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1.
JAC Antimicrob Resist ; 5(2): dlad034, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36994231

ABSTRACT

Background: Fluoroquinolones are used for infection prevention in high-risk patients with haematological malignancies. Fluoroquinolones are active against many Gram-negative bacilli (GNB) but are less active against Gram-positive organisms. We evaluated the in vitro activity of delafloxacin and selected comparators against 560 bacterial pathogens isolated exclusively from patients with cancer. Methods: Antimicrobial susceptibility testing and time-kill studies were performed using CLSI-approved methodology and interpretive criteria for 350 Gram-positive organisms and 210 GNB that had been recently isolated from patients with cancer. Results: Delafloxacin was more active than ciprofloxacin and levofloxacin against Staphylococcus aureus and CoNS. Overall, 63% of staphylococcal isolates were susceptible to delafloxacin, 37% to ciprofloxacin and 39% to levofloxacin. Activity of delafloxacin against most Enterobacterales was similar to that of ciprofloxacin and levofloxacin. Escherichia coli and MDR Pseudomonas aeruginosa isolates had low susceptibility rates to the three tested fluoroquinolones. In time-kill studies delafloxacin and levofloxacin decreased the bacterial load to 3.0 log10 in 8 and 13 h, respectively, using 8 × MIC. Conclusions: Delafloxacin is more active than ciprofloxacin and levofloxacin against S. aureus but has substantial gaps in coverage against GNB. Resistance to all three fluoroquinolones could be high among leading GNB such as E. coli and P. aeruginosa, particularly in cancer centres where these agents are widely used as prophylactic agents.

2.
JAC Antimicrob Resist ; 5(2): dlad020, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36875177

ABSTRACT

Background: Bacterial infections are common in patients with cancer, and many bacteria have developed resistance to currently used antibiotics. Objectives: We evaluated the in vitro activity of eravacycline (a recently developed fluorocycline) and comparators against bacterial pathogens isolated from patients with cancer. Methods: Antimicrobial susceptibility testing was performed using CLSI-approved methodology and interpretive criteria for 255 Gram-positive and 310 Gram-negative bacteria. MIC and susceptibility percentage were calculated according to CLSI and FDA breakpoints when available. Results: Eravacycline had potent activity against most Gram-positive bacteria, including MRSA. Of 80 Gram-positive isolates with available breakpoints, 74 (92.5%) were susceptible to eravacycline. Eravacycline had potent activity against most Enterobacterales, including ESBL-producing organisms. Of 230 Gram-negative isolates with available breakpoints, 201 (87.4%) were susceptible to eravacycline. Eravacycline had the best activity among comparators against carbapenem-resistant Enterobacterales, with 83% susceptibility. Eravacycline was also active against many non-fermenting Gram-negative bacteria, with the lowest MIC90 value among comparators. Conclusions: Eravacycline was active against many clinically significant bacteria isolated from patients with cancer, including MRSA, carbapenem-resistant Enterobacterales, and non-fermenting Gram-negative bacilli. Eravacycline might play an important role in the treatment of bacterial infections in patients with cancer, and additional clinical evaluation is warranted.

3.
Open Forum Infect Dis ; 9(7): ofac240, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35854988

ABSTRACT

Background: Rising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSIs) in US cancer patients, it is unclear if current guidelines remain relevant. Methods: In a cross-sectional study, 14 US cancer centers prospectively identified BSIs in high-risk febrile neutropenic (FN) patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation. Results: Among 389 organisms causing BSI in 343 patients, there was an equal distribution of gram-negative (GN) and gram-positive (GP) bacteria, with variability across centers. Cefepime and piperacillin-tazobactam were the most commonly prescribed empirical antibiotics for FN, at 62% and 23%, respectively; a GP-directed agent was empirically included in nearly half of all FN episodes within the first 24 hours. Susceptibility to fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems was 49%, 84%, 88%, and 96%, respectively, among GN isolates. Critical illness (CrI), defined as a new requirement for mechanical ventilation, vasopressor, or death within 30 days, occurred in 15% and did not correlate with fluoroquinolone prophylaxis, organism type, initial antibiotics, or adequacy of coverage. Only severity of illness at presentation, signified by a Pitt bacteremia score ≥2, predicted for critical illness within 30 days. Mortality was 4% by day 7 and 10% overall. Conclusions: In accordance with US guidelines, cefepime or piperacillin-tazobactam remain effective agents or empirical treatment for high-risk cancer patients with FN who are stable at presentation, maintaining high GN pathogen susceptibility and yielding excellent outcomes.

4.
J Glob Antimicrob Resist ; 29: 1-6, 2022 06.
Article in English | MEDLINE | ID: mdl-35121163

ABSTRACT

OBJECTIVES: Gram-negative bacilli (GNB) are currently the predominant bacterial pathogens in patients with cancer. Many GNB have become problematic due to the widespread emergence of resistance. Imipenem/relebactam (IMI/REL) is a combination of the carbapenem imipenem with relebactam, a non-ß-lactam ß-lactamase inhibitor. It is active against most pathogenic GNB including many that are resistant to other agents. We compared its in vitro activity to six other agents against 490 GNB recovered exclusively from patients with cancer because such data are scarce. METHODS: Clinical and Laboratory Standards Institute (CLSI) microbroth dilution methods were used for susceptibility testing. Whole genome sequencing (Illumina MiSeq) was performed on 30 selected isolates. RESULTS: IMI/REL was active against 98% of Enterobacterales and 87% of non-Enterobacterales isolates (excluding Stenotrophomonas maltophilia). It had potent activity against extended spectrum ß-lactamase-producing Escherichia coli, Klebsiella pneumoniae, and other Enterobacterales (Enterobacter cloacae, Citrobacter Spp., and Serratia Spp.) and moderate activity against carbapenem-resistant Enterobacterales. IMI/REL had potent activity against Achromobacter Spp., non-multidrug resistant Pseudomonas aeruginosa, and Sphingomonas paucimobilis and moderate activity against multidrug resistant P. aeruginosa. Overall, IMI/REL was associated with the lowest number of nonsusceptible isolates compared with six other agents (imipenem, meropenem, cefepime, piperacillin/tazobactam, amikacin, and tigecycline) commonly used in patients with cancer. Whole genome sequencing performed on 30 resistant isolates (10 each of E. coli, K. pneumonia, and P. aeruginosa) did not reveal any predominant mechanism of resistance to IMI/REL. CONCLUSION: Its in vitro activity indicates that IMI/REL might have a role to play in the treatment of Gram-negative infections in patients with cancer.


Subject(s)
Imipenem , Neoplasms , Anti-Bacterial Agents/pharmacology , Carbapenems , Escherichia coli , Gram-Negative Bacteria , Humans , Imipenem/pharmacology , Microbial Sensitivity Tests , Pseudomonas aeruginosa
5.
Infect Dis Ther ; 11(2): 683-694, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35175509

ABSTRACT

Carbapenem-resistant Acinetobacter baumannii (CRAB) causes colonization and infection predominantly in hospitalized patients. Distinction between the two is a challenge. When CRAB is isolated from a non-sterile site (soft tissue, respiratory samples, etc.), it probably represents colonization unless clear signs of infection (fever, elevated white blood count, elevated inflammatory markers and abnormal imaging) are present. Treatment is warranted only for true infections. In normally sterile sites (blood, cerebrospinal fluid) the presence of indwelling medical devices (catheters, stents) should be considered when evaluating positive cultures. In the absence of such devices, the isolate represents an infection and should be treated. If an indwelling device is present and there are no signs of active infection, the device should be replaced if possible, and no treatment is required. If there are signs of an active infection the device should be removed or replaced, and treatment should be administered. Current treatments options and clinical data are limited. No agent or combination regimen has been shown to be superior to any other in randomized clinical trials. Ampicillin-sulbactam appears to have the best evidence for initial use. This is probably due to its ability to saturate penicillin-binding proteins 1 and 3 when given in high dose. Tigecycline when used should be given in high dose as well. Polymyxins are a treatment option but are difficult to dose correctly and have significant side effects. Newer treatment options such as eravacycline and cefiderocol have potential; however, currently there are not enough data to support their use as single agents. Combination therapy appears to be the best treatment option and should always include high-dose ampicillin-sulbactam combined with another active agent such as high-dose tigecycline, polymyxins, etc. These infections require a high complexity of skill, and an infectious disease specialist should be involved in the management of these patients.

6.
Article in English | MEDLINE | ID: mdl-32071053

ABSTRACT

Cefiderocol inhibited 97.5% of 478 Gram-negative isolates from cancer patients at ≤4 mg/liter. It had potent activity against extended-spectrum ß-lactamase-positive Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae (CRE), and nonfermenting Gram-negative bacilli, including Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter species isolates. Amikacin, ceftazidime-avibactam, and meropenem had appreciable activity against non-CRE Enterobacteriaceae No comparators were active against multidrug-resistant P. aeruginosa isolates. Only trimethoprim-sulfamethoxazole had appreciable activity against S. maltophilia isolates. Overall, cefiderocol was associated with the lowest level of resistance.


Subject(s)
Amikacin/pharmacology , Anti-Bacterial Agents/pharmacology , Azabicyclo Compounds/pharmacology , Ceftazidime/pharmacology , Cephalosporins/pharmacology , Gram-Negative Bacteria/drug effects , Meropenem/pharmacology , Acinetobacter/drug effects , Acinetobacter/isolation & purification , Carbapenem-Resistant Enterobacteriaceae/drug effects , Carbapenem-Resistant Enterobacteriaceae/isolation & purification , Drug Combinations , Gram-Negative Bacteria/isolation & purification , Humans , Microbial Sensitivity Tests , Neoplasms/pathology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/isolation & purification , Stenotrophomonas maltophilia/drug effects , Stenotrophomonas maltophilia/isolation & purification , Cefiderocol
7.
Infect Dis (Lond) ; 52(5): 330-335, 2020 05.
Article in English | MEDLINE | ID: mdl-31983251

ABSTRACT

Background: HBV (hepatitis B virus) vaccination in first year of life is recommended to prevent infection. Observational studies have suggested that vaccination at birth provides protection for 90% of the population for 30 years. Data on response to booster doses and long-term protection are lacking.Methods: We compared HBV antibody levels of healthcare students who were immunized for HBV with a primary series during their first year of life (primary) to students who were immunized with a primary series and received an additional dose at age 18 (boosted) four years earlier. Antibody titres ≥10 mIU/mL were considered adequate. Those that were inadequate received another dose and were reassessed.Results: We assessed 381 students, 80.1% were primary and 19.9% boosted. A significantly higher percentage of students in the boosted group had antibody titre levels ≥10 mIU/mL compared to primary group (88.1% vs. 41.3%, p < .001). Of 179 students in the primary group with inadequate antibody levels, 134 received a booster dose and 126 of them (94%) developed anti-HBs levels ≥10 mIU/mL. Of 9 students with inadequate levels in the boosted group, 8 received another booster dose and all developed adequate levels.Conclusions: Primary vaccination against HBV at birth does not necessarily provide lifelong adequate antibody levels. Boosting at 18 years reinforces antibody levels for at least four more years. Current guidelines recommend testing and boosting all medical personal. Based on our study, it may be prudent to extend this practice to all individuals who are at higher risk.


Subject(s)
Hepatitis B Antibodies/blood , Hepatitis B Vaccines/administration & dosage , Hepatitis B virus/immunology , Hepatitis B/prevention & control , Adolescent , Female , Health Personnel , Hepatitis B Surface Antigens , Humans , Immunologic Memory , Male , Students , Vaccination , Young Adult
8.
Infect Control Hosp Epidemiol ; 40(8): 897-903, 2019 08.
Article in English | MEDLINE | ID: mdl-31190679

ABSTRACT

OBJECTIVE: To assess the impact of incorporating early rapid influenza diagnosis on antimicrobial usage, nosocomial influenza transmission, length of stay, and occupancy rates among hospitalized patients. SETTING: A 1,100 bed tertiary-care hospital in southern Israel. METHODS: We implemented early rapid detection of influenza with immediate communication of results. Using Orion methods, we compared the 2017-2018 influenza season to the prior season in our hospital and to the 2017-2018 occupancy rates at other Israeli hospitals. RESULTS: During the intervention season, 5,006 patients were admitted; 1,824 were tested for influenza, of whom 437 (23.9%) were positive. In the previous season, 4,825 patients were admitted; 1,225 were tested and 288 (23.5%) were positive. Time from admission to test report decreased from 35.5 to 18.4 hours (P < .001). Early discharge rates significantly increased, from 21.5% to 41.6% at 36 hours, from 37.2% to 54.5% at 48 hours, and from 66% to 73.2% at 72 hours. No increase in repeat ER visits, readmission, or mortality rates was observed. Hospital occupancy decreased by 10% compared to the previous year and was 26% lower than the national rate. Hospital-acquired influenza cases were reduced from 37 (11.4%) to 12 (2.7%) (P < .001). Antibiotic usage was reduced both before and after notification of test results by 16% and 12%, respectively. CONCLUSIONS: Implementing this intervention led to earlier discharge of patients, lower occupancy in medical wards, reduced antibiotic administration, and fewer hospital-acquired influenza events. This strategy is useful for optimizing hospital resources, and its implementation should be considered for upcoming influenza seasons.


Subject(s)
Cross Infection , Hospitalization , Influenza, Human/diagnosis , Length of Stay , Reagent Kits, Diagnostic , Aged , Aged, 80 and over , Female , Humans , Israel , Male , Middle Aged , Program Evaluation , Retrospective Studies
9.
Article in English | MEDLINE | ID: mdl-31010862

ABSTRACT

Bloodstream infection (BSI) organisms were consecutively collected from >200 medical centers in 45 nations between 1997 and 2016. Species identification and susceptibility testing followed Clinical and Laboratory Standards Institute broth microdilution methods at a central laboratory. Clinical data and isolates from 264,901 BSI episodes were collected. The most common pathogen overall was Staphylococcus aureus (20.7%), followed by Escherichia coli (20.5%), Klebsiella pneumoniae (7.7%), Pseudomonas aeruginosa (5.3%), and Enterococcus faecalis (5.2%). S. aureus was the most frequently isolated pathogen overall in the 1997-to-2004 period, but E. coli was the most common after 2005. Pathogen frequency varied by geographic region, hospital-onset or community-onset status, and patient age. The prevalence of S. aureus isolates resistant to oxacillin (ORSA) increased until 2005 to 2008 and then declined among hospital-onset and community-acquired BSI in all regions. The prevalence of vancomycin-resistant enterococci (VRE) was stable after 2012 (16.4% overall). Daptomycin resistance among S. aureus and enterococci (DRE) remained rare (<0.1%). In contrast, the prevalence of multidrug-resistant (MDR) Enterobacteriaceae increased from 6.2% in 1997 to 2000 to 15.8% in 2013 to 2016. MDR rates were highest among nonfermentative Gram-negative bacilli (GNB), and colistin was the only agent with predictable activity against Acinetobacter baumannii-Acinetobacter calcoaceticus complex (97% susceptible). In conclusion, S. aureus and E. coli were the predominant causes of BSI worldwide during this 20-year surveillance period. Important resistant phenotypes among Gram-positive pathogens (MRSA, VRE, or DRE) were stable or declining, whereas the prevalence of MDR-GNB increased continuously during the monitored period. MDR-GNB represent the greatest therapeutic challenge among common bacterial BSI pathogens.


Subject(s)
Bacteremia/epidemiology , Bacteremia/microbiology , Acinetobacter Infections/epidemiology , Acinetobacter Infections/microbiology , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/isolation & purification , Anti-Bacterial Agents/pharmacology , Community-Acquired Infections/epidemiology , Community-Acquired Infections/microbiology , Drug Resistance, Bacterial/drug effects , Enterococcus faecalis/drug effects , Enterococcus faecalis/isolation & purification , Europe/epidemiology , Gram-Positive Bacterial Infections/epidemiology , Gram-Positive Bacterial Infections/microbiology , Humans , Klebsiella Infections/epidemiology , Klebsiella Infections/microbiology , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/isolation & purification , Latin America/epidemiology , Microbial Sensitivity Tests , Pseudomonas Infections/epidemiology , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/isolation & purification , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology , Staphylococcus aureus/drug effects , Staphylococcus aureus/isolation & purification
11.
Plast Reconstr Surg Glob Open ; 7(7): e2342, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31942364

ABSTRACT

Several steps to reduce the rate of postoperative surgical site infections (SSIs) have been implemented. The use of prophylactic antimicrobials targeting patient's microbial flora has been associated with a decrease in postoperative infections. We evaluated the relationship between perioperative antimicrobials, baseline microbial flora, and occurrence of SSIs. METHODS: We prospectively enrolled 241 patients scheduled to receive a postmastectomy implant-based reconstructive procedure between September 2015 and January 2018. Axillary swab cultures were obtained preoperatively, and all recovered bacteria were identified. Surgeons were blinded to these results. The use of prophylactic perioperative antimicrobials was defined as concordant if the baseline axillary flora were susceptible to the given antibiotic and discordant if not. As Staphylococcus species are the most common pathogen causative for breast implant-related infections, patients colonized with these organisms were analyzed in detail. All patients were followed up for at least 6 months postoperatively and evaluated for SSIs. RESULTS: A total of 238 patients (99%) received both perioperative and postoperative oral antimicrobials. The most common preoperative staphylococci axillary flora recovered were methicillin-sensitive coagulase-negative Staphylococcus (67%), methicillin-resistant coagulase-negative Staphylococcus (35%), with only 1 case of methicillin-sensitive Staphylococcus aureus (0.4%). Thirty-three patients (14%) developed an SSI. Of those with a positive Staphylococcus culture, only 54% received a concordant antimicrobial regimen, but this was not associated with an increased risk for infection (P > 0.72). CONCLUSIONS: The use of perioperative antimicrobials whether concordant or discordant with the preoperative axillary microbial flora, specifically Staphylococci species, did not provide a significant impact on the risk of SSI.

12.
Infection ; 47(2): 239-245, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30406481

ABSTRACT

PURPOSE: Percutaneous nephrostomy (PCN) catheters are mainly indicated for urinary tract obstructions. Unfortunately, the rate for infection and recurrence remains elevated. Our objective was to identify the risk factors leading to recurrent PCN-related infections (PCNI) in cancer patients. METHODS: We retrospectively reviewed 571 patients who underwent initial PCN catheter placement at our institution. Of these, we identified patients with a definite PCNI and catheter exchange, with a minimum 30-day follow-up. We defined PCNI as presence of a urine culture positive for bacteria (≥ 104 CFU/mL) plus symptoms of urinary tract infection. A PCNI was considered recurrent if the same organism was isolated. Antibiotics were considered concordant if they were active against all identified organisms. RESULTS: A total of 81 patients (14%) developed an initial PCNI. Of 47 patients with 30-day follow-up, 10 patients (21%) were identified as having a recurrent PCNI. In terms of demographic characteristics, clinical manifestations, and microbiological data, there was no statistically significant difference between the recurrent and non-recurrent groups. However, in multivariate logistic regression analysis, two factors were independently associated with a decrease in recurrent PCNI: concordant antibiotic use (OR 0.04; p = 0.008) and PCN catheter exchange within 4 days of infection (OR 0.1; p = 0.048). CONCLUSIONS: To decrease the high rate of recurrent infections, associated costs, and potential delay in further chemotherapy, we recommend that once antimicrobial susceptibility test results are available and the patient is known to be receiving concordant antimicrobials, clinicians proceed with immediate PCN catheter exchange, ideally within the first 4 days of the infection.


Subject(s)
Catheter-Related Infections/epidemiology , Nephrostomy, Percutaneous/statistics & numerical data , Urinary Catheterization/adverse effects , Urinary Tract Infections/epidemiology , Adult , Aged , Aged, 80 and over , Catheter-Related Infections/etiology , Female , Humans , Inpatients/statistics & numerical data , Male , Middle Aged , Neoplasms/therapy , Recurrence , Retrospective Studies , Risk Factors , Texas/epidemiology , Urinary Tract Infections/etiology , Young Adult
13.
J Infect ; 78(1): 48-53, 2019 01.
Article in English | MEDLINE | ID: mdl-30048653

ABSTRACT

OBJECTIVE: To investigate the clinical manifestations, microbiological data, and outcomes of Bordetella bronchiseptica (Bb) infections in patients with cancer. METHODS: Review of electronic medical records of 24 patients with Bb infection, from 2000 to 2013. An infection was considered to be associated with Bb if both clinical manifestations plus microbial growth from infected sites were present. RESULTS: Ten patients (42%) had a monomicrobial infection, whereas multiple pathogens in addition to Bb were isolated from the rest (14 patients, 58%). The most frequent sites of infection were the respiratory tract (18 patients, 75 %) and bloodstream (17%). The most frequently associated conditions were lymphopenia (71%), tobacco use (42%), and chemotherapeutic or immunosuppressive agents (33% each). Animal exposure was established in four patients. Overall, the response rate to treatment was 100% for monomicrobial and 79% for polymicrobial infections, respectively. CONCLUSIONS: Bb is an uncommon pathogen even in immunosuppressed patients. Predominant sites of infection are the respiratory tract and bloodstream. Bb should be considered pathogenic in immunocompromised hosts, particularly with history of zoonotic exposure, even if accompanied by co-pathogens. Therefore, contact with potential animal sources should be minimized. The infection ranges from mild to severe and has no specific clinical or radiographic manifestations.


Subject(s)
Cough/microbiology , Immunocompromised Host , Neoplasms/complications , Respiratory Tract Infections/microbiology , Adult , Aged , Bordetella Infections/microbiology , Bordetella bronchiseptica/isolation & purification , Bordetella bronchiseptica/pathogenicity , Coinfection , Female , Humans , Male , Middle Aged
14.
J Clin Oncol ; 36(30): 3043-3054, 2018 10 20.
Article in English | MEDLINE | ID: mdl-30179565

ABSTRACT

PURPOSE: To provide an updated joint ASCO/Infectious Diseases Society of America (IDSA) guideline on antimicrobial prophylaxis for adult patients with immunosuppression associated with cancer and its treatment. METHODS: ASCO and IDSA convened an update Expert Panel and conducted a systematic review of relevant studies from May 2011 to November 2016. The guideline recommendations were based on the review of evidence by the Expert Panel. RESULTS: Six new or updated meta-analyses and six new primary studies were added to the updated systematic review. RECOMMENDATIONS: Antibacterial and antifungal prophylaxis is recommended for patients who are at high risk of infection, including patients who are expected to have profound, protracted neutropenia, which is defined as < 100 neutrophils/µL for > 7 days or other risk factors. Herpes simplex virus-seropositive patients undergoing allogeneic hematopoietic stem-cell transplantation or leukemia induction therapy should receive nucleoside analog-based antiviral prophylaxis, such as acyclovir. Pneumocystis jirovecii prophylaxis is recommended for patients receiving chemotherapy regimens that are associated with a > 3.5% risk for pneumonia as a result of this organism (eg, those with ≥ 20 mg prednisone equivalents daily for ≥ 1 month or on the basis of purine analog usage). Treatment with a nucleoside reverse transcription inhibitor (eg, entecavir or tenofovir) is recommended for patients at high risk of hepatitis B virus reactivation. Recommendations for vaccination and avoidance of prolonged contact with environments that have high concentrations of airborne fungal spores are also provided within the updated guideline. Additional information is available at www.asco.org/supportive-care-guidelines .


Subject(s)
Anti-Infective Agents/therapeutic use , Immunocompromised Host , Infection Control/methods , Infections/immunology , Humans , Neoplasms/immunology , Neoplasms/therapy
15.
Diagn Microbiol Infect Dis ; 91(4): 351-353, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29661529

ABSTRACT

A total of 248 Gram-positive isolates from cancer patients were tested for in-vitro susceptibility to tedizolid and 3 comparator agents using CLSI broth microdilution methodology. Tedizolid inhibited 97% of isolates at ≤0.5µg/ml. It was active against all Gram-positive species and consistently had 8 fold lower MICs than linezolid, although based on % susceptibility using CLSI breakpoints, most isolates were also susceptible to the comparators. Tedizolid was active against MRSA isolates with vancomycin MICs of ≥1.0µg/ml.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial , Gram-Positive Bacteria/drug effects , Gram-Positive Bacterial Infections/microbiology , Oxazolidinones/pharmacology , Tetrazoles/pharmacology , Daptomycin/pharmacology , Humans , Linezolid/pharmacology , Microbial Sensitivity Tests , Microbial Viability/drug effects , Vancomycin/pharmacology
16.
J Clin Oncol ; 36(14): 1443-1453, 2018 05 10.
Article in English | MEDLINE | ID: mdl-29461916

ABSTRACT

Purpose To provide an updated joint ASCO/Infectious Diseases Society of American (IDSA) guideline on outpatient management of fever and neutropenia in patients with cancer. Methods ASCO and IDSA convened an Update Expert Panel and conducted a systematic review of relevant studies. The guideline recommendations were based on the review of evidence by the Expert Panel. Results Six new or updated meta-analyses and six new primary studies were added to the updated systematic review. Recommendation Clinical judgment is recommended when determining which patients are candidates for outpatient management, using clinical criteria or a validated tool such as the Multinational Association of Support Care in Cancer risk index. In addition, psychosocial and logistic considerations are outlined within the guideline. The panel continued to endorse consensus recommendations from the previous version of this guideline that patients with febrile neutropenia receive initial doses of empirical antibacterial therapy within 1 hour of triage and be monitored for ≥ 4 hours before discharge. An oral fluoroquinolone plus amoxicillin/clavulanate (or clindamycin, if penicillin allergic) is recommended as empirical outpatient therapy, unless fluoroquinolone prophylaxis was used before fever developed. Patients who do not defervesce after 2 to 3 days of an initial, empirical, broad-spectrum antibiotic regimen should be re-evaluated and considered as candidates for inpatient treatment. Additional information is available at www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki .


Subject(s)
Ambulatory Care/methods , Fever/drug therapy , Neoplasms/drug therapy , Neutropenia/drug therapy , Adult , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Antifungal Agents/therapeutic use , Antineoplastic Agents/adverse effects , Bacterial Infections/chemically induced , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , Fever/chemically induced , Humans , Mycoses/chemically induced , Mycoses/drug therapy , Mycoses/microbiology , Neutropenia/chemically induced
17.
Infect Dis Ther ; 7(1): 29-38, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29392577

ABSTRACT

Published literature on post-obstructive pneumonia is difficult to find and consists mainly of case reports or small case series. This entity is encountered most often in patients with advanced lung malignancy but is also occasionally seen in patients with community-acquired pneumonia (CAP). There are substantial differences in the manifestations, treatment, and outcomes of post-obstructive pneumonia in these two settings. When obstruction is present in patients with CAP, it is almost always secondary to an underlying pulmonary malignancy. In fact, the observation of an obstructive component in patients with CAP leads to the detection of primary or metastatic lung cancer in more than 50% of such individuals. Post-obstructive pneumonia in patients with advanced lung malignancy is far more common (~ 50% of patients) and is associated with substantial morbidity and mortality. The management of these patients is very challenging and involves multiple disciplines including medical oncology, pulmonary medicine, infectious diseases, intervention radiology, surgery, and intensive care teams. The administration of broad-spectrum antibiotic regimens is generally required. Refractory or recurrent infections despite the administration of appropriate antimicrobial therapy are the norm. Frequent and prolonged antibiotic administration leads to the development of resistant microflora. Complications such as lung abscess, empyema, and local fistula formation develop often. Relief of obstruction generally produces only temporary symptomatic improvement.

18.
Int J Antimicrob Agents ; 49(4): 416-421, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28257904

ABSTRACT

Bacterial infections are common in cancer patients. Ceftaroline (CFT) is a broad-spectrum cephalosporin with activity against most Gram-positive organisms (GPOs) and many Gram-negative organisms. In this study, the in vitro activity of CFT was compared with vancomycin (VAN), daptomycin (DAP), linezolid (LZD), trimethoprim/sulphamethoxazole (SXT) and tigecycline (TIG) against bacteria (predominantly blood culture isolates) isolated from cancer patients in 2014 and 2015. CFT was active against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), methicillin-susceptible coagulase-negative staphylococci (MS-CoNS) and methicillin-resistant coagulase-negative staphylococci (MR-CoNS) with MIC90 values (minimum inhibitory concentration that inhibited 90% of the isolates) of 0.25, 2.0, 0.12 and 0.5 mg/L, respectively. MIC90 values for other GPOs were: Bacillus spp., >8.0 mg/L; Corynebacterium spp., 2.0 mg/L; Micrococcus spp., <0.06 mg/L; viridans group streptococci, 0.5 mg/L; Streptococcus pneumoniae, 0.25 mg/L; and Streptococcus spp., <0.06 mg/L. Among the comparator agents, VAN, DAP, TIG and LZD were active against the majority of GPOs tested. CFT also had moderate activity against common extended-spectrum ß-lactamase (ESBL)-negative Gram-negative bacilli such as Enterobacter cloacae, Escherichia coli, Klebsiella spp., Proteus mirabilis and Serratia spp.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Infections/microbiology , Cephalosporins/pharmacology , Gram-Negative Bacteria/drug effects , Neoplasms/complications , Gram-Negative Bacteria/isolation & purification , Humans , Microbial Sensitivity Tests , Ceftaroline
19.
Infect Dis Ther ; 6(1): 69-83, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28160269

ABSTRACT

Solid tumors are much more common than hematologic malignancies. Although severe and prolonged neutropenia is uncommon, several factors increase the risk of infection in patients with solid tumors, and the presence of multiple risk factors in the same patient is not uncommon. These include obstruction (most often caused by progression of the tumor), disruption of natural anatomic barriers such as the skin and mucosal surfaces, and treatment-related factors such as chemotherapy, radiation, diagnostic and/or therapeutic surgical procedures, and the increasing use of medical devices such as various catheters, stents, and prostheses. Common sites of infection include the skin and skin structures (including surgical site infections), the bloodstream (including infections associated with central venous catheters), the lungs, the hepato-biliary and intestinal tracts, and the urinary tract, and include distinct clinical syndromes such as post-obstructive pneumonia, obstructive uropathy, and neutropenic enterocolitis. The epidemiology of most of these infections is changing with resistant organisms [MRSA, Pseudomonas aeruginosa, extended spectrum beta-lactamase (ESBL)-producing organisms] being isolated more often than in the past. Polymicrobial infections now predominate when deep tissue sites are involved. Conservative management of most of these infections (antibiotics, fluid and electrolyte replacement, bowel rest when needed) is generally effective, with surgical intervention being reserved for the drainage of deep abscesses, or to deal with complications such as intestinal obstruction or hemorrhage. Infected prostheses often need to be removed. Reactivation of certain viral infections (HBV, HCV, and occasionally CMV) has become an important issue, and screening, prevention and treatment strategies are being developed. Infection prevention, infection control, and antimicrobial stewardship are important strategies in the overall management of infections in patients with solid tumors. Occasionally, infections mimic solid tumors and cause diagnostic and therapeutic challenges.

20.
Article in English | MEDLINE | ID: mdl-28115350

ABSTRACT

A total of 521 unique clinical isolates from cancer patients with primarily (>90%) bloodstream infections were tested for susceptibility to ceftazidime-avibactam and comparators using broth microdilution methods. Ceftazidime-avibactam inhibited 97.8% of all Enterobacteriaceae (n = 321) at the susceptibility breakpoint of ≤8/4 µg/ml (there were 7 nonsusceptible strains). It was also active against Pseudomonas aeruginosa (91.7% isolates susceptible, n = 121), including many isolates not susceptible to meropenem, cefepime, ceftazidime, piperacillin-tazobactam, or other comparators.


Subject(s)
Anti-Bacterial Agents/pharmacology , Azabicyclo Compounds/pharmacology , Ceftazidime/pharmacology , Drug Resistance, Multiple, Bacterial , Enterobacteriaceae/drug effects , Pseudomonas aeruginosa/drug effects , Cefepime , Cephalosporins/pharmacology , Drug Combinations , Enterobacteriaceae/growth & development , Enterobacteriaceae/isolation & purification , Enterobacteriaceae Infections/complications , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/microbiology , Humans , Meropenem , Microbial Sensitivity Tests , Neoplasms/complications , Neoplasms/drug therapy , Neoplasms/microbiology , Opportunistic Infections/complications , Opportunistic Infections/drug therapy , Opportunistic Infections/microbiology , Penicillanic Acid/analogs & derivatives , Penicillanic Acid/pharmacology , Piperacillin/pharmacology , Piperacillin, Tazobactam Drug Combination , Pseudomonas Infections/complications , Pseudomonas Infections/drug therapy , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/growth & development , Pseudomonas aeruginosa/isolation & purification , Thienamycins/pharmacology
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