In Vitro and In Vivo Activity of Amoxicillin-Clavulanate Combined with Ceftibuten or Cefpodoxime Against Extended-Spectrum ß-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae.

Infections due to extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales are an increasingly common problem. For many of these infections, no oral treatment options are available. The activity of amoxicillin-clavulanate combined with ceftibuten or cefpodoxime was evaluated against a group of Escherichia coli and Klebsiella pneumoniae clinical isolates possessing a variety of CTX-M- and SHV-type ESBLs; some possessed blaTEM1 as well. In time-kill studies, the combination of subinhibitory concentrations of amoxicillin-clavulanate with ceftibuten was bactericidal and synergistic for all strains with an amoxicillin-clavulanate MIC ≤32 µg/mL, regardless of the type of ESBL and the cephalosporin minimal inhibitory concentration (MIC). The combination with cefpodoxime was also bactericidal and synergistic against all but one of these strains. These combinations were further tested against two strains of K. pneumoniae and one E. coli in a sepsis model using Galleria mellonella larvae. The combination of amoxicillin-clavulanate with ceftibuten demonstrated a synergistic survival benefit against all three strains. The combination with cefpodoxime also improved survival against the two K. pneumoniae strains, but not the E. coli strain. These findings support combining amoxicillin-clavulanate with ceftibuten, and possibly cefpodoxime, for the treatment of infections due to ESBL producers and suggest that having an amoxicillin-clavulanate MIC of 32 µg/mL or less may predict activity at clinically achievable concentrations. Clinical studies are warranted to further evaluate this therapeutic approach.

Relationship of TonB-dependent receptors with susceptibility to cefiderocol in clinical isolates of Pseudomonas aeruginosa.

OBJECTIVES: Cefiderocol maintains activity against most MDR Gram-negative pathogens including Pseudomonas aeruginosa. In laboratory-derived isolates, down-regulation of TonB-dependent siderophore receptors have been implicated in resistance to cefiderocol. METHODS: In this report, the expression of seven TonB-dependent siderophore receptors was examined in 10 clinical isolates with cefiderocol MICs ranging from ≤0.03-8 mg/L. In addition, genetic sequences of the siderophore receptors were analysed to identify potentially disruptive mutations. RESULTS: There was no clear association between expression of the receptors with cefiderocol susceptibility, including the receptors piuA/piuD and pirA previously implicated in cefiderocol uptake. In addition, there were no disabling mutations identified in the receptors. Acquired ß-lactamase activity also could not explain the range in cefiderocol susceptibility. CONCLUSIONS: The aetiology of reduced susceptibility to cefiderocol in clinical isolates of P. aeruginosa remains an enigma and worthy of further investigation.

Trends in Healthcare Facility-Onset Clostridioides difficile Infection and the Impact of Testing Schemes in an Acute Care Hospital System in New York City, 2016-2019.

BACKGROUND: Healthcare facility-onset Clostridioides difficile infection is associated with adverse clinical outcomes and hospital reimbursement. A four-year review involving eleven hospitals of the NYC Health + Hospital system was undertaken. METHODS: From 2016-2019, infection rates and standardized infection ratios (SIRs) were gathered from National Healthcare Safety Network. The C. difficile testing scheme at each facility was recorded. RESULTS: For the eleven hospitals, declines in rates of C. difficile infection and SIRs were documented. However, this decline was driven by two hospitals that had high rates of infection in 2016; for the remaining nine hospitals, rates of infection and SIRs were at a plateau. Most hospitals used a testing scheme that fell into the nucleic acid amplification test (NAAT) category for SIR risk adjustment. Hospitals that used the algorithm glutamate dehydrogenase (GDH) and toxin A/B immunoassay (EIA) followed by NAAT for discrepant results had significantly lower rates of C. difficile infection but similar SIRs. CONCLUSIONS: For most hospitals in this system, rates of C. difficile remained level. Within the NAAT test categories, SIRs may not correlate with infection rates. Given the controversies regarding testing and calculation of SIRs, alternatives to C. difficile infection should be sought as a hospital quality measurement.

Trends in central-line-associated bloodstream infections and catheter-associated urinary tract infections in a large acute-care hospital system in New York City, 2016-2019.

BACKGROUND: Central-line bloodstream infections (CLABSIs) and catheter-associated urinary tract infections (CAUTIs) negatively impact clinical outcomes and hospital reimbursement. In this report, 4 year trends involving 11 hospitals in New York City were examined. METHODS: Data from the National Healthcare Safety Network (NHSN) were extracted for 11 acute-care hospitals belonging to the NYC Health + Hospital system from 2016 through 2019. Trends in device infections per 1,000 patient days, device utilization ratios, and standardized infection ratios (SIRs) were examined for the 11 hospitals and for the entire system. RESULTS: Over the 4-year period, there were progressive declines in central-line days, infections per 1,000 central-line days, and device utilization ratios for the system. The average annual SIRs for the system also declined: 1.40 in 2016, 1.09 in 2017, 1.04 in 2018, and 0.82 in 2019. Case-mix indices correlated with SIRs for CLABSIs. Level 1 trauma centers had higher SIRs and a disproportionately greater number of CLABSIs in patients located in NHSN-defined surgical intensive care units. Similar trends with CAUTIs were noted, with progressive declines in catheter days, infections per 1,000 patient days, device utilization ratios, and SIRs (1.42 in 2016, 0.93 in 2017, 1.18 in 2018, and 0.78 in 2019) over the 4-year period. CONCLUSIONS: Across an 11-hospital system, continuing efforts to reduce device utilization and infection rates resulted in declining SIRs for CLABSIs and CAUTIs. Hospitals with higher case-mix indices, and particularly level 1 trauma centers, had significantly higher central-line infection rates and SIRs.

Activity of Omadacycline and Other Tetracyclines Against Contemporary Gram-Negative Pathogens from New York City Hospitals.

Antibiotic-resistant Enterobacteriaceae and Acinetobacter baumannii are problematic pathogens, with few treatment options for multidrug-resistant (MDR)-A. baumannii and few oral options for extended spectrum ß-lactamase (ESBL)-producing and MDR-Enterobacteriaceae. Omadacycline, a newer tetracycline derivative, has activity against some of these pathogens. We tested the in vitro activity of omadacycline against a contemporary collection of over 2,600 consecutive unique clinical isolates of Enterobacteriaceae and A. baumannii, a previous collection of carbapenem-resistant Klebsiella pneumoniae and A. baumannii from a surveillance study in 2013-2014, and a group of K. pneumoniae and A. baumannii isolates with previously defined resistance mechanisms. For the contemporary collection, over 96% of Escherichia coli and 70% of K. pneumoniae isolates were inhibited by omadacycline at ≤4 µg/mL including 95% of E. coli and 49% of K. pneumoniae with presumptive ESBLs. Nearly 90% of A. baumannii were inhibited by omadacycline at ≤4 µg/mL. The omadacycline MIC50/90 was 1/4 µg/mL, 4/>8 µg/mL, and 0.5/8 for E. coli, K. pneumoniae, and A. baumannii, respectively. For the carbapenem-resistant collection of isolates, 56% of A. baumannii were inhibited by omadacycline at ≤4 µg/mL, but only 30% of Klebsiella pneumoniae carbapenemase (KPC)-possessing K. pneumoniae were susceptible. Expression of the efflux gene adeB appeared to affect the activity of omadacycline against A. baumannii, but could not fully explain resistance to this agent. Omadacycline may prove to be a parenteral or oral option for some infections due to ESBL-producing Enterobacteriaceae and carbapenem-resistant A. baumannii, and clinical studies are warranted.

Cefiderocol Resistance in Acinetobacter baumannii: Roles of ß-Lactamases, Siderophore Receptors, and Penicillin Binding Protein 3.

Cefiderocol is a siderophore cephalosporin active against many multidrug-resistant (MDR) Gram-negative pathogens. We examined the resistance mechanisms in 12 Acinetobacter baumannii strains with cefiderocol MICs ranging from ≤0.03 to >32 µg/ml. Cefiderocol resistance could not be explained by ß-lactamase activity. Cefiderocol resistance was associated with reduced expression of the siderophore receptor gene pirA Mutations involving PBP3 may have contributed to resistance in one strain. Additional studies are needed to assess the role of other siderophore receptors.

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.

In Vitro and In Vivo Activity of a Novel Antisense Peptide Nucleic Acid Compound Against Multidrug-Resistant Acinetobacter baumannii.

Multidrug-resistant (MDR) Acinetobacter baumannii is a difficult pathogen due to its propensity to develop resistance to antibiotics. Antisense nucleic acid analogs have been proposed as a potential alternative anti-infective approach. We developed a peptide nucleic acid (PNA) compound that targets the essential Acinetobacter gene carA. The PNA oligomer was conjugated to the cell-penetrating peptide (RXR)4XB. In vitro testing of the PNA conjugate against four clinical strains of MDR-A. baumannii in minimal medium demonstrated that all four strains were inhibited at a concentration of 1.25 µM. In vivo testing of the PNA conjugate was done using a Galleria mellonella model of sepsis caused by one of the clinical strains. Preliminary testing of a variety of inocula demonstrated that an inoculum of 1 × 106 cfu was lethal to the majority of caterpillars by day 3, but not within 24 hours. The PNA compound was administered 30 minutes after an inoculum of 1 × 106 cfu at doses estimated to produce concentrations of ∼5 and 20 µM. The PNA compound had no effect at the lower dose. However, the higher dose reduced mortality from 5/28 (18%) to 0/28 (0%) at day 1 (p = 0.051) and from 19/28 (68%) to 9/28 (32%) at day 6 (p = 0.015). Antisense therapy is a novel approach to dealing with difficult MDR pathogens that could circumvent the problem of progressive resistance to available antibiotics. Further studies need to be done with additional strains and more complex in vivo model systems.

Carbapenemases in New York City: the continued decline of KPC-producing Klebsiella pneumoniae, but a new threat emerges.

Objectives: Carbapenemase-producing Enterobacteriaceae are important nosocomial pathogens in many medical centres. Surveillance is needed to track trends and detect emergence of new carbapenemases. Methods: Single-patient isolates of Enterobacteriaceae were gathered from seven medical centres in New York City over a 3 month period in 2017. Susceptibility testing was performed and isolates were screened for selected carbapenemases. Additional isolates referred to our laboratory in 2018 were also tested. Results: KPC was found in 3/1911 (0.16%) isolates of Escherichia coli, 22/533 (4.1%) isolates of Klebsiella pneumoniae and 3/175 (1.7%) isolates of Enterobacter spp. Compared with prior surveillance studies performed over the past decade, there has been a persistent decline in the number of KPC-possessing K. pneumoniae. However, in 2018 two patients from the same skilled nursing facility admitted to two separate hospitals were found to harbour Enterobacteriaceae with NDM-5 and CTX-M-15. Conclusions: Since the height of the outbreak in 2006, there has been a decline in the number of KPC-possessing Enterobacteriaceae in New York City acute care medical centres. However continued vigilance is needed to detect the emergence of other carbapenemases.

Effect of Porins and blaKPC Expression on Activity of Imipenem with Relebactam in Klebsiella pneumoniae: Can Antibiotic Combinations Overcome Resistance?

Imipenem with relebactam is a novel ß-lactam-ß-lactamase inhibitor that has activity against most KPC-producing Enterobacteriaceae. Using 10 isolates of KPC-possessing Klebsiella pneumoniae, we assessed the relationship between imipenem-relebactam minimum inhibitory concentrations (MICs) and mechanisms known to contribute to antimicrobial resistance. The effect of adding a second agent was assessed by time-kill experiments. Mutations affecting the genes encoding porins ompK35 and ompK36 and identification of ß-lactamases were assessed by PCR. Expression of blaKPC and acrB was assessed by real-time reverse-transcriptase (RT)-PCR, and production of OmpK36 by SDS-PAGE. Time-kill studies were performed using combinations of imipenem-relebactam with polymyxin B, amikacin, or tigecycline. Seven isolates having a disruption in a single porin, or in neither porin, remained susceptible to imipenem-relebactam. The addition of a second agent did not improve the activity of imipenem-relebactam for these isolates, although the addition of tigecycline was antagonistic for three isolates. Three isolates had major disruptions in both ompK35 and ompK36 that correlated with reduced activity of imipenem-relebactam (MICs 2/4, 8/4, and 512/4 µg/mL). Two of these isolates also had overexpression of blaKPC, including the isolate with the highest MIC. These isolates were also resistant to polymyxin B and amikacin. The addition of amikacin provided both synergistic and bactericidal activity for the two more resistant isolates. The activity of imipenem-relebactam against K. pneumoniae is affected by major disruptions of both ompK35 and ompK36 and by expression of the KPC gene. Combining imipenem-relebactam with an aminoglycoside may be a promising approach for isolates with reduced susceptibility to imipenem-relebactam.

In vitro and in vivo activity of single and dual antimicrobial agents against KPC-producing Klebsiella pneumoniae.

Objectives: Options for treatment of infections due to KPC-producing Klebsiella pneumoniae are limited and combination therapy is often recommended. In this report, the in vitro and in vivo activity of potential therapeutic agents and combinations was assessed against four KPC-producing K. pneumoniae isolates. Methods: Using clinically relevant concentrations, time-kill experiments and the Galleria mellonella model of infection were used to examine the activity of polymyxin B, ceftazidime/avibactam, meropenem, rifampicin and amikacin alone and in combination. Results: Two K. pneumoniae isolates were resistant to polymyxin B and had ceftazidime/avibactam MICs of 8/4 mg/L. When ceftazidime/avibactam was combined with either amikacin or meropenem, synergy was observed in vitro, and these combinations were associated with improved survival in the in vivo model. Improved survival was also observed using higher doses of ceftazidime/avibactam. The other two K. pneumoniae isolates were susceptible to polymyxin B and had lower (1/4 mg/L) MICs of ceftazidime/avibactam. For these two isolates, bactericidal activity was observed in vitro at ceftazidime/avibactam concentrations four times the MIC. At one-quarter of the MIC, synergy was observed when ceftazidime/avibactam was combined with meropenem. In the in vivo model with the two susceptible isolates, improved survival rates were observed following therapy with ceftazidime/avibactam monotherapy. For all four isolates, polymyxin B with or without rifampicin or meropenem performed poorly in the in vivo model. Conclusions: Pending clinical studies, combining ceftazidime/avibactam with another agent (e.g. a carbapenem) should be considered when treating serious infections due to these pathogens, particularly for isolates with ceftazidime/avibactam MICs near the susceptibility breakpoint.

Activity of Ceftazidime-Avibactam Against Clinical Isolates of Klebsiella pneumoniae, Including KPC-Carrying Isolates, Endemic to New York City.

In this report, we examined the (1) activity of ceftazidime-avibactam against clinical isolates Klebsiella pneumoniae, including those harboring blaKPC, (2) potential mechanisms leading to reduced susceptibility, and (3) activity of ceftazidime-avibactam when combined with other agents. Of 802 carbapenem-resistant isolates of K. pneumoniae gathered from New York City from 1999 to 2014, all were susceptible to ceftazidime-avibactam. Minimum inhibitory concentrations (MICs) were higher in isolates with K. pneumoniae, with the carbapenemase (KPC)-3 (compared to KPC-2), and those with a frameshift mutation in ompK35. MICs did not appear to be affected by changes in ompK36 or by expression of acrB. Time-kill experiments demonstrated synergy between either polymyxin B or amikacin and ceftazidime-avibactam in a minority of isolates. In conclusion, ceftazidime-avibactam is active against K. pneumoniae, including blaKPC isolates, in our region, but activity is affected by KPC subtype and by mutations in ompK35. Synergy can occur when combined with polymyxin B or amikacin, but is unpredictable.

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 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.

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.

Reduction in the prevalence of carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa in New York City.

We compared susceptibilities of Acinetobacter baumannii and Pseudomonas aeruginosa collected during surveillance studies conducted during 2009 and 2013-2014 involving hospitals in New York City. There were significant decreases in the number of carbapenem-resistant A baumannii and P aeruginosa cases during 2013-2014; it appears the institution of effective infection control measures has contributed to this decline. However the number of isolates of A baumannii with OXA-23-type ß-lactamase increased during 2013-2014.