Early Introduction and Community Transmission of SARS-CoV-2 Omicron Variant, New York, New York, USA.

The Omicron variant of SARS-CoV-2 has become dominant in most countries and has raised significant global health concerns. As a global commerce center, New York, New York, USA, constantly faces the risk for multiple variant introductions of SARS-CoV-2. To elucidate the introduction and transmission of the Omicron variant in the city of New York, we created a comprehensive genomic and epidemiologic analysis of 392 Omicron virus specimens collected during November 25-December 11, 2021. We found evidence of 4 independent introductions of Omicron subclades, including the Omicron subclade BA.1.1 with defining substitution of R346K in the spike protein. The continuous genetic divergence within each Omicron subclade revealed their local community transmission and co-circulation in New York, including both household and workplace transmissions supported by epidemiologic evidence. Our study highlights the urgent need for enhanced genomic surveillance and effective response planning for better prevention and management of emerging SARS-CoV-2 variants.

Rise and fall of KPC-producing Klebsiella pneumoniae in New York City.

OBJECTIVES: The study objective was to examine the epidemiological trends of KPC-producing Klebsiella pneumoniae in New York City medical centres. PATIENTS AND METHODS: Single patient isolates of K. pneumoniae were collected from nine medical centres in New York City during a 3 month period from 2013 to 2014. Isolates were tested for the presence of blaKPC. Results were compared with similar surveillance studies conducted in 2006 and 2009. Infection control data, including utilization of medical devices, were analysed at a subset of hospitals. RESULTS: There was a progressive decline in the percentage of K. pneumoniae harbouring blaKPC from 2006 to 2013-14. For the nine hospitals that participated in all three surveillance studies, the percentages of isolates with blaKPC fell from 36% in 2006 to 25% in 2009 to 13% in 2013-14. Seven of the nine hospitals had marked declines in isolates with blaKPC, while two hospitals continued to struggle with this pathogen. These two hospitals were smaller and had longer lengths of patient stay. Device utilization rates were obtained from two hospitals that successfully controlled the spread of KPC-producing K. pneumoniae; both had ∼20%-25% reduction in the usage of urinary catheters. Changes in antibiotic usage at one hospital could not explain the decline in these pathogens. CONCLUSIONS: Over the past decade there has been a steady decline in KPC-producing K. pneumoniae in most New York City hospitals. The reason for the decline is probably multifactorial, involving a reduction in device (catheter) utilization and possibly an improvement in infection control practices.

Activity of eravacycline against Enterobacteriaceae and Acinetobacter baumannii, including multidrug-resistant isolates, from New York City.

Eravacycline demonstrated in vitro activity against a contemporary collection of more than 4,000 Gram-negative pathogens from New York City hospitals, with MIC50/MIC90 values, respectively, for Escherichia coli of 0.12/0.5 µg/ml, Klebsiella pneumoniae of 0.25/1 µg/ml, Enterobacter aerogenes of 0.25/1 µg/ml, Enterobacter cloacae 0.5/1 µg/ml, and Acinetobacter baumannii of 0.5/1 µg/ml. Activity was retained against multidrug-resistant isolates, including those expressing KPC and OXA carbapenemases. For A. baumannii, eravacycline MICs correlated with increased expression of the adeB gene.

Activity of Imipenem with Relebactam against Gram-Negative Pathogens from New York City.

Imipenem with relebactam was active against Escherichia coli, Klebsiella pneumoniae, and Enterobacter spp., including K. pneumoniae carbapenemase (KPC)-producing isolates. Loss of OmpK36 in KPC-producing K. pneumoniae isolates affected the susceptibility of this combination. Enhanced activity was evident against Pseudomonas aeruginosa, including isolates with depressed oprD and increased ampC expression. However, the addition of relebactam to imipenem did not provide added benefit against Acinetobacter baumannii. The combination of imipenem with relebactam demonstrated activity against KPC-producing Enterobacteriaceae and multidrug-resistant P. aeruginosa.

Activity of Meropenem Combined with RPX7009, a Novel ß-Lactamase Inhibitor, against Gram-Negative Clinical Isolates in New York City.

Multidrug-resistant Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae are endemic to hospitals in New York City and other regions. RPX7009 is a novel ß-lactamase inhibitor with activity against serine carbapenemases. We tested the activity of meropenem plus RPX7009 against 4,500 recent Gram-negative clinical isolates from 11 New York City hospitals. The meropenem-RPX7009 combination was found to have excellent in vitro activity against Escherichia coli, K. pneumoniae, and Enterobacter spp., including multidrug-resistant (MDR) KPC-producing strains. Overall, 131/133 (98.5%) KPC-producing Enterobacteriaceae strains were inhibited by meropenem (≤1 µg/ml) plus RPX7009 (8 µg/ml). In a limited number of strains, the combination appeared to have reduced activity against KPC-producing K. pneumoniae isolates with diminished ompK35 and ompK36 expression. The addition of RPX7009 did not affect the activity of meropenem against Acinetobacter baumannii and Pseudomonas aeruginosa. The meropenem-RPX7009 combination shows promise as a novel agent against KPC-producing Enterobacteriaceae and deserves further study. Other approaches will be needed to address multidrug-resistant A. baumannii and P. aeruginosa, which typically possess different mechanisms of carbapenem resistance.

Evaluation of Remel Spectra CRE Agar for Detection of Carbapenem-Resistant Bacteria from Rectal Swabs Obtained from Residents of a Long-Term-Care Facility.

We compared the Remel Spectra CRE agar plate to CDC standard methodology for the isolation of carbapenem-resistant Enterobacteriaceae (CRE) from 300 rectal swab specimens obtained from patients residing in a long-term-care facility (LTCF). Multiplex PCR experiments were performed on isolates to identify specific Klebsiella pneumoniae carbapenemases (KPC) and additional ß-lactamases. Of the 300 patients, 72 (24%) harbored CRE and were PCR positive for KPC enzymes. The Remel Spectra CRE plates detected KPC-type CRE in isolates from 70 of 72 patients (97.2%), while the CDC method detected CRE in 56 of 72 (77.8%). CRE identification results were available in 18 h compared to 36 h for the CDC method. Remel Spectra CRE agar plates can provide useful means for a fast and reliable method for detecting KPC-type CRE and for accelerated institution of appropriate infection control precautions.

Abrupt emergence of a single dominant multidrug-resistant strain of Escherichia coli.

BACKGROUND: Fluoroquinolone-resistant Escherichia coli are increasingly prevalent. Their clonal origins--potentially critical for control efforts--remain undefined. METHODS: Antimicrobial resistance profiles and fine clonal structure were determined for 236 diverse-source historical (1967-2009) E. coli isolates representing sequence type ST131 and 853 recent (2010-2011) consecutive E. coli isolates from 5 clinical laboratories in Seattle, Washington, and Minneapolis, Minnesota. Clonal structure was resolved based on fimH sequence (fimbrial adhesin gene: H subclone assignments), multilocus sequence typing, gyrA and parC sequence (fluoroquinolone resistance-determining loci), and pulsed-field gel electrophoresis. RESULTS: Of the recent fluoroquinolone-resistant clinical isolates, 52% represented a single ST131 subclonal lineage, H30, which expanded abruptly after 2000. This subclone had a unique and conserved gyrA/parC allele combination, supporting its tight clonality. Unlike other ST131 subclones, H30 was significantly associated with fluoroquinolone resistance and was the most prevalent subclone among current E. coli clinical isolates, overall (10.4%) and within every resistance category (11%-52%). CONCLUSIONS: Most current fluoroquinolone-resistant E. coli clinical isolates, and the largest share of multidrug-resistant isolates, represent a highly clonal subgroup that likely originated from a single rapidly expanded and disseminated ST131 strain. Focused attention to this strain will be required to control the fluoroquinolone and multidrug-resistant E. coli epidemic.

KPC presence in Pseudomonas aeruginosa has minimal impact on the in vivo efficacy of carbapenem therapy.

While reports of Klebsiella pneumoniae carbapenemase (KPC) production among Pseudomonas aeruginosa strains have emerged from a number of countries worldwide, outcome data are lacking. This is the first report evaluating how KPC production in P. aeruginosa impacts the efficacy of carbapenems by using the murine thigh infection model. Our findings suggest that the impact of KPC-2 in vivo is less pronounced than would be anticipated based on the in vitro potency.

Identification of extended-spectrum-ß-lactamase-positive Klebsiella pneumoniae urinary tract isolates harboring KPC and CTX-M ß-lactamases in nonhospitalized patients.

Forty-seven extended-spectrum-ß-lactamase-positive Klebsiella pneumoniae urinary tract isolates from nonhospitalized patients were identified, and 79% harbored KPC and/or CTX-M ß-lactamases. Approximately 90% of the isolates were resistant to trimethoprim-sulfamethoxazole and levofloxacin, and 40% were resistant to a carbapenem, while 92% were susceptible to polymyxin B, 87% were susceptible to tigecycline, and 79% were susceptible to fosfomycin. Increased use of broader-spectrum antibiotics may help to prevent their dissemination and reduce the risk of progression to invasive disease.

Efficacy of doripenem and ertapenem against KPC-2-producing and non-KPC-producing Klebsiella pneumoniae with similar MICs.

OBJECTIVES: In the clinical setting, the choice of definitive drug therapy is typically guided by the antimicrobial susceptibility profile of the infecting organism. We evaluated the activity of doripenem and ertapenem against Klebsiella pneumoniae isolates with similar MICs that exhibited KPC-based and non-KPC-based genotypes. METHODS: Five doripenem-non-susceptible K. pneumoniae isolates, three producing KPC carbapenemases and two exhibiting porin modifications plus AmpC ß-lactamase production, were tested in a neutropenic murine thigh infection model. The ertapenem MIC for all isolates was >32 mg/L. Regimens of 2 g of doripenem every 8 h (4 h infusion) and 1 g of ertapenem every 24 h (0.5 h infusion) simulating human concentration-time profiles were administered 2 h after inoculation. The change in bacterial density was evaluated after 24 h of therapy. RESULTS: Consistent with the observed MICs, treatment with ertapenem resulted in minimal activity against all isolates tested. When comparing the activity of doripenem between the KPC and non-KPC producers with doripenem MICs of 8 mg/L, significantly better activity was noted for the non-KPC producer (P<0.001). Likewise, when comparing the two KPC-producing isolates with doripenem MICs of 24 mg/L and >32 mg/L with the non-KPC producer with an MIC of 32 mg/L, significantly greater activity was noted for the non-KPC producer (P<0.001). CONCLUSIONS: When doripenem MICs were similar, activity was greater for non-KPC-producing isolates when compared with KPC producers. While the in vitro MIC is typically the sole method utilized to aid in drug selection, these data suggest that the genetic driver behind these MICs may also play a role in predicting in vivo activity.

Omadacycline for the treatment of Mycobacterium abscessus infections: Case series and review of the literature.

Treatment of Mycobacterium abscessus infections are problematic due to inherent multidrug resistance and lack of response to antibacterials commonly used as therapy for other mycobacterial infections. We report the clinical success of five patients who received definitive-treatment with an omadacycline-containing combination regimen for M. abscessus infection.

A case of Lactobacillus jensenii associated native valve endocarditis.

Lactobacillus jensenii is rarely reported as a cause of endocarditis in immunocompetent patients. We describe a case of Lactobacillus jensenii associated native valve endocarditis that was identified using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) technology. While most Lactobacillus species are generally resistant to vancomycin, Lactobacillus jensenii is frequently susceptible, but treatment requires accurate susceptibility results followed by timely medical and surgical intervention. Probiotic use in patients can be a risk factor for infection with Lactobacillus species.

Comparison of Escherichia coli ST131 pulsotypes, by epidemiologic traits, 1967-2009.

Escherichia coli sequence type 131 (ST131), an emerging disseminated public health threat, causes multidrug-resistant extraintestinal infections. Among 579 diverse E. coli ST131 isolates from 1967-2009, we compared pulsotypes (>94% similar XbaI pulsed-field gel electrophoresis profiles) by collection year, geographic origin, source, and antimicrobial drug-resistance traits. Of 170 pulsotypes, 65 had >2 isolates and accounted for 85% of isolates. Although extensively dispersed geographically, pulsotypes were significantly source specific (e.g., had little commonality between humans vs. foods and food animals). The most prevalent pulsotypes were associated with recent isolation, humans, and antimicrobial drug resistance. Predominant pulsotype 968 was associated specifically with fluoroquinolone resistance but not with extended-spectrum ß-lactamase production or bla(CTX-M-15). Thus, several highly successful antimicrobial drug-resistant lineages within E. coli ST131 have recently emerged and diffused extensively among locales while maintaining a comparatively restricted host/source range. Identification of factors contributing to this behavior of ST131 could help protect public health.

Molecular epidemiological analysis of Escherichia coli sequence type ST131 (O25:H4) and blaCTX-M-15 among extended-spectrum-ß-lactamase-producing E. coli from the United States, 2000 to 2009.

Escherichia coli sequence type ST131 (from phylogenetic group B2), often carrying the extended-spectrum-ß-lactamase (ESBL) gene bla(CTX-M-15), is an emerging globally disseminated pathogen that has received comparatively little attention in the United States. Accordingly, a convenience sample of 351 ESBL-producing E. coli isolates from 15 U.S. centers (collected in 2000 to 2009) underwent PCR-based phylotyping and detection of ST131 and bla(CTX-M-15). A total of 200 isolates, comprising 4 groups of 50 isolates each that were (i) bla(CTX-M-15) negative non-ST131, (ii) bla(CTX-M-15) positive non-ST131, (iii) bla(CTX-M-15) negative ST131, or (iv) bla(CTX-M-15) positive ST131, also underwent virulence genotyping, antimicrobial susceptibility testing, and pulsed-field gel electrophoresis (PFGE). Overall, 201 (57%) isolates exhibited bla(CTX-M-15), whereas 165 (47%) were ST131. ST131 accounted for 56% of bla(CTX-M-15)-positive- versus 35% of bla(CTX-M-15)-negative isolates (P < 0.001). Whereas ST131 accounted for 94% of the 175 total group B2 isolates, non-ST131 isolates were phylogenetically distributed by bla(CTX-M-15) status, with groups A (bla(CTX-M-15)-positive isolates) and D (bla(CTX-M-15)-negative isolates) predominating. Both bla(CTX-M-15) and ST131 occurred at all participating centers, were recovered from children and adults, increased significantly in prevalence post-2003, and were associated with molecularly inferred virulence. Compared with non-ST131 isolates, ST131 isolates had higher virulence scores, distinctive virulence profiles, and more-homogeneous PFGE profiles. bla(CTX-M-15) was associated with extensive antimicrobial resistance and ST131 with fluoroquinolone resistance. Thus, E. coli ST131 and bla(CTX-M-15) are emergent, widely distributed, and predominant among ESBL-positive E. coli strains in the United States, among children and adults alike. Enhanced virulence and antimicrobial resistance have likely promoted the epidemiological success of these emerging public health threats.

Fatal case of disseminated cryptococcal infection and meningoencephalitis in the setting of prolonged glucocorticoid use in a Covid-19 positive patient.

Based on the RECOVERY trial, glucocorticoids have become the mainstay of treatment for COVID-19, thus increasing the risk of opportunistic infections. We report a case of disseminated Cryptococcus neoformans with documented meningoencephalitis in a patient with severe COVID-19 in the setting of prolonged glucocorticoid administration with poor outcome likely due to adrenal involvement.

Combination antibiotic therapy for treatment of a patient with infected prosthesis and peri-prosthetic abscess due to Klebsiella pneumoniae harboring New Delhi Metallo (NDM) beta-lactamase.

Treatment options for patients infected with multi-drug resistant gram-negative bacteria harboring metallo-beta-lactamases (MBLs) requires precision therapy. We present the case of a 20 year-old male with a right distal femoral peri-prosthetic abscess with presumed infected hardware and osteomyelitis in whom four multi-drug resistant gram negative bacteria were isolated. The rapid identification of an MBL producing organism, novel combination of therapy, and prompt infection prevention enforcement and education led to appropriate treatment of our patient as well as prevention of spread of organisms during and after hospitalization. This case illustrated successful management of multiple challenges faced by patients infected and/or harboring extensively resistant bacteria.

Implementation of a Collaborated Antimicrobial Stewardship Program and Outpatient Parenteral Antimicrobial Therapy (OPAT) Unit-driven Monoclonal Antibody Therapy Program for COVID-19 at an NYC Hospital.

OBJECTIVES: This study aimed to assess the processes and clinical outcomes of a joint collaboration between Antimicrobial Stewardship Program (ASP) and the outpatient parenteral antimicrobial therapy (OPAT) unit for delivery of monoclonal antibody therapy for mild-to-moderate COVID-19. METHODS: We carried out a retrospective, interim analysis of our COVID-19 monoclonal antibody therapy program. Outcomes included clinical response, incidence of hospitalization, and adverse events. RESULTS: A total of 175 patients (casirivimab-imdevimab, n = 130; bamlanivimab, n = 45) were treated between December 2020 and March 1, 2021. The median time from symptom onset was 6 (IQR 4, 8) days at time of treatment. Of 135 patients available for follow-up, 71.9% and 85.9% of patients reported symptom improvement within 3 and 7 days of treatment, respectively. A total of 9 (6.7%) patients required COVID-19-related hospitalization for progression of symptoms, all within 14 days of treatment. A total of 7 (4%) patients experienced an infusion-related reaction. CONCLUSIONS: ASP-OPAT collaboration is a novel approach to implement an efficient and safe monoclonal antibody therapy program for the treatment of mild-to-moderate COVID-19.

Polymyxin-resistant clinical isolates of Escherichia coli.

A surveillance study to identify patients from the community with Escherichia coli resistant to broad-spectrum cephalosporins discovered two isolates that were also resistant to polymyxin B and colistin. One isolate from a patient in the community and a second from a patient who received multiple courses of polymyxin B also possessed a CTX-M-15 enzyme. Resistance to cationic peptides in E. coli is unusual, and testing for susceptibility to these agents should be performed.

Molecular epidemiology of carbapenem-nonsusceptible Acinetobacter baumannii in the United States.

Acinetobacter baumannii is emerging as an important nosocomial pathogen worldwide. We report molecular epidemiology of 65 carbapenem-nonsusceptible A. baumannii isolates identified from hospitals in New York, Pennsylvania, Florida, Missouri, Nevada, and California between 2008 and 2009. All isolates were subjected to pulsed-field gel electrophoresis (PFGE). Select isolates then underwent multilocus sequence typing (MLST). While the PFGE patterns tended to cluster within each hospital, sequence types (STs) belonging to the clonal complex 92 (CC92) and the pan-European clonal lineage II (EUII; worldwide clonal lineage 2) were predominant in all hospitals. Of them, ST122 and ST208 were the most common and were found in four of the six hospitals. Isolates belonging to the pan-European clonal lineages I and III were identified in one hospital each. Carbapenemase-encoding genes bla(OXA-23) and/or ISAba1-bla(OXA-51-like) were present among the majority of isolates. These findings suggest that carbapenem-nonsusceptible A. baumannii isolates found in U.S. hospitals constitute part of the global epidemic driven by CC92, but have unique STs other than ST92, which may be spreading by means of patient transfer between health care facilities within the United States.