The in vitro activity of delafloxacin and comparator agents against bacterial pathogens isolated from patients with cancer.

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.

In vitro activity of eravacycline and comparator agents against bacterial pathogens isolated from patients with cancer.

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.

Bloodstream Infections in Hematologic Malignancy Patients With Fever and Neutropenia: Are Empirical Antibiotic Therapies in the United States Still Effective?

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.

In vitro activity of imipenem/releactam and comparator agents against clinical bacterial isolates from patients with cancer.

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.

Activity of Cefiderocol and Comparators against Isolates from Cancer Patients.

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.

Evaluation of Current Perioperative Antimicrobial Regimens for the Prevention of Surgical Site Infections in Breast Implant-based Reconstructive Surgeries.

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.

Risk factors for recurrent percutaneous nephrostomy catheter-related infections.

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.

Infections with the agent of 'kennel cough' in patients with cancer.

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.

Antimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline Update.

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 .

In vitro activity of tedizolid and comparator agents against clinical Gram-positive isolates recovered from patients with cancer.

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.

Post-Obstructive Pneumonia in Patients with Cancer: A Review.

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.

Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice Guideline Update.

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 .

In vitro activity of ceftaroline and comparator agents against Gram-positive and Gram-negative clinical isolates from cancer patients.

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.

Infections in Cancer Patients with Solid Tumors: A Review.

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.

Time-kill determination of the bactericidal activity of telavancin and vancomycin against clinical methicillin-resistant Staphylococcus aureus isolates from cancer patients.

The bactericidal activity of vancomycin and telavancin was compared against 4 clinical methicillin-resistant Staphylococcus aureus isolates recently recovered from cancer patients, using minimum bactericidal concentration (MBC):MIC ratios and time-kill studies. All 4 isolates were susceptible to both agents based on individual MIC values. The 2 methodologies for assessing bactericidal activity produced variable results. Telavancin appeared to have somewhat better bactericidal activity than vancomycin based on narrower MBC:MIC ratios. However, based on the results of the time-kill studies, neither agent demonstrated reliable bactericidal activity (defined as a ≥3 log10 reduction of the starting inoculum at the end of 24hours) against these organisms. These findings might be of some therapeutic importance in certain clinical settings and/or specific patient populations (such as febrile neutropenic patients) in whom potent bactericidal activity is either desired or preferred.

Antimicrobial Activities of Ceftazidime-Avibactam and Comparator Agents against Clinical Bacteria Isolated from Patients with Cancer.

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.

Staphylococcus lugdunensis infections, filling in the gaps: a 3-year retrospective review from a comprehensive cancer center.

OBJECTIVE: Staphylococcus lugdunensis is considered to be more aggressive than other coagulase-negative staphylococci (CoNS). There are gaps in knowledge regarding the importance of isolating S. lugdunensis from different sources and in different patient subsets. Our objective was to describe the spectrum, clinical manifestations, and outcomes of infections caused by S. lugdunensis in patients with cancer. METHODS: A retrospective review of all cancer patients from whom S. lugdunensis was isolated in a pure culture from clinically significant sites. RESULTS: Between 2011 and 2014, 2263 CoNS were isolated, of them 45 S. lugdunensis were isolated in a pure culture and were included in this analysis. Only three patients were neutropenic. Skin and skin structure infections (SSSIs) occurred most often (36 cases) followed by five blood stream infections, one of which had destructive endocarditis and four infections at other sites. Of the 36 SSSIs, 29 were related to surgical or invasive procedures, and six of these involved an implanted medical device. All isolates were susceptible to vancomycin, 98% to levofloxacin and 89% to oxacillin. All patients responded to the therapy. CONCLUSIONS: Cancer patients including those with neutropenia do not appear to have an increased frequency of infections caused by S. lugdunensis. SSSIs are predominant and are often associated with surgical procedures and/or implanted medical devices. Blood stream infections caused by S. lugdunensis are uncommon but may have an increased rate of serious complications such as endocarditis. Nevertheless, these organisms are generally susceptible to multiple classes of antimicrobial agents, and the overall response to therapy is high.