Broad-spectrum antimicrobial consumption trends and correlation with bacterial infections and antimicrobial resistance over 5 years.

OBJECTIVES: Consumption trends of four broad-spectrum antimicrobials and their correlation with antimicrobial resistance in Gram-negative bacilli (GNB) from 2013-2017 within intensive care units (ICUs) were explored. METHODS: Consumption of meropenem (MEM), polymyxin B (PMB), piperacillin/tazobactam (TZP) and cefepime (FEP) in defined daily doses per 1000 patient-days (DDD/1000PD) was measured. Infection-related GNB isolates were grouped according to specific resistance profiles. Time series of antimicrobial consumption and their parametric correlation with each grouped resistant GNB were explored. RESULTS: A total of 1423 GNB were evaluated. A significant linear decline in consumption was observed for MEM [slope -3.88, 95% confidence interval (CI) -4.96 to -2.81; P < 0.0001] and PMB (slope -3.51, 95% CI -5.528 to -1.495; P = 0.0009). A significant decline in MEM-non-susceptible Acinetobacter spp. (R2 = 0.476; P = 0.006) and an increase in FEP-non-susceptible Escherichia coli (R2 = 0.124; P = 0.006) was observed. A significant correlation between MEM consumption and MEM-non-susceptible Acinetobacter spp. (r = 0.43; P = 0.001) was observed. MEM consumption and MEM-non-susceptible Acinetobacter spp. showed a positive correlation. CONCLUSION: Reduction in the consumption of broad-spectrum antimicrobials may alter the frequency of infection-related isolates and their antimicrobial resistance profiles.

Evaluation of high-concentration EDTA-modified carbapenemase inactivation method (eCIM) for SPM-producing Pseudomonas aeruginosa.

The modified carbapenemase inactivation method (mCIM) and EDTA-modified carbapenemase inactivation method (eCIM) are simple and cost-effective detection methods used for serine- and metallo-carbapenemase determination; however, poor test performance has been reported for IMP- and SPM-producing P. aeruginosa. Recently, we reported that 40 µM EDTA concentrations improved test sensitivity for IMP-producing P. aeruginosa. Herein, we assessed standard and high-concentration EDTA eCIM against SPM-producing P. aeruginosa. Twenty-four SPM-producing P. aeruginosa were evaluated, and 3 well-characterized P. aeruginosa (wild type, n = 1; KPC, n = 1; and VIM, n = 1) were used for quality control. mCIM was conducted as described by the Clinical and Laboratory Standards Institute. Concurrently, eCIM methods were performed at standard (5 µM) and high (40 µM) EDTA concentrations. All mCIM phenotypes responded concordant with its genotype. eCIM phenotype matched its genotype for 3 and 24 SPM-producing isolates using standard and high EDTA concentrations, respectively. The eCIM sensitivity increased from 12% using standard concentrations to 100% using high EDTA concentrations. No EDTA-related adverse effects were observed on bacteria growth. The combination mCIM with 40 µM EDTA eCIM properly captured SPM-producing P. aeruginosa. This methodology should be validated in a multi-center study with various enzymatic-producing P. aeruginosa.

In vitro synergy of ticarcillin/clavulanate in combination with aztreonam and ceftolozane/tazobactam against SPM-1-producing Pseudomonas aeruginosa strains.

Minimal inhibitory concentrations (MICs) of ticarcillin/clavulanic acid (TLc), ceftolozane/tazobactam (C/T), and aztreonam (AT) were determined for 6 SPM-1-producing Pseudomonas aeruginosa (PSA) using Etest® strips and the synergistic effect of such antimicrobials against was evaluated by gradient diffusion strip crossing (GDSC) test. The fraction inhibitory concentration indexes (FICI) were calculated and showed a synergistic (n = 3) and additive (n = 2) effects of TLc + AT against SPM-1 producers, while TLc + C/T combination caused no effect. Average MIC reduction of TLc and AT by GDSC was 3-fold and 2-fold dilutions, respectively. Thus, TLc + AT might be a candidate as a combination therapy to treat SPM-1-producing PSA infections.

In vitro synergy of ceftolozane/tazobactam in combination with fosfomycin or aztreonam against MDR Pseudomonas aeruginosa.

OBJECTIVES: Carbapenem-resistant Pseudomonas aeruginosa (CR-PSA) imposes great limitations on empirical therapeutic choices, which are further complicated by metallo-ß-lactamase production. This study evaluated in vitro antimicrobial synergy of ceftolozane/tazobactam in combination with aztreonam and fosfomycin against MDR PSA. METHODS: MICs were determined by broth microdilution and gradient strips. The effect of ceftolozane/tazobactam+aztreonam and ceftolozane/tazobactam+fosfomycin combinations were tested against 27 MDR PSA isolates carrying blaSPM-1 (n = 13), blaIMP (n = 4), blaVIM (n = 3), blaGES-1 (n = 2) and blaCTX-M-like (n = 2), and 3 isolates with no acquired ß-lactamase production detected by gradient diffusion strip crossing (GDSC). Six genetically unrelated SPM-1-producing isolates were also evaluated by time-kill analysis (TKA). RESULTS: All CR-PSA isolates harbouring blaSPM-1, blaGES-1 and blaIMP-1 were categorized as resistant to ceftolozane/tazobactam, meropenem and fosfomycin, with 70% being susceptible to aztreonam. Synergism for ceftolozane/tazobactam+fosfomycin and ceftolozane/tazobactam+aztreonam combinations was observed for 88.9% (24/27) and 18.5% (5/27) of the isolates by GDSC, respectively. A 3- to 9-fold reduction in ceftolozane/tazobactam MICs was observed, depending on the combination. Ceftolozane/tazobactam+fosfomycin was synergistic by TKA against one of six SPM-1-producing isolates, with additional non-synergistic bacterial density reduction for another isolate. Aztreonam peak concentrations alone demonstrated a ≥3 log10 cfu/mL reduction against all six isolates, but all strains were within the susceptible range for the drug. No antagonism was observed. CONCLUSIONS: In the context of increasing CR-PSA and the genetic diversity of resistance mechanisms, new combinations and stewardship strategies may need to be explored in the face of increasingly difficult to treat pathogens.

Natural experiment of syphilis treatment with doxycycline or benzathine penicillin in HIV-infected patients.

BACKGROUND: Although doxycycline is widely used as an alternative to benzathine penicillin for the treatment of early and late latent syphilis, data on serological response following treatment with doxycycline among HIV-infected patients are limited. METHODS: In this study, we analysed serological response to syphilis treatment with doxycycline among HIV-infected patients treated during a benzathine penicillin shortage period and compared with treatment response among patients treated with benzathine penicillin. Cases with neurosyphilis and those treated with suboptimal doses or with concurrent medications in association with benzathine penicillin or doxycycline were excluded. RESULTS: Fifty patients treated with doxycycline from September 2014 to December 2016 were compared with 115 patients treated with benzathine penicillin for early, late latent or latent syphilis of unknown duration. Patients treated with doxycycline were slightly older [(median 49 years old, 95% confidence interval (95% CI) 43-56] than those in the penicillin group (median 44 years old, 95% CI 37-50; P = 0.007). Groups had no statistically significant differences regarding sex, HIV suppression under treatment and syphilis stages. Serological response to treatment, defined as a nonreagent Venereal Disease Research Laboratory (VDRL) or at least a four-fold reduction in VDRL titres measured 6-12 months after treatment, was seen in 72% (95% CI 58-84) of patients treated with doxycycline and 70% (95% CI 60-78) of patients treated with penicillin (P = 0.753). CONCLUSION: We found no statistically significant differences in serological response to treatment with doxycycline or benzathine penicillin among HIV-infected patients with early, late latent or latent syphilis of unknown duration. Our findings suggest that doxycycline is an acceptable treatment to HIV-infected patients with nontertiary stages of syphilis.