Dalbavancin Sequential Therapy for Gram-Positive Bloodstream Infection: A Multicenter Observational Study.

INTRODUCTION: Long-acting lipoglycopeptides such as dalbavancin may have utility in patients with Gram-positive bloodstream infections (BSI), particularly in those with barriers to discharge or who require prolonged parenteral antibiotic courses. A retrospective cohort study was performed to provide further multicenter real-world evidence on dalbavancin use as a sequential therapy for Gram-positive BSI. METHODS: One hundred fifteen patients received dalbavancin with Gram-positive BSI, defined as any positive blood culture or diagnosed with infective endocarditis, from 13 centers geographically spread across the United States between July 2015 and July 2021. RESULTS: Patients had a mean (SD) age of 48.5 (17.5) years, the majority were male (54%), with many who injected drugs (40%). The most common infection sources (non-exclusive) were primary BSI (89%), skin and soft tissue infection (SSTI) (25%), infective endocarditis (19%), and bone and joint infection (17%). Staphylococcus aureus accounted for 72% of index cultures, coagulase-negative Staphylococcus accounted for 18%, and Streptococcus species in 16%. Dalbavancin started a median (Q1-Q3) of 10 (6-19) days after index culture collection. The most common regimen administered was dalbavancin 1500 mg as one dose for 50% of cases. The primary outcome of composite clinical failure occurred at 12.2%, with 90-day mortality at 7.0% and 90-day BSI recurrence at 3.5%. CONCLUSIONS: Dalbavancin may serve as a useful tool in facilitating hospital discharge in patients with Gram-positive BSI. Randomized controlled trials are anticipated to validate dalbavancin as a surrogate to current treatment standards.

Eravacycline, the first four years: health outcomes and tolerability data for 19 hospitals in 5 U.S. regions from 2018 to 2022.

IMPORTANCE: The rise of multidrug-resistant (MDR) pathogens, especially MDR Gram-negatives, poses a significant challenge to clinicians and public health. These resilient bacteria have rendered many traditional antibiotics ineffective, underscoring the urgency for innovative therapeutic solutions. Eravacycline, a broad-spectrum fluorocycline tetracycline antibiotic approved by the FDA in 2018, emerges as a promising candidate, exhibiting potential against a diverse array of MDR bacteria, including Gram-negative, Gram-positive, anaerobic strains, and Mycobacterium. However, comprehensive data on its real-world application remain scarce. This retrospective cohort study, one of the largest of its kind, delves into the utilization of eravacycline across various infectious conditions in the USA during its initial 4 years post-FDA approval. Through assessing clinical, microbiological, and tolerability outcomes, the research offers pivotal insights into eravacycline's efficacy in addressing the pressing global challenge of MDR bacterial infections.

Nephrotoxicity of Vancomycin in Combination With Beta-Lactam Agents: Ceftolozane-Tazobactam vs Piperacillin-Tazobactam.

BACKGROUND: Vancomycin (VAN)-associated acute kidney injury (AKI) is increased when VAN is combined with certain beta-lactams (BLs) such as piperacillin-tazobactam (TZP) but has not been evaluated with ceftolozane-tazobactam (C/T). Our aim was to investigate the AKI incidence of VAN in combination with C/T (VAN/C/T) compared with VAN in combination to TZP (VAN-TZP). METHODS: We conducted a multicenter, observational, comparative study across the United States. The primary analysis was a composite outcome of AKI and risk, injury, failure, loss, end stage renal disease; Acute Kidney Injury Network; or VAN-induced nephrotoxicity according to the consensus guidelines. Multivariable logistic regression analysis was conducted to adjust for confounding variables and stratified Kaplan-Meir analysis to assess the time to nephrotoxicity between the 2 groups. RESULTS: We included VAN/C/T (n = 90) and VAN-TZP (n = 284) at an enrollment ratio of 3:1. The primary outcome occurred in 12.2% vs 25.0% in the VAN-C/T and VAN-TZP groups, respectively (P = .011). After adjusting for confounding variables, VAN-TZP was associated with increased odds of AKI compared with VAN-C/T; with an adjusted odds ratio of 3.308 (95% confidence interval, 1.560-6.993). Results of the stratified Kaplan-Meir analysis with log-rank time-to-nephrotoxicity analysis indicate that time to AKI was significantly shorter among patients who received VAN-TZP (P = .004). Cox proportional hazards analysis demonstrated that TZP was consistent with the primary analysis (P = .001). CONCLUSIONS: Collectively, our results suggest that the AKI is not likely to be related to tazobactam but rather to piperacillin, which is a component in VAN-TZP but not in VAN-C/T.

Clinical Outcomes of Eravacycline in Patients Treated Predominately for Carbapenem-Resistant Acinetobacter baumannii.

Forty-six patients were treated with eravacycline (ERV) for Acinetobacter baumannii infections, where 69.5% of isolates were carbapenem resistant (CRAB). Infections were primarily pulmonary (58.3%), and most patients received combination therapy (84.4%). The median (IQR) ERV duration was 6.9 days (5.1 to 11.1). Thirty-day mortality was 23.9% in the cohort and 21.9% in CRAB patients. One patient experienced an ERV-possible adverse event. IMPORTANCE Acinetobacter baumannii, particularly when carbapenem resistant (CRAB), is one of the most challenging pathogens in the health care setting. This is complicated by the fact that there is no consensus guideline regarding management of A. baumannii infections. However, the recent Infectious Diseases Society of America guidelines for treatment of resistant Gram-negative infections provided expert recommendations for CRAB management. The panel suggest using minocycline among tetracycline derivatives rather than eravacycline (ERV) until sufficient clinical data are available. Therefore, we present the largest multicenter real-world cohort in patients treated with ERV for A. baumannii, where the majority of isolates were CRAB (69.5%). Our analysis demonstrate that patients treated with ERV-based regimens achieved a 30-day mortality of 23.9% and had a low incidence of ERV-possible adverse events (2.1%). This study is important as it fills the gap in the literature regarding the use of a novel tetracycline (i.e., ERV) in the treatment of this challenging health care infection.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Bordetella bronchiseptica Co-Infection in a Stem Cell Transplant Patient.

Bordetella bronchiseptica infections may be overlooked by clinicians due to the uncommon encounter of this pathogen in humans and common isolation of co-pathogens. However, the isolation of B. bronchiseptica in immunocompromised individuals may represent a true infection. We report our experience with the fatal case of a stem cell transplant recipient, co-infected with SARS-CoV-2 and B. bronchiseptica, who was considered fully vaccinated (two doses) at the time of her case in spring 2021. Future studies are needed to evaluate the incidence of bacterial co-infections in immunosuppressed individuals with SARS-CoV-2 and clinicians should remain cognizant of the potential pathogenic role of uncommon pathogens isolated in these individuals.

Activity of Delafloxacin and Levofloxacin against Stenotrophomonas maltophilia at Simulated Plasma and Intrapulmonary pH Values.

Fluoroquinolones have become a popular treatment option for Stenotrophomonas maltophilia infections. Although levofloxacin is most commonly used, delafloxacin demonstrates comparable in vitro activity when evaluated under standard susceptibility testing conditions at neutral pH. At acidic pH, the activity of the anionic delafloxacin is improved, while the activity of the zwitterionic levofloxacin is reduced. Because the human respiratory tract has a pH of ~6.6 and is the most common site of S. maltophilia infection, it is vital to understand the activity of these agents in this environment. Therefore, levofloxacin and delafloxacin were tested against clinical S. maltophilia isolates via broth microdilution testing (n = 37) and time-kill analysis (n = 5) in neutral cation-adjusted Mueller-Hinton broth (CAMHB) (pH 7.3) and acidic CAMHB (aCAMHB) (pH 6.5). In CAMHB, MIC50 values were similar between levofloxacin and delafloxacin (8 mg/L versus 8 mg/L). In aCAMHB, levofloxacin MICs did not change, while delafloxacin MICs decreased by a median of 4 log2 dilutions (MIC50 values of 8 mg/L versus 0.25 mg/L). In time-kill analyses, levofloxacin and delafloxacin at the maximum drug concentration for the free drug (fCmax) were bactericidal against 3 and 2 isolates in CAMHB, respectively. In aCAMHB, levofloxacin was not bactericidal against any isolate, while delafloxacin was bactericidal against the same 2 isolates. Relative to CAMHB, levofloxacin activity was reduced by 2.5 log10 CFU/mL in aCAMHB, whereas delafloxacin activity was increased 2.7 log10 CFU/mL. Although the bactericidal activity of levofloxacin against S. maltophilia was attenuated in an acidic environment in this study, the increased potency of delafloxacin at pH 6.5 did not translate into improved bactericidal activity in time-kill analyses, compared to pH 7.3. IMPORTANCE Stenotrophomonas maltophilia most often infects the lungs, where the physiologic environment is naturally slightly acidic (pH ~6.6), compared to most parts of the body (such as the bloodstream), which have neutral pH values (~7.4). Pneumonia due to S. maltophilia is often treated with the antibiotic levofloxacin, despite the activity of levofloxacin being known to be impaired at acidic pH. Unfortunately, currently available methods for susceptibility testing of levofloxacin against S. maltophilia are performed at a neutral pH and therefore may not accurately represent the activity of levofloxacin at the site of infection in the lungs. A similar but newer antibiotic in the same class as levofloxacin, namely, delafloxacin, is not affected by being in an acidic environment and may actually work better at lower pH values. Therefore, the purpose of this study was to investigate whether one drug might be better than the other in this setting by testing each agent's ability to kill S. maltophilia at pH 7.3 and pH 6.5. These findings could then be used to design confirmatory studies that may ultimately impact which drug is given to patients with lung infections due to S. maltophilia.

Activity of Omadacycline Alone and in Combination against Carbapenem-Nonsusceptible Acinetobacter baumannii with Varying Minocycline Susceptibility.

Tetracycline-based combinations are increasingly used for serious carbapenem-nonsusceptible Acinetobacter baumannii (CNSAb) infections given their potent in vitro activity, synergism with other agents, and acceptable toxicity profile. Omadacycline is a novel aminomethylcycline with activity against minocycline-resistant pathogens, once daily oral dosing, and favorable pharmacokinetic properties. Given these potential advantages, the in vitro potency and antibacterial activity of omadacycline were evaluated alone and in combination against CNSAb with varying minocycline susceptibility. Broth microdilution testing of 41 CNSAb revealed that omadacycline (MIC50/90: 4/8 mg/L) inhibited 68.3% (28/41) of isolates at ≤4 mg/L and its activity was unaffected by minocycline nonsusceptibility (MIC50/90: 4/8 mg/L; 74.2% [23/31] inhibited at ≤4 mg/L). Ten (5 minocycline susceptible and 5 nonsusceptible) of the 41 CNSAb isolates were then evaluated in time-kill analyses against omadacycline and comparator agents alone and in dual- and triple-drug combinations at the free maximum concentration of drug in serum (fCmax). Amikacin, meropenem, and polymyxin B alone were each bactericidal against 4 of 10 (40%) isolates while omadacycline and sulbactam were bactericidal against 0 (0%) and 1 (10%), respectively. In dual-drug combinations with omadacycline, synergy was observed against 80% of isolates with sulbactam followed by 30% with amikacin or polymyxin B and 0% with meropenem or rifampin. The triple-drug combination of omadacycline, sulbactam, and polymyxin B achieved synergy against just one additional strain over the omadacycline-sulbactam dual combination but significantly reduced the time to 99.9% kill by more than 6 h (4.6 ± 2.8 h vs. 11.3 ± 5.9 h, P < 0.01). These results support the continued investigation into tetracycline-based combinations against CNSAb, particularly those including sulbactam, and suggest that omadacycline may have in vitro advantages over existing tetracycline-derivatives. IMPORTANCE Treatment of infections due to Acinetobacter baumannii often involves the use of multiple antibiotics simultaneously as combination therapy, but it is unknown which antibiotics are best used together. Tetracycline agents such as minocycline and tigecycline maintain good activity against A. baumannii and are often used with one or more other agents to achieve better killing of the bacteria. Omadacycline is a new tetracycline that may have a role in the treatment of A. baumannii, but no data are available evaluating its interaction with other commonly used drugs such as polymyxin B and sulbactam. Therefore, the purpose of this study was to investigate the antibacterial activity of omadacycline when combined with one or more other agents against carbapenem-resistant strains of A. baumannii. These findings may then be used to design confirmatory studies that could help decide what drugs work best together and what combination of agents should be used for patients.

Aztreonam in combination with imipenem-relebactam against clinical and isogenic strains of serine and metallo-ß-lactamase-producing enterobacterales.

OBJECTIVE: The objective of this study was to evaluate the in vitro activity of aztreonam plus imipenem-relebactam against clinical and isogenic strains of Escherichia coli and Klebsiella pneumoniae co-harboring NDM and >1 serine ß-lactamase. METHODS: Thirteen isolates were included: 4 clinical E. coli, 4 clinical K. pneumoniae, and 5 isogenic E. coli. Drugs were tested in time-kill analyses alone, in dual ß-lactam combinations, and in triple drug combinations against all strains. RESULTS: All isolates were resistant to imipenem and imipenem-relebactam, and 85% were aztreonam-resistant. Neither imipenem nor imipenem-relebactam was bactericidal alone while aztreonam was bactericidal against 54% of isolates. The combination of aztreonam+imipenem was bactericidal and synergistic against 7/13 and 10/13 isolates. The addition of relebactam to this combination resulted in synergy against all 11 aztreonam-resistant clinical isolates. CONCLUSION: Aztreonam plus imipenem-relebactam may be a viable treatment option for aztreonam-non-susceptible NDM and serine ß-lactamase-producing E. coli and K. pneumoniae.

Early Multicenter Experience With Imipenem-Cilastatin-Relebactam for Multidrug-Resistant Gram-Negative Infections.

A multicenter case series of 21 patients were treated with imipenem-cilastatin-relebactam. There were mixed infection sources, with pulmonary infections (11/21,52%) composing the majority. The primary pathogen was Pseudomonas aeruginosa (16/21, 76%), and 15/16 (94%) isolates were multidrug-resistant. Thirty-day survival occurred in 14/21 (67%) patients. Two patients experienced adverse effects.

Activity of aztreonam in combination with ceftazidime-avibactam against serine- and metallo-ß-lactamase-producing Pseudomonas aeruginosa.

Existing data support the combination of aztreonam and ceftazidime-avibactam against serine-ß-lactamase (SBL)- and metallo-ß-lactamase (MBL)-producing Enterobacterales, although there is a paucity of data against SBL- and MBL-producing Pseudomonas aeruginosa. In this study, 5 SBL- and MBL-producing P. aeruginosa (1 IMP, 4 VIM) were evaluated against aztreonam and ceftazidime-avibactam alone and in combination via broth microdilution and time-kill analyses. All 5 isolates were nonsusceptible to aztreonam, aztreonam-avibactam, and ceftazidime-avibactam. Combining aztreonam with ceftazidime-avibactam at subinhibitory concentrations produced synergy and restored bactericidal activity in 4/5 (80%) isolates tested. These results suggest that the combination of aztreonam and ceftazidime-avibactam may be a viable treatment option against SBL- and MBL-producing P. aeruginosa.

Successful treatment of trichomoniasis with tinidazole following desensitization in a patient allergic to metronidazole.

Metronidazole desensitization is recommended in patients with trichomoniasis and history of an allergic reaction to metronidazole due to presumed cross reactivity with tinidazole and lack of reliably safe and effective alternative therapies. We report our experiences in a patient with persistent trichomoniasis who failed to complete metronidazole desensitization due to a burning sensation over her whole body and pruritus but was later successfully desensitized to tinidazole without experiencing any adverse effects.

Development of a 51-hospital Chicagoland regional antibiogram and comparison to local hospital and national surveillance data.

OBJECTIVE: To develop a regional antibiogram within the Chicagoland metropolitan area and to compare regional susceptibilities against individual hospitals within the area and national surveillance data. DESIGN: Multicenter retrospective analysis of antimicrobial susceptibility data from 2017 and comparison to local institutions and national surveillance data. SETTING AND PARTICIPANTS: The analysis included 51 hospitals from the Chicago-Naperville-Elgin Metropolitan Statistical Area within the state of Illinois. Overall, 18 individual collaborator hospitals provided antibiograms for analysis, and data from 33 hospitals were provided in aggregate by the Becton Dickinson Insights Research Database. METHODS: All available antibiogram data from calendar year 2017 were combined to generate the regional antibiogram. The final Chicagoland antibiogram was then compared internally to collaborators and externally to national surveillance data to assess its applicability and utility. RESULTS: In total, 167,394 gram-positive, gram-negative, fungal, and mycobacterial isolates were collated to create a composite regional antibiogram. The regional data represented the local institutions well, with 96% of the collaborating institutions falling within ±2 standard deviations of the regional mean. The regional antibiogram was able to include 4-5-fold more gram-positive and -negative species with ≥30 isolates than the median reported by local institutions. Against national surveillance data, 18.6% of assessed pathogen-antibiotic combinations crossed prespecified clinical thresholds for disparity in susceptibility rates, with notable trends for resistant gram-positive and gram-negative bacteria. CONCLUSIONS: Developing an accurate, reliable regional antibiogram is feasible, even in one of the largest metropolitan areas in the United States. The biogram is useful in assessing susceptibilities to less commonly encountered organisms and providing clinicians a more accurate representation of local antimicrobial resistance rates compared to national surveillance databases.

Multidrug Resistant Acinetobacter baumannii: Resistance by Any Other Name Would Still be Hard to Treat.

PURPOSE OF REVIEW: Acinetobacter baumannii (AB) is an infamous nosocomial pathogen with a seemingly limitless capacity for antimicrobial resistance, leading to few treatment options and poor clinical outcomes. The debatably low pathogenicity and virulence of AB are juxtaposed by its exceptionally high rate of infection-related mortality, likely due to delays in time to effective antimicrobial therapy secondary to its predilection for resistance to first-line agents. Recent studies of AB and its infections have led to a burgeoning understanding of this critical microbial threat and provided clinicians with new ammunition for which to target this elusive pathogen. This review will provide an update on the virulence, resistance, diagnosis, and treatment of multidrug resistant (MDR) AB. RECENT FINDINGS: Advances in bacterial genomics have led to a deeper understanding of the unique mechanisms of resistance often present in MDR AB and how they may be exploited by new antimicrobials or optimized combinations of existing agents. Further, improvements in rapid diagnostic tests (RDTs) and their more pervasive use in combination with antimicrobial stewardship interventions have allowed for more rapid diagnosis of AB and decreases in time to effective therapy. Unfortunately, there remains a paucity of high-quality clinical data for which to inform the optimal treatment of MDR AB infections. In fact, recently completed studies have failed to identify a combination regimen that is consistently superior to monotherapy, despite the benefits demonstrated in vitro. Encouragingly, new and updated guidelines offer strategies for the treatment of MDR AB and may help to harmonize the use of high toxicity agents such as the polymyxins. Finally, new antimicrobial agents such as eravacycline and cefiderocol have promising in vitro activity against MDR AB but their place in therapy for these infections remains to be determined. Notwithstanding available clinical trial data, polymyxin-based combination therapies with either a carbapenem, minocycline, or eravacycline remain the treatment of choice for MDR, particularly carbapenem-resistant, AB. Incorporating antimicrobial stewardship intervention with RDTs relevant to MDR AB can help avoid potentially toxic combination therapies and catalyze the most important modifiable risk factor for mortality-time to effective therapy. Further research efforts into pharmacokinetic/pharmacodynamic-based dose optimization and clinical outcomes data for MDR AB continue to be desperately needed.

Impact of an HIV-trained clinical pharmacist intervention on error rates of antiretroviral and opportunistic infection medications in the inpatient setting.

BACKGROUND: Based on a retrospective study performed at our institution, 38% of inpatients living with human immunodeficiency virus (HIV) were found to have a medication error involving their anti-retroviral (ARV) and/or opportunistic infection (OI) prophylaxis medications. OBJECTIVE: To determine the impact of a dedicated HIV-trained clinical pharmacist on the ARV and OI prophylaxis medication error rates at our institution. METHODS: A prospective quality improvement project was conducted over a six month period to assess the impact of a dedicated HIV-trained clinical pharmacist on the ARV and OI prophylaxis medication error rates. IRB approval received. RESULTS: There were 144 patients included in this analysis, who experienced a combined 76 medication errors. Compared to historical control study conducted at our institution, the percent of patients who experienced a medication error remained stable (38% vs. 39%, respectively) and the error rate per patient was similar (1.44 vs. 1.36, p=NS). The percent of medication errors that were corrected prior to discharge increased from 24% to 70% and the median time to error correction decreased from 42 hours to 11.5 hours (p<0.0001). CONCLUSIONS: Errors relating to ARV or OI prophylaxis medications remain frequent in inpatient people living with HIV/AIDS. After multiple interventions were implemented, ARV and OI prophylaxis medication errors were corrected faster and with greater frequency prior to discharge, however, similar rates of errors for patients existed. Dedicated HIV clinicians with adequate training and credentialing are necessary to manage this specialized disease state and to reduce the overall number of medication errors associated with HIV/AIDS.

Impact of an HIV-trained clinical pharmacist intervention on error rates of antiretroviral and opportunistic infection medications in the inpatient setting

Background: Based on a retrospective study performed at our institution, 38% of inpatients living with human immunodeficiency virus (HIV) were found to have a medication error involving their anti-retroviral (ARV) and/or opportunistic infection (OI) prophylaxis medications. Objective: To determine the impact of a dedicated HIV-trained clinical pharmacist on the ARV and OI prophylaxis medication error rates at our institution. Methods: A prospective quality improvement project was conducted over a six month period to assess the impact of a dedicated HIV-trained clinical pharmacist on the ARV and OI prophylaxis medication error rates. IRB approval received. Results: There were 144 patients included in this analysis, who experienced a combined 76 medication errors. Compared to historical control study conducted at our institution, the percent of patients who experienced a medication error remained stable (38% vs. 39%, respectively) and the error rate per patient was similar (1.44 vs. 1.36, p=NS). The percent of medication errors that were corrected prior to discharge increased from 24% to 70% and the median time to error correction decreased from 42 hours to 11.5 hours (p<0.0001). Conclusions: Errors relating to ARV or OI prophylaxis medications remain frequent in inpatient people living with HIV/AIDS. After multiple interventions were implemented, ARV and OI prophylaxis medication errors were corrected faster and with greater frequency prior to discharge, however, similar rates of errors for patients existed. Dedicated HIV clinicians with adequate training and credentialing are necessary to manage this specialized disease state and to reduce the overall number of medication errors associated with HIV/AIDS

No disponible

Development of High-Level Echinocandin Resistance in a Patient With Recurrent Candida auris Candidemia Secondary to Chronic Candiduria.

OBJECTIVE: Candida auris is a globally emerging pathogen associated with significant mortality. This pathogen frequently is misidentified by traditional biochemical methods and is resistant to commonly used antifungals. The echinocandins currently are recommended as the first-line treatment for C. auris infections. The objective of this work is to demonstrate the challenges associated with C. auris in the real-world setting. METHODS: A 54-year-old male presented to our institution for concerns of sepsis on multiple occasions over a 5-month period. Eleven urine cultures were positive over this timeframe for yeast (9 unidentified Candida isolates and 2 C. lusitaniae isolates). On day 27, the patient developed echinocandin-susceptible candidemia, which was initially identified as C. haemulonii but later accurately identified as C. auris at an outside mycology reference laboratory. Approximately 10 weeks later, the patient had a recurrence of candidemia, this time caused by an echinocandin-resistant C. auris strain. RESULTS: Genomic DNA sequencing performed at the outside mycology reference laboratory identified a single serine to proline base pair change at position 639 (S639P) in the hotspot 1 region of the FKS1 gene of the echinocandin-resistant strain. CONCLUSIONS: Our experiences highlight 4 major concerns associated with C. auris: misidentification, persistent colonization, infection recurrence despite the receipt of appropriate initial therapy, and development of resistance.

A Breath of Fresh Air in the Fog of Antimicrobial Resistance: Inhaled Polymyxins for Gram-Negative Pneumonia.

Despite advancements in therapy, pneumonia remains the leading cause of death due to infectious diseases. Novel treatment strategies are desperately needed to optimize the antimicrobial therapy of patients suffering from this disease. One such strategy that has recently garnered significant attention is the use of inhaled antibiotics to rapidly achieve therapeutic concentrations directly at the site of infection. In particular, there is significant interest in the role of inhaled polymyxins for the treatment of nosocomial pneumonia, including ventilator-associated pneumonia, due to their retained activity against multi-drug resistant Gram-negative pathogens, including Acinetobacter baumannii and Pseudomonas aeruginosa. This review will provide a comprehensive overview of the pharmacokinetic/pharmacodynamic profile, clinical outcomes, safety, and potential role of inhaled polymyxins in clinical practice.

Pharmacokinetic evaluation of meropenem and vaborbactam for the treatment of urinary tract infection.

INTRODUCTION: Meropenem/vaborbactam (M/V) represents the first carbapenem and ß-lactamase inhibitor combination approved for treatment of complicated urinary tract infections (cUTIs), including pyelonephritis. Vaborbactam is a novel boronic acid, ß-lactamase inhibitor with a high affinity for serine ß-lactamases, including Klebsiella pneumoniae carbapenemase (KPC). This combination, Vabomere™, was approved in August 2017 by the United States Food and Drug Administration for the treatment of cUTIs in patients 18 years or older, including pyelonephritis, caused by the following susceptible microorganisms: Escherichia coli, K. pneumoniae, and Enterobacter cloacae species complex. Areas covered: Relevant literature regarding microbiology, pharmacokinetics, pharmacodynamics, and clinical trials evaluating efficacy, safety, and tolerability will be discussed. Expert opinion: Current treatment options for KPC-producing infections such as aminoglycosides, polymyxins, fosfomycin, and tigecycline are associated with concerns regarding efficacy, toxicities, optimal dosing, and/or development of resistance. Additionally, resistance to the new combination product of ceftazidime/avibactam has also emerged. Current clinical evidence supporting the use of M/V for KPC-producing infections is limited to an open-label, randomized, phase III study in a small number of patients with serious infections due to carbapenem-resistant Enterobacteriaceae. Although M/V is not approved for KPC-producing infections, we believe that M/V will become a preferred agent for KPC-producing Enterobacteriaceae infections.

New Antiretroviral Treatment for HIV.

The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set the global goal of ending the AIDS world epidemic by 2030. In order to end this epidemic they have established a 90-90-90 goal to be achieved by 2020, which may be problematic, especially in low- and middle-income countries. This goal includes 90% of individuals with HIV globally being diagnosed, on treatment, and virologically suppressed. Based on global estimates from 2014-2015, approximately 36.9 million individuals are living with HIV. Of those, 53% have been diagnosed with HIV, 41% are on antiretroviral therapy (ART), and 32% have viral suppression with <1000 copies/ml. Comprehensive approaches are needed to improve the number of people living with HIV (PLWH) who are diagnosed, linked, and engaged in care. Once PLWH are retained in care, treatment is key to both HIV prevention and transmission. The development and advancement of new ART is necessary to assist in reaching these goals by improving safety profiles, decreasing pill burden, improving quality of life and life expectancy, and creating new mechanisms to overcome resistance. The focus of this review is to highlight and review data for antiretroviral agents recently added to the market as well as discuss agents in various stages of development (new formulations and mechanisms of action).