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1.
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
2.
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
3.
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
4.
Clin Infect Dis ; 63(7): 954-958, 2016 10 01.
Article in English | MEDLINE | ID: mdl-27313265

ABSTRACT

Resistance to the novel ß-lactam/ß-lactamase inhibitor combination ceftazidime-avibactam (CAZ-AVI) among carbapenem-resistant Enterobacteriaceae (CRE) has infrequently been reported in the United States. We report unexpectedly high rates of resistance to CAZ-AVI in CRE bloodstream isolates at our institution associated with the nonoutbreak spread of New Delhi metallo-ß-lactamase in diverse Enterobacteriaceae species.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Azabicyclo Compounds/therapeutic use , Bacteremia , Ceftazidime/therapeutic use , Enterobacteriaceae Infections , Enterobacteriaceae , Adult , Aged , Anti-Bacterial Agents/pharmacology , Azabicyclo Compounds/pharmacology , Bacteremia/drug therapy , Bacteremia/epidemiology , Bacteremia/microbiology , Cancer Care Facilities , Ceftazidime/pharmacology , Child, Preschool , Drug Combinations , Drug Resistance, Bacterial , Enterobacteriaceae/drug effects , Enterobacteriaceae/enzymology , Enterobacteriaceae/genetics , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae Infections/microbiology , Female , Humans , Male , Middle Aged , Young Adult , beta-Lactamases
5.
Infection ; 43(5): 545-50, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25929421

ABSTRACT

PURPOSE: Ertapenem is being increasingly utilized in cancer patients, but published data regarding its usage are limited. Our objective was to describe the various indications for ertapenem therapy and its safety and efficacy in cancer patients. METHODS: We conducted a retrospective cohort study of cancer patients who received monotherapy with ertapenem for at least 72 h, between January 2007 and February 2013. RESULTS: Among 97 unique patients who received ertapenem monotherapy, the most common indications were: (1) To facilitate discharge from the hospital of stable patients still requiring antimicrobial therapy (46 %). (2) Primary therapy of various documented infections (bacteremia, pneumonia, urinary tract infection, skin and skin structure infection) with ertapenem (28 %). (3) De-escalation from a different broad-spectrum agent or regimen to ertapenem within the hospital setting in patients not ready for discharge (25 %). The median age of the 97 patients studied was 59 years (range 9-87 years) with 52 % being men. Most patients had underlying hematologic malignancies (54 %), and 7 % were recipients of hematopoietic stem cell transplantation. Twenty-nine patients (30 %) were neutropenic, 26 % were diabetic, and 6 % had chronic lung disease. Primary ertapenem monotherapy was successful in all patients, de-escalation in 95.8 % of patients, and the strategy of discharge on outpatient therapy with ertapenem in 95.6 % of patients. Patients failing de-escalation or early discharge responded to alternative regimens. We documented no significant ertapenem associated toxicity or adverse events. CONCLUSIONS: Ertapenem appears to be safe and effective for several indications in cancer patients.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Drug Utilization , Neoplasms/complications , Neutropenia/etiology , beta-Lactams/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/adverse effects , Child , Ertapenem , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult , beta-Lactams/adverse effects
6.
JAAPA ; 28(7): 52-4, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26107798

ABSTRACT

Middle East respiratory syndrome is an infection caused by a novel coronavirus. The primary source of the virus is infected camels in several countries in the Arabian peninsula. The infection is acquired by coming into contact with infected animals, animal products, or with patients who have the syndrome. Mortality for this syndrome is 30% to 40%, and treatment is supportive because no antiviral therapy exists.


Subject(s)
Coronavirus Infections , Animals , Camelus , Coronavirus , Coronavirus Infections/therapy , Coronavirus Infections/transmission , Humans , Male , Middle Aged , Middle East , Saudi Arabia , Travel
7.
Clin Infect Dis ; 59(2): 223-30, 2014 Jul 15.
Article in English | MEDLINE | ID: mdl-24755857

ABSTRACT

BACKGROUND: Concern for serious infection due to ß-lactam-resistant viridans group streptococci (VGS) is a major factor driving empiric use of an anti-gram-positive antimicrobial in patients with febrile neutropenia. We sought to develop and validate a prediction model for the presence of ß-lactam resistance in VGS causing bloodstream infection (BSI) in neutropenic patients. METHODS: Data from 569 unique cases of VGS BSI in neutropenic patients from 2000 to 2010 at the MD Anderson Cancer Center were used to develop the clinical prediction model. Validation was done using 163 cases from 2011 to 2013. In vitro activity of ß-lactam agents was determined for 2011-2013 VGS bloodstream isolates. RESULTS: In vitro resistance to ß-lactam agents commonly used in the empiric treatment of febrile neutropenia was observed only for VGS isolates with a penicillin minimum inhibitory concentration (MIC) of ≥ 2 µg/mL. One hundred twenty-nine of 732 patients (17%) were infected with VGS strains with a penicillin MIC ≥ 2 µg/mL. For the derivation and validation cohorts, 98% of patients infected by VGS with a penicillin MIC of ≥ 2 µg/mL had at least 1 of the following risk factors: current use of a ß-lactam as antimicrobial prophylaxis, receipt of a ß-lactam antimicrobial in the previous 30 days, or nosocomial VGS BSI onset. Limiting empiric anti-gram-positive therapy to neutropenic patients having at least 1 of these 3 risk factors would have reduced such use by 42%. CONCLUSIONS: Simple clinical criteria can assist with targeting of anti-gram-positive therapy to febrile neutropenic patients at risk of serious ß-lactam-resistant VGS infection.


Subject(s)
Bacteremia/microbiology , Decision Support Techniques , Neoplasms/complications , Neutropenia/complications , Streptococcal Infections/microbiology , Viridans Streptococci/drug effects , beta-Lactam Resistance , Adult , Aged , Cohort Studies , Female , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Prospective Studies , Retrospective Studies , Viridans Streptococci/isolation & purification
8.
Ann Surg Oncol ; 21(2): 513-9, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24114052

ABSTRACT

BACKGROUND: To evaluate the role of ertapenem versus other standard antibiotic prophylaxis in patients with cancer undergoing intra-abdominal surgery. METHODS: Our study was a retrospective cohort study consisting 615 patients who underwent intra-abdominal surgery at our institution between January 2007 and December 2010. The groups were divided among patients who received ertapenem as perioperative prophylaxis (ertapenem group) and patients who received other antibiotics (nonertapenem group). Groups were similar with respect to age, gender, and type of surgery. RESULTS: A total of 315 patients underwent colorectal and 300 noncolorectal surgeries. In a multivariate logistic regression model, the main factors associated with risk of surgical site infections (SSI) were as follows: antibiotics within 3 months of surgery (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.04-1.54; p = 0.05), prior hospitalization within 1 year (OR 1.21, 95% CI 1.02-1.43; p = 0.05), diabetes mellitus (OR 2.1, 95% CI 1.7-3.4; p = 0.04), and perioperative prophylaxis other than ertapenem (OR 1.7, 95% CI 1.2-2.3; p = 0.04). Notably, patients who underwent colorectal surgery and received ertapenem had a lower rate of SSI (4% ertapenem vs. 13% nonertapenem, p = 0.01), whereas the frequency of infections was not different in patients who underwent other intra-abdominal surgery whether they received ertapenem or not. CONCLUSIONS: The use of ertapenem for perioperative prophylaxis in patients with colorectal surgery was associated with lower rates of SSI, while there was no difference in rates of infection in other intra-abdominal surgery.


Subject(s)
Abdominal Neoplasms/surgery , Anti-Bacterial Agents/therapeutic use , Postoperative Complications/prevention & control , Surgical Wound Infection/drug therapy , beta-Lactams/therapeutic use , Abdominal Neoplasms/complications , Abdominal Neoplasms/pathology , Adult , Aged , Antibiotic Prophylaxis , Ertapenem , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Perioperative Care , Postoperative Complications/etiology , Prognosis , Retrospective Studies , Risk Factors , Surgical Wound Infection/etiology
9.
Cancer Treat Res ; 161: 181-202, 2014.
Article in English | MEDLINE | ID: mdl-24706225

ABSTRACT

Neutropenia remains the predominant predisposing factor for infection in most cancer patients. Bacterial and fungal infections are common in this setting. Not all neutropenic patients have the same risk of developing severe infection or serious medical complications. Although all patients with neutropenia and fever should receive prompt, empiric antibiotic therapy, low-risk patients can be effectively managed without hospitalization-often with the administration of oral antibiotics. Other patients need hospital-based therapy. The emergence of resistant microorganisms has become a significant problem in neutropenic patients. Frequent epidemiologic surveys to detect the emergence of resistant organisms are recommended. Antibiotic stewardship and Infection Control Programs are important tools in combating resistant organisms.


Subject(s)
Bacteremia/etiology , Fever/complications , Fungemia/etiology , Neutropenia/complications , Anti-Infective Agents/therapeutic use , Bacteremia/drug therapy , Drug Resistance, Bacterial , Drug Resistance, Fungal , Fungemia/drug therapy , Humans , Risk Factors
10.
Infection ; 42(1): 5-13, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23975584

ABSTRACT

Despite advancements in the treatment and supportive care of patients with malignant disorders, neutropenia remains the major side effect of most antineoplastic regimens. Infections occur frequently in neutropenic patients and are associated with considerable morbidity and mortality. The spectrum of infection continues to change, and is influenced by various factors including local epidemiology, the use of chemoprophylaxis, and the use of central venous catheters and other medical devices. Bacterial infections are common in the early stages of neutropenia, with fungal infections emerging if neutropenia persists beyond 7-10 days. Gram-positive organisms cause most bacteremic infections (although this trend appears to be changing), whereas infections at other sites are often caused by Gram-negative bacilli or are polymicrobial, especially if deep tissue infection is present. Candida spp., and Aspergillus spp., remain the most common fungal pathogens, although several opportunistic fungi have emerged. Resistance to antimicrobial and antifungal agents commonly used for the prevention and treatment of infections in neutropenic patients has become a significant problem. The prompt administration of appropriate, empiric, antimicrobial therapy, prior to the availability of microbiological culture results, is the standard of care. Up to date knowledge of the spectrum of infection and local susceptibility/resistance patterns, is critical. In this report, we describe the current spectrum of infection in patients with malignancies and neutropenia, and emphasize the fact that local and geographic differences are not infrequent. We recommend that individual institutions conduct periodic epidemiological surveys in order to have the latest data available for the optimal management of their patients.


Subject(s)
Antineoplastic Agents/therapeutic use , Bacteria/isolation & purification , Bacterial Infections/epidemiology , Chemotherapy-Induced Febrile Neutropenia/epidemiology , Fungi/isolation & purification , Mycoses/epidemiology , Neoplasms/drug therapy , Antineoplastic Agents/adverse effects , Bacteria/classification , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , Chemotherapy-Induced Febrile Neutropenia/microbiology , Fungi/classification , Humans , Mycoses/drug therapy , Mycoses/microbiology , Neoplasms/complications
11.
Support Care Cancer ; 22(1): 7-14, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23975231

ABSTRACT

PURPOSE: The goal of this study was to describe the outcomes associated with daptomycin treatment of documented gram-positive infections in patients with neutropenia. METHODS: All patients with neutropenia (≤500 cells/m(3)) and at least one documented gram-positive culture from 2006-2009 were identified from a retrospective, multicenter, and observational registry (Cubicin(®) Outcome Registry and Experience (CORE(®))). Investigators assessed patient outcome (cured, improved, failed, nonevaluable) at the end of daptomycin therapy. All patients were included in the safety analysis. RESULTS: The efficacy population had 186 patients; 159 (85 %) patients had either cure (n = 108, 58 %) or improved (n = 51, 27 %) as an outcome. Success rates (cure plus improved) by the lowest WBC during daptomycin were 98/116 (84 %) for ≤100 cells/m(3) and 61/70 (87 %) for 101-499 cells/m(3), P = 0.6. Most patients had cancer; 135/186 (73 %) had hematological malignancy; 26/186 (14 %) had solid tumors, and 9 (5 %) had both. One hundred fifty-six (84 %) patients received other antibiotics before daptomycin treatment; 82 % vancomycin, of which 31 % failed vancomycin. The most common infections were bacteremia (78 %), skin and skin structure infections (8 %), and urinary tract infections/pyelonephritis (6 %). The most common pathogens were vancomycin-resistant Enterococcus faecium (47 %), methicillin-resistant Staphylococcus aureus (20 %), and coagulase-negative staphylococci (19 %). The median (min, max) initial daptomycin dose was 6 mg/kg (3.6, 8.3). The median (min, max) daptomycin duration of therapy was 14 days (1, 86). Possibly related adverse events occurred in 12/209 patients (6 %), and 13 patients (6 %) discontinued daptomycin due to adverse event. CONCLUSIONS: The results suggest that daptomycin appeared useful and well tolerated in neutropenic patients, and the degree of neutropenia did not affect daptomycin success rates. Comparative clinical trials are needed to confirm these findings.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Daptomycin/therapeutic use , Gram-Positive Bacterial Infections/drug therapy , Neutropenia/microbiology , Adult , Aged , Anti-Bacterial Agents/adverse effects , Bacteremia/blood , Bacteremia/drug therapy , Daptomycin/adverse effects , Female , Gram-Positive Bacterial Infections/blood , Humans , Male , Middle Aged , Neoplasms/blood , Neoplasms/drug therapy , Neoplasms/microbiology , Neutropenia/chemically induced , Neutropenia/etiology , Retrospective Studies , Treatment Outcome , Vancomycin/therapeutic use
12.
Support Care Cancer ; 22(2): 527-35, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24141699

ABSTRACT

PURPOSE: Unlike infections related to chemotherapy-induced neutropenia, postoperative infections occurring in patients with solid malignancy remain largely understudied. Our aim is to evaluate the outcomes and the volume-outcomes relationship associated with postoperative infections following resection of common solid tumors. METHODS: We used Texas Discharge Data to study patients undergoing resection of cancer of the lung, esophagus, stomach, pancreas, colon, or rectum from 01/2002 to 11/2006. From their billing records, we identified ICD-9 codes indicating a diagnosis of serious postoperative infection (SPI), i.e., bacteremia/sepsis, pneumonia, and wound infection, occurring during surgical admission or leading to readmission within 30 days of surgery. Using regression-based techniques, we estimated the impact of SPI on mortality, resource utilization, and costs, as well as the relationship between hospital volume and SPI, after adjusting for confounders and data clustering. RESULTS: SPI occurred following 9.4 % of the 37,582 eligible tumor resections and was independently associated with nearly 12-fold increased odds of in-hospital mortality [95 % confidence interval (95 % CI), 7.2-19.5, P < 0.001]. Patients with SPI required six additional hospital days (95 % CI, 5.9-6.2) at an incremental cost of $16,991 (95 % CI, $16,495-$17,497). Patients who underwent resection at high-volume hospitals had a 16 % decreased odds of developing SPI than those at low-volume hospitals (P = 0.03). CONCLUSIONS: Due to the substantial burden associated with SPI following common solid tumor resections, hospitals must identify more effective prophylactic measures to avert these potentially preventable infections. Additional volume-outcomes research is needed to identify infection prevention processes that can be transferred from high- to lower-volume providers.


Subject(s)
Neoplasms/surgery , Postoperative Complications/microbiology , Sepsis/etiology , Surgical Procedures, Operative/statistics & numerical data , Surgical Wound Infection/etiology , Adult , Aged , Day Care, Medical , Female , Hospital Mortality , Humans , Male , Middle Aged , Neoplasms/economics , Neoplasms/epidemiology , Outcome Assessment, Health Care , Pneumonia/economics , Pneumonia/etiology , Pneumonia/mortality , Postoperative Complications/economics , Postoperative Complications/etiology , Postoperative Complications/mortality , Regression Analysis , Sepsis/economics , Sepsis/mortality , Surgical Procedures, Operative/adverse effects , Surgical Wound Infection/microbiology , Surgical Wound Infection/mortality , Texas/epidemiology
13.
Clin Infect Dis ; 56(5): 711-7, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23196957

ABSTRACT

Neutropenic enterocolitis (NEC) is a life-threatening disease with substantial morbidity and mortality, seen primarily in patients with hematologic malignancies. The frequency of NEC has increased with the widespread use of chemotherapeutic agents such as the taxanes, which cause severe gastrointestinal mucositis. Neutropenic patients with fever and abdominal symptoms (cramping, pain, distention, diarrhea, GI bleeding), should undergo evaluation of the abdomen for bowel wall thickening of >4 mm, the hallmark of NEC. Clostridium difficile infection should be ruled out, as well as other etiologies such as graft-versus-host disease. Complications include bacteremia, which is often polymicrobial, hemorrhage, and bowel wall perforation/abscess formation. Management includes bowel rest, correction of cytopathies and coagulopathies, and broad spectrum antibiotics and antifungal agents. Surgical intervention may be necessary to manage complications such as hemorrhage and perforation and should be delayed, if possible, until recovery from neutropenia.


Subject(s)
Antineoplastic Agents/adverse effects , Drug-Related Side Effects and Adverse Reactions , Enterocolitis, Neutropenic/chemically induced , Neoplasms/drug therapy , Taxoids/adverse effects , Algorithms , Enterocolitis, Neutropenic/physiopathology , Humans , Immunocompromised Host
14.
Oncologist ; 17(10): 1329-36, 2012.
Article in English | MEDLINE | ID: mdl-22707509

ABSTRACT

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) can cause significant morbidity and mortality in patients with cancer. However, data on outcomes of patients treated with vancomycin are lacking. METHODS: We identified 223 patients with cancer who developed MRSA BSIs between January 2001 and June 2009 and were treated with vancomycin. Treatment failure was defined as death within 60 days of infection, persistent bacteremia ≥5 days, fever ≥4 days, recurrence or relapse, and secondary MRSA infection. RESULTS: The treatment failure rate was 52% (116 of 223 patients). These patients were more likely to have been hospitalized, been treated with steroids within the previous 3 months, developed acute respiratory distress syndrome, required mechanical ventilation, required intensive care unit care, and community-onset infections (all p < .05). Risk factors for MRSA-associated mortality (27 of 223 patients; 12%) included hematologic malignancy and hematopoietic stem cell transplantation, community-onset infection, secondary BSI, MRSA with minimum inhibitory concentration (MIC) ≥2.0 µg/mL, mechanical ventilation, and a late switch to an alternative therapy (≥4 days after treatment failure; all p < .05). On multivariate analysis, mechanical ventilation and recent hospitalization were identified as independent predictors of vancomycin failure, and community-onset infection, secondary BSIs, and MIC ≥2 µg/mL were identified as significant predictors of MRSA-associated mortality. CONCLUSIONS: We found a high treatment failure rate for vancomycin in patients with cancer and MRSA BSIs, as well as a higher mortality. A vancomycin MIC ≥2 µg/mL was an independent predictor of MRSA-associated mortality. An early switch to an alternative therapy at the earliest sign of failure may improve outcome.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Neoplasms/microbiology , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Vancomycin/therapeutic use , Bacteremia/drug therapy , Bacteremia/microbiology , Female , Humans , Male , Middle Aged , Neoplasms/blood , Retrospective Studies , Treatment Outcome
15.
J Clin Microbiol ; 50(5): 1552-7, 2012 May.
Article in English | MEDLINE | ID: mdl-22378911

ABSTRACT

Effective skin antisepsis is of central importance in the prevention of wound infections, colonization of medical devices, and nosocomial transmission of microorganisms. Current antiseptics have a suboptimal efficacy resulting in substantial infectious morbidity, mortality, and increased health care costs. Here, we introduce an in vitro method for antiseptic testing and a novel alcohol-based antiseptic containing 4 to 5% of the polar aprotic solvent dimethyl sulfoxide (DMSO). The DMSO-containing antiseptic resulted in a 1- to 2-log enhanced killing of Staphylococcus epidermidis and other microbes in vitro compared to the same antiseptic without DMSO. In a prospective clinical validation, blood culture contamination rates were reduced from 3.04% for 70% isopropanol-1% iodine (control antiseptic) to 1.04% for 70% isopropanol-1% iodine-5% DMSO (P < 0.01). Our results predict that improved skin antisepsis is possible using new formulations of antiseptics containing strongly polarized but nonionizing (polar aprotic) solvents.


Subject(s)
Anti-Infective Agents, Local/pharmacology , Blood/microbiology , Dimethyl Sulfoxide/pharmacology , Skin/microbiology , 2-Propanol/pharmacology , Adult , Bacterial Load , Drug Synergism , Female , Humans , Iodine/pharmacology , Male , Microbial Viability/drug effects , Middle Aged , Staphylococcus epidermidis/drug effects
17.
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.

18.
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
19.
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.

20.
Clin Infect Dis ; 63(5): 707-8, 2016 09 01.
Article in English | MEDLINE | ID: mdl-27318331

Subject(s)
Neoplasms , Pneumonia , Humans
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