Case Report: Successful Treatment of Recurrent Urinary Tract Infection Due to Extensively Drug-Resistant Klebsiella Pneumoniae in a Kidney Transplant Recipient Using Chloramphenicol.

Effective therapies for multidrug-resistant (MDR) microorganisms, especially Gram-negative bacteria, are becoming rare. Also, solid-organ transplant recipients are at high risk of MDR Gram-negative bacilli infection. Urinary tract infections are the most frequent bacterial infections in kidney transplant recipients and are an important cause of mortality after renal transplantation. We describe a case of complicated urinary tract infection in a kidney transplant patient due to extensively drug-resistant (XDR) K. pneumoniae treated successfully with a regimen comprising a combination of chloramphenicol and ertapenem. We do not recommend chloramphenicol as a first-line choice for treating complicated urinary tract infections. Still, we believe it is an alternative for infections caused by MDR and/or XDR pathogens in renal transplant patients, as other options are nephrotoxic.

Colistin-resistant Escherichia coli belonging to different sequence types: genetic characterization of isolates responsible for colonization, community- and healthcare-acquired infections.

The plasmid-mediated colistin-resistance gene named mcr-1 has been recently described in different countries and it became a public health challenge. Of note, few studies have addressed the spread of Escherichia coli harboring the mcr-1 gene in both, community and hospital settings. A total of seven colistin-resistant E. coli carrying mcr-1, collected from 2016 to 2018, from community (n=4), healthcare-acquired infections (n=2) and colonization (n=1) were identified in three high complexity hospitals in Sao Paulo, Brazil. These colistin-resistant isolates were screened for mcr genes by PCR and all strains were submitted to Whole Genome Sequencing and the conjugation experiment. The seven strains belonged to seven distinct sequence types (ST744, ST131, ST69, ST48, ST354, ST57, ST10), and they differ regarding the resistance profiles. Transference of mcr-1 by conjugation to E. coli strain C600 was possible in five of the seven isolates. The mcr-1 gene was found in plasmid types IncX4 or IncI2. Three of the isolates have ESBL-encoding genes (blaCTX-M-2, n=2; blaCTX-M-8, n=1). We hereby report genetically distinct E. coli isolates, belonging to seven STs, harboring the mcr-1 gene, associated to community and healthcare-acquired infections, and colonization in patients from three hospitals in Sao Paulo. These findings point out for the potential spread of plasmid-mediated colistin-resistance mechanism in E. coli strains in Brazil.

Pharmacokinetic and Pharmacodynamic Characteristics of Vancomycin and Meropenem in Critically Ill Patients Receiving Sustained Low-efficiency Dialysis.

PURPOSE: Antibiotic dosing is challenge in critically ill patients undergoing renal replacement therapy. Our aim was to evaluate the pharmacokinetic and pharmacodynamic (PK/PD) characteristics of meropenem and vancomycin in patients undergoing SLED. METHODS: Consecutive ICU patients undergoing SLED and receiving meropenem and/or vancomycin were prospectively evaluated. Serial blood samples were collected before, during, and at the end of SLED sessions. Antimicrobial concentrations were determined using a validated HPLC method. Noncompartmental PK analysis was performed. AUC was determined for vancomycin. For meropenem, time above MIC was calculated. FINDINGS: A total of 24 patients receiving vancomycin and 21 receiving meropenem were included; 170 plasma samples were obtained. Median serum vancomycin and meropenem concentrations before SLED were 24.5 and 28.0 µg/mL, respectively; after SLED, 14 and 6 µg/mL. Mean removal was 42% with vancomycin and 78% with meropenem. With vancomycin, 19 (83%), 16 (70%), and 15 (65%) patients would have achieved the target (AUC0-24 >400) considering MICs of 1, 2, and 4 mg/L, respectively. With meropenem, 17 (85%), 14 (70%), and 10 (50%) patients would have achieved the target (100% of time above MIC) if infected with isolates with MICs of 1, 4, and 8 mg/L, respectively. IMPLICATIONS: SLED clearances of meropenem and vancomycin were 3-fold higher than the clearance described by continuous methods. Despite this finding, overall high PK/PD target attainments were obtained, except for at higher MICs. We suggest a maintenance dose of 1 g TID or BID of meropenem. With vancomycin, a more individualized approach using therapeutic drug monitoring should be used, as commercial assays are available.

Clinical Outcome and Antimicrobial Therapeutic Drug Monitoring for the Treatment of Infections in Acute Burn Patients.

PURPOSE: In critical burn patients, the pharmacokinetic parameters (absorption, distribution, metabolism, and excretion) of many classes of drugs, including antibiotics, are altered. The aim of this study was to compare 2 groups of burn patients undergoing treatment for health care-associated infections with and without therapeutic drug monitoring. METHODS: A retrospective analysis of a clinical intervention (ie, a before/after study) was conducted with patients with health care-associated pneumonia, burn infection, bloodstream infection, and urinary tract infection in the burn intensive care unit of a tertiary care hospital. The patients were divided into 2 groups: (1) those admitted from May 2005 to October 2008 who received conventional antimicrobial dose regimens; and (2) those admitted from November 2008 to June 2011 who received antibiotics (imipenem, meropenem, piperacillin, and vancomycin) with doses adjusted according to plasma monitoring and pharmacokinetic modeling. General characteristics of the groups were analyzed, as were clinical outcomes and 14-day and in-hospital mortality. FINDINGS: Sixty-three patients formed the conventional treatment group, and 77 comprised the monitored treatment group. The groups were homogeneous, median age was 31 years (range: 1-90) and 66% were male. Improvement occurred in 60% of the patients under monitored treatment (vs 52% with conventional treatment); 14-day mortality was 16% vs 14%; and the in-hospital mortality was similar between groups (39% vs 36%). In the final multivariate models, variables significantly associated with in-hospital mortality were total burn surface area ≥30%, older age, and male sex. Treatment group did not affect the prognosis. IMPLICATIONS: Therapeutic drug monitoring of antimicrobial treatment did not alter the prognosis of these burn patients. More trials are needed to support the use of therapeutic drug monitoring to optimize treatment in burn patients.

Surveillance culture for multidrug-resistant gram-negative bacteria: Performance in liver transplant recipients.

BACKGROUND: The prevalence of infection with multidrug-resistant gram-negative bacteria (MDR-GNB) after solid-organ transplantation is increasing. Surveillance culture (SC) seems to be an important tool for MDR-GNB control. The goal of this study was to analyze the performance of SC for MDR-GNB among liver transplant (LT) recipients. METHODS: This was a prospective cohort study involving patients who underwent LT between November 2009 and November 2011. We screened patients for extended spectrum ß-lactamase-producing Escherichia coli, extended spectrum ß-lactamase-producing Klebsiella pneumoniae, and carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Acinetobacter baumannii (CRAB). We collected SC samples immediately before LT and weekly thereafter, until hospital discharge. Samples were collected from the inguinal-rectal area, axilla, and throat. The performance of SC was evaluated through analysis of its sensitivity, negative predictive value, and accuracy. RESULTS: During the study period, 181 patients were evaluated and 4,110 SC samples were collected. The GNB most often identified was CRAB, in 45.9% of patients, followed by CRKP in 40.3%. For all microorganisms, the positivity rate was highest among the inguinal-rectal samples. If only samples collected from this area were considered, the SC would fail to identify 34.9% of the cases of CRAB colonization. The sensitivity of SC for CRKP was 92.5%. The performance of SC was poorest for CRAB (sensitivity, 80.6%). CONCLUSIONS: Our data indicate that SC is a sensitive tool to identify LT recipients colonized by MDR-GNB.

Carbapenem-resistant Acinetobacter baumannii acquired before liver transplantation: Impact on recipient outcomes.

Infection with carbapenem-resistant Acinetobacter baumannii (CRAB) after liver transplantation (LT) is associated with high mortality. This study aimed to identify risk factors for post-LT CRAB infection, as well as to evaluate the impact of pre-LT CRAB acquisition on the incidence of post-LT CRAB infection. This was a prospective cohort study of all patients undergoing LT at our facility between October 2009 and October 2011. Surveillance cultures (SCs) were collected immediately before LT and weekly thereafter, until discharge. We analyzed 196 patients who were submitted to 222 LTs. CRAB was identified in 105 (53.6%); 24 (22.9%) of these patients were found to have acquired CRAB before LT, and 85 (81.0%) tested positive on SCs. Post-LT CRAB infection occurred in 56 (28.6%), the most common site being the surgical wound. Multivariate analysis showed that the risk factors for developing CRAB infection were prolonged cold ischemia, post-LT dialysis, LT due to fulminant hepatitis, and pre-LT CRAB acquisition with pre-LT CRAB acquisition showing a considerable trend toward significance (P = 0.06). Among the recipients with CRAB infection, 60-day mortality was 46.4%, significantly higher than among those without (P < 0.001). Mortality risk factors were post-LT infection with multidrug-resistant bacteria, LT performed because of fulminant hepatitis, retransplantation, prolonged cold ischemia, longer LT surgical time, and pre-LT CRAB acquisition, the last showing a trend toward significance (P = 0.08). In conclusion, pre-LT CRAB acquisition appears to increase the risk of post-LT CRAB infection, which has a negative impact on recipient survival. Liver Transplantation 22 615-626 2016 AASLD.

Primary cutaneous cryptococcosis caused by Cryptococcus gattii in an immunocompetent host.

This paper presents the case of a 75-year-old Brazilian man who developed inflammatory skin lesions with nodules and ulcerations on the right forearm after an injury caused by handling barbed-wire and Eucalyptus spp. logs. Histopathological assessment of the lesions showed granulomatous processes with yeasts similar to Cryptococcus spp. Tissue fragments yielded yeasts when cultured that were identified as Cryptococcus gattii VGII through biochemical reactions and URA5-RFLP genotype. No evidence of systemic involvement or any underlying immunosuppressive diseases were identified, which supported the diagnosis of primary cutaneous cryptococcosis. After 5 months on therapy with high fluconazole doses, the skin lesions had fully healed.