raoultella ornitholytica (R. ornitholytica) is a waterborne Gram-negative bacilli increasingly found in hospitals. Multi-drug resistance has been reported, including to carbapenems. Our objective was to identify demographics of R. ornitholytica at Danville Regional Medical Center (DRMC) to determine predisposing factors to infection and potential antibiotic resistance.MethodsCultures positive for R. ornitholytica were identified through DRMC’s electronic medical records (EMR) from 1/2010 to 3/2017. Site of infection, concurrent infections, isolate susceptibilities, prior antibiotic exposure, and appropriateness of treatment were extracted from the EMR. Healthcare associated was defined as occurring in the hospital, nursing home, long-term acute care, or inpatient rehabilitation facility within the past 90 days. Those with diabetes, cancer, and end stage renal disease (ESRD) were qualified as immunosuppressed.ResultsThirty-two cases were isolated, of which 20 had associated clinical data. One urine isolate was consistent with colonization. Of the 19 infections, the majority (n = 15) were urinary tract infections (UTIs) and one case each from bronchial washing, heel wound, blood culture, and vulvar lesion. Clinical demographics are shown in Figure 1. Thirteen (65%) had concurrent infections, of which 5 (26%) were co-infected with Enterococcus faecalis, one which was vancomycin resistant. Three had chronic Foley catheters, constituting 20% of the UTIs. Susceptibilities are reported in Figure 2. Prior antibiotic use is shown in Figure 3.ConclusionMost of the isolates from our institution were relatively sensitive, with most resistance to ampicillin. Two isolates were pansensitive, however one case was sensitive only to nitrofurantoin and ertapenem. All isolates which were resistant to cefazolin and ceftriaxone had prior exposure. The elderly and diabetics had the greatest association with infection. A majority of patients had a concurrent infection, which may suggest this as an opportunistic organism. Our findings warrant further studies to better characterize clinical associations and development of resistance in response to prior antibiotic exposure.Disclosures All authors: No reported disclosures.