Synergistic Antibacterial Effects of Meropenem in Combination with Aminoglycosides against Carbapenem-Resistant Escherichia coli Harboring blaNDM-1 and blaNDM-5

Infections due to carbapenem-resistant Escherichia coli (CREC) are problematic due to limitation in treatment options. Combination therapies of existing antimicrobial agents have become a reliable strategy to control these infections. In this study, the synergistic effects of meropenem in combination with aminoglycosides were assessed by checkerboard and time-kill assays. Of the 35 isolates, 19 isolates (54.3%) were resistant to carbapenems (imipenem and meropenem) with the MIC ranges from 16 to 128 µg/mL. These isolates were resistant to almost all antibiotic classes. Molecular characteristics revealed co-harboring of carbapenemase (blaNDM-1, blaNDM-5 and blaOXA-48) and extended-spectrum β-lactamases (ESBL) genes (blaCTX-M, blaSHV and blaTEM). The checkerboard assay displayed synergistic effects of meropenem and several aminoglycosides against most CREC isolates. Time-kill assays further demonstrated strong synergistic effects of meropenem in combination with either amikacin, gentamicin, kanamycin, streptomycin, and tobramycin. The results suggested that meropenem in combination with aminoglycoside therapy might be an efficient optional treatment for infections cause by CREC.

Use of Doxycycline in a Renal Impaired Patient with Enteroccocal Sepsis

Aim: This report highlights the use of doxycycline therapy other than the more standard regimen that includes an aminoglycoside in the management of enterococcal infection in patients with renal impairment without causing further damages to the kidney due to aminoglycoside therapy. Presentation of Case: A case of enteroccocal septicemia in a 29-year-old woman who was admitted on account of acute kidney injury secondary to pregnancy induced hypertension in the setting of pre-eclampsia. She was referred from another centre where she had emergency caesarean section done on account of severe pre-eclampsia at 36 weeks gestational age. Blood culture yielded Enterococcus species. When other antibiotic regimen failed, she was started on doxycycline. Patient had good clinical response and was discharged 7 days after commencement of doxycycline. Discussion: Enteroccoci have emerged as important agent of human disease largely because of their resistance to antimicrobial agents. They are important nosocomial pathogens capable of causing serious and potentially life-threatening infections, including sepsis. The incidence of enteroccocal infections, mainly hospital-acquired, has increased over the past 2 decades and isolates with novel mechanism of resistance to antimicrobial agents are more and more frequent. Furthermore, they have great capacity for transmitting these resistances to other species and even to other genera. Conclusion: Doxycycline is a safe and effective alternative antibiotic for the treatment of enterococcal sepsis in patients with impaired renal status.

Rhizobium radiobacter bacteremia in a two-year-old patient with an acute lymphoblastic leukemia: a case report

Rhizobium radiobacter is a Gram-negative rod-shaped bacterium usually associated with diseases in plants. Infections due to R. radiobacter in humans are strongly related to the presence of foreign plastic materials, immunocompromised and chronically debilitated hosts with underlying conditions such as malignancies, human immunodeficiency virus as well as bone marrow transplant recipients. The aim of this paper was to present a rare blood infection with Rhizobium radiobacter in North Macedonia in a pediatric patient with underlying conditions. The treatment was successful with appropriate cephalosporin and aminoglycoside therapy without removing the central venous catheter

Infective Endocarditis Guidelines: The Challenges of Adherence—A Survey of Infectious Diseases Clinicians

Background Guidelines exist to aid clinicians in managing patients with infective endocarditis (IE), but the degree of adherence with guidelines by Infectious Disease (ID) physicians is largely unknown. Methods An electronic survey assessing adherence with selected IE guidelines was emailed to 1409 adult ID physician members of the Infectious Diseases Society of America’s Emerging Infections Network. Results Five hundred fifty-seven physicians who managed IE responded. Twenty percent indicated that ID was not consulted on every case of IE at their hospitals, and 13% did not recommend transthoracic echocardiography (TTE) for all IE cases. The duration of antimicrobial therapy was timed from the first day of negative blood cultures by 91% of respondents. Thirty-four percent of clinicians did not utilize an aminoglycoside for staphylococcal prosthetic valve IE (PVE). Double β-lactam therapy was “usually” or “almost always” employed by 83% of respondents for enterococcal IE. For patients with active IE who underwent valve replacement and manifested positive surgical cultures, 6 weeks of postoperative antibiotics was recommended by 86% of clinicians. Conclusions The finding that adherence was <90% with core guideline recommendations that all patients with suspected IE be seen by ID and that all patients undergo TTE is noteworthy. Aminoglycoside therapy of IE appears to be declining, with double β-lactam regimens emerging as the preferred treatment for enterococcal IE. The duration of postoperative antimicrobial therapy for patients undergoing valve replacement during acute IE is poorly defined and represents an area for which additional evidence is needed.

Prevalence of aminoglycoside therapy and other determinant factors that induce hearing loss in neonates

<p class="abstract"><strong>Background:</strong> Hearing loss is the most common disorder in neonates; it can be best managed if it is diagnosed at early stage of life. The global prevalence of permanent neonatal hearing loss mainly occurs in developing countries, which accounts 0.5 to 5.0 per 1000 live births. The objective of this study was to determine the prevalence of aminoglycoside therapy and other risk factors that induce hearing loss in neonates admitted at NICU at Cipto-Mangunkusumo General Hospital (CMGH).</p><p class="abstract"><strong>Methods:</strong> This was a case-control study conducted among 112 neonates at Cipto-Mangunkusumo General Hospital (CMGH). Data from neonatal hearing screening were retrospectively collected from hospital electronic medical records and medical files. Only patients treated at neonatal unit from November 2018 to October 2019 were recruited. </p><p class="abstract"><strong>Results:</strong> Out of 112 neonates studied, the gestational age at birth (GA) and craniofacial anomalies were considered risk factors for hearing loss since they were statistically significant (p&lt;0.05). The study showed no statistical significant association in gender, birth weight, mechanical ventilation, NICU stay period (&gt;5 days), hyperbilirubinemia (&gt;20 mg/dl), asphyxia, and aminoglycoside therapy (p&gt;0.05).</p><p class="abstract"><strong>Conclusions:</strong> The prevalence of hearing loss in neonates with lower gestational age less than 37 weeks and craniofacial anomalies are significant higher compare to neonates born full term. They are more associated with 3 and 6 times increased risk of hearing loss in neonates.</p>

A study of effect of aminoglycoside therapy on auditory brainstem evoked responses in preterm and term neonates

Background: Aminoglycosides are widely used drugs in neonates with associated ototoxic side effects, that can be diagnosed with auditory brainstem evoked responses, which is the recommended screening technique in neonatal intensive care unit infants. This study was conducted to evaluate the effect of aminoglycoside therapy on auditory brainstem evoked responses in term and preterm neonates.Methods: A cross-sectional case control study. Two groups of 26 term and 22 preterm neonates who received aminoglycosides, with no other known risk factors for ototoxicity, were compared with suitable matched control group of 10 neonates in each. ABER was done after at least 5 days of aminoglycoside therapy and results were compared to suitable matched controls.Results: Mean latency of wave I in term neonates at 90 dB and 60 dB and mean interwave latencies of I-V waves in preterm neonates at 30 dB was higher in study group and statistically significant. No statistically significant difference in any of ABER parameters was observed in any group, at all other intensities.Conclusions: Wave I latency was prolonged in study group of term neonates at two intensities which indicates effect of aminoglycoside therapy on distal portion of acoustic nerve. But as there were no such findings at other intensities in term study group and in preterm study group and moreover no other ABER abnormalities were observed, it was concluded that the aminoglycoside therapy has low potential for ototoxicity. Authors support the ABER screening for early detection of hearing abnormalities, and recommend study on larger group of neonates and meta-analysis for final conclusion for evidence-based recommendations to use aminoglycosides in neonates, in view of audiometric and neurological abnormalities.

Evaluation of the clinical practice of aminoglycoside use in paediatric patients in Kenya: findings and implications for lower-middle income countries

Objectives To evaluate the practice of aminoglycoside use/monitoring in Kenya and explore healthcare worker (HCW) perceptions of aminoglycoside monitoring to identify gaps and opportunities for future improvements, given the low therapeutic index of aminoglycosides. Methods This was a two-phase study whereby we reviewed patients’ medical records at Kenyatta National Hospital (October–December 2016) in Phase 1 and interviewed HCWs face to face in Phase 2. Outcome measures included describing and evaluating the practice of aminoglycoside use and monitoring and compliance to guidelines. Data were analysed using descriptive and inferential analysis. Results Overall, out of the 2318 patients admitted, 192 patients (8.3%) were prescribed an aminoglycoside, of which 102 (53.1%) had aminoglycoside doses that did not conform to national guidelines. Aminoglycoside-related adverse effects were suspected in 65 (33.9%) patients. Monitoring of aminoglycoside therapy was performed in only 17 (8.9%) patients, with no therapeutic drug monitoring (TDM), attributed mainly to knowledge and skill gaps and lack of resources. Out of the 28 recruited HCWs, 18 (64.3%) needed training in how to perform and interpret TDM results. Conclusions The practice of using and monitoring aminoglycosides was suboptimal, raising concerns around potential avoidable harm to patients. The identified gaps could form the basis for developing strategies to improve the future use of aminoglycosides, not only in Kenya but also in other countries with similar settings and resources.

Is Computer-Assisted Aminoglycoside Dosing Managed by a Pharmacist a Safety Tool of Pharmacotherapy?

This pilot prospective study verified the hypothesis that use of computer-assisted therapeutic drug monitoring of aminoglycosides by pharmacists leads to better safety therapeutic outcomes and cost avoidance than only concentration measurement and dose adjustments based on a physician’s experience. Two groups of patients were enrolled according to the technique of monitoring. Patients (Group 1, n=52) underwent monitoring by a pharmacist using pharmacokinetic software. In a control group (Group 2, n=11), plasma levels were measured but not interpreted by the pharmacist, only by physicians. No statistically significant differences were found between the groups in factors influenced by therapy. However, the results are not statistically significant but a comparison of the groups showed a clear trend towards safety and cost avoidance, thus supporting therapeutic drug monitoring. Safety limits were achieved in 76 % and 63 % of cases in Groups 1 and 2, respectively. More patients achieved both concentrations (peak and trough) with falling eGFR in Group 1. In present pilot study, the pharmacist improved the care of patients on aminoglycoside therapy. A larger study is needed to demonstrate statistically significantly improved safety and cost avoidance of aminoglycoside therapy monitoring by the pharmacist using pharmacokinetic software.

2222. Impact of Empiric Aminoglycoside Usage on Outcomes in Bacterial Pneumonia

Background Although aminoglycosides are recommended as part of empiric combination therapy in selected patients with healthcare-associated pneumonia, their efficacy and safety remains unclear. The objectives of this study were to evaluate the impact of empiric aminoglycoside treatment on microbiologic cure, recurrent pneumonia and death, and acute kidney injury (AKI) among hospitalized patients treated for pneumonia who were clinically cured. Methods This was a nested cohort study including 441 hospitalized subjects with confirmed bacterial pneumonia who achieved clinical cure. All subjects had positive respiratory cultures at the beginning of therapy and also had cultures obtained at the time of antibiotic completion. Subjects with the same pathogen present at both the beginning of and at the end of treatment were categorized as microbiologic failure and all others were categorized as microbiologic cure. Serum creatinine was measured at both the beginning and end of therapy, with an absolute increase in serum creatinine of 0.5 mg/L or greater defined as AKI. Composite outcomes of 30- and 90-day recurrent pneumonia or death following the clinical cure of the index pneumonia were captured. Patients who received empiric aminoglycoside therapy were compared with patients who did not receive aminoglycoside therapy. Results Of 441 included subjects, 14.5% (N = 64) received aminoglycoside therapy and 85.5% (N = 377) did not. The mean age was 54.7 years, with 70.5% male and 78.2% white. Characteristics of the two groups (including Charlson Comorbidity Indices and APACHE II scores) were similar. Rates of microbiologic cure, death/recurrent pneumonia at 30- and 90-days and AKI and were similar in both groups (table). In subgroup analyses restricted to different pathogen groups these associations remained unchanged. Conclusion Among hospitalized patients with pneumonia who were clinically cured, empiric aminoglycoside therapy was not associated with an increased likelihood of microbiologic cure, death or recurrent pneumonia or AKI. Disclosures All authors: No reported disclosures.

1551. Systemic Tobramycin Absorption Resulting from Antibiotic-Impregnated Cement Spacers for the Treatment of Prosthetic Joint Infection

Background Antibiotic-impregnated cement spacer (ACS) placement has been a cornerstone of two-stage surgical management of prosthetic hip and knee infection for decades. Utilized antibiotics have included aminoglycosides and vancomycin. Pharmacokinetic modeling studies have described peak systemic levels within the first 24–48 hours post-operatively, followed by rapid clearance. While this systemic exposure was previously felt insufficient to cause organ toxicity, a few studies have described antibiotic-induced nephrotoxicity. Methods We prospectively enrolled patients with prosthetic hip or knee infection, and subsequent ACS placement, containing vancomycin and tobramycin, from October 2017 to February 2019, at Allegheny General Hospital. Risk factors for post-operative nephrotoxicity, including patient comorbidities, receipt of potentially nephrotoxic medications, estimated creatinine clearance (CrCl), perioperative hypotension, total spacer tobramycin dosage, and post-operative day 1 (POD1) and 3 (POD3) serum tobramycin levels were recorded. Patients who had antibiotic cement spacer exchange, or had received systemic aminoglycoside therapy, were excluded. Results Thirteen patients were enrolled, comprising 4 hip and 9 knee ACS, with respective median (interquartile range (IQR)) tobramycin cement dosages of 3.8 (2.86–4.58) and 4.8 (4.8–9.6) grams. Tobramycin levels were measured at a median 16.5 and 60.7 hours on POD1 and POD3, respectively. Three hip and six knee ACS had respective, detectable POD1 median serum tobramycin levels of 0.6 (0.38–1.20) and 0.8 (0–0.8) μg/mL; three knees, but no hip ACS had detectable POD3 serum tobramycin levels. Six of the nine patients with detectable POD1 serum tobramycin levels had a CrCl of less than or equal to 65 mL/minute (figure), while each patient with detectable POD3 levels had a CrCl of less than 45 mL/minute. No significant changes in baseline CrCl were identified. A relationship between tobramycin cement dosage and detectable serum tobramycin levels was not observed. Conclusion Low baseline CrCl, but not the total tobramycin dosage or other nephrotoxicity risk factors, may be the single most reliable predictor of detectable postoperative systemic tobramycin levels in patients who have received hip or knee ACS. Disclosures All authors: No reported disclosures.