Clinical characteristics and risk factors associated with Pneumocystis jirovecii infection in patients with solid tumors: study of thirteen-year medical records of a large cancer center.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP)-related risk factors among patients with solid tumors are not completely defined. Thus, we aimed to characterize PCP cases with underlying solid tumors, to highlight the factors contributing to its development besides the prolonged use of moderate-to-high dose corticosteroids. METHODS: We retrospectively reviewed the medical records of patients with solid tumors diagnosed with PCP between 2006 and 2018 at a cancer center in Tokyo, Japan. Demographic and clinical data were collected, which included malignancy types, total lymphocyte count, coexisting pulmonary disease, chemotherapy, radiation therapy, corticosteroid use, and PCP-attributable mortality. RESULTS: Twenty cases of PCP with solid tumors were documented in 151,718 patients and 788,914 patient-years. Lung cancer (n = 6, 30%) was the most common underlying tumor, followed by breast cancer (n = 3, 15%). Only six (30%) patients were taking a dosage of ≥20 mg prednisone equivalents daily for ≥4 weeks from the onset of PCP. Among the remaining 14 patients, seven (50%) had coexisting pulmonary diseases, 10 (71%) had received chemotherapy within 90 days prior to PCP diagnosis, seven (50%) had undergone chest radiation therapy before PCP diagnosis, seven (50%) had received only intermittent corticosteroids, and one (7%) received no corticosteroids. Mortality attributable to PCP was 40%. CONCLUSIONS: More than half of the patients were not taking a dosage of ≥20 mg prednisone equivalents daily for ≥4 weeks. Multiple other factors (e.g., lymphocytopenia, radiation to chest) may have potentially contributed to PCP in patients with solid tumors in a composite manner. We need to establish a method for estimating the likelihood of PCP taking multiple factors into account in this patient population.

Institutional outbreak involving multiple clades of IMP-producing Enterobacter cloacae complex sequence type 78 at a cancer center in Tokyo, Japan.

BACKGROUND: Information about the clinical and microbiological characteristics of IMP-producing Enterobacterales has been limited. Here, we describe an institutional outbreak of IMP-producing Enterobacter cloacae complex (ECC) involving multiple clades of ECC sequence type (ST) 78 strains. METHODS: Antimicrobial susceptibility testing, whole-genome sequencing, and conjugation experiments of 18 IMP-producing ECC strains isolated during four-year study period were performed. Species and subspecies were determined by average nucleotide identity analysis and clonal relatedness of the isolates was analyzed with multilocus sequence typing and core-genome single nucleotide polymorphism (SNP) analysis. Relevant clinical information was extracted from medical records. RESULTS: Fourteen of 18 IMP-producing ECC isolates were determined as Enterobacter hormaechei ST78. Sixteen isolates, including 13 isolates belonging to ST78, carried blaIMP-1 in In316-like class 1 integron and also carried IncHI2 plasmids. Conjugation experiments were successful for 12 isolates carrying blaIMP-1 on IncHI2 plasmids and for an isolate carrying blaIMP-11 on an IncL/M plasmid. Although isolation of ST78 strains was clustered in a 14-months period suggesting nosocomial transmission, these strains were subdivided into three clades by SNP analysis: clade A (n = 10), clade B (n = 1), clade C (n = 3). A part of clonal relatedness was unexpected by the epidemiological information at the time of isolation of the strains. Most of the IMP-producing ECC strains were susceptible to non-ß-lactam antibiotics and had relatively low minimum inhibitory concentrations to carbapenems (≤4 µg/mL). Five of six infections caused by IMP-producing ECC were treated successfully. CONCLUSIONS: Whole-genome sequencing analysis revealed the outbreak was caused by three different clades of ST78 strains, where patients had favorable treatment outcome of the infections compared with that caused by Enterobacterales producing other carbapenemases, possibly due to their non-multidrug-resistant phenotype.

Infected aortic aneurysm caused by Helicobacter cinaedi: case series and systematic review of the literature.

BACKGROUND: Helicobacter cinaedi is rarely identified as a cause of infected aneurysms; however, the number of reported cases has been increasing over several decades, especially in Japan. We report three cases of aortic aneurysm infected by H. cinaedi that were successfully treated using meropenem plus surgical stent graft replacement or intravascular stenting. Furthermore, we performed a systematic review of the literature regarding aortic aneurysm infected by H. cinaedi. CASE PRESENTATION: We present three rare cases of infected aneurysm caused by H. cinaedi in adults. Blood and tissue cultures and 16S rRNA gene sequencing were used for diagnosis. Two patients underwent urgent surgical stent graft replacement, and the other patient underwent intravascular stenting. All three cases were treated successfully with intravenous meropenem for 4 to 6 weeks. CONCLUSIONS: These cases suggest that although aneurysms infected by H. cinaedi are rare, clinicians should be aware of H. cinaedi as a potential causative pathogen, even in immunocompetent patients. Prolonged incubation periods for blood cultures are necessary for the accurate detection of H. cinaedi.

Fatal invasive pulmonary aspergillosis caused by voriconazole-resistant Aspergillus tubingensis in a patient with solid tumor.

We report a fatal case of invasive pulmonary aspergillosis caused by voriconazole-resistant Aspergillus tubingensis in a patient with solid tumor but without severe immunosuppression. A high index of suspicion for invasive pulmonary aspergillosis, coupled with molecular identification of species and resistance genes, may facilitate early initiation of appropriate treatment.

Outbreak of Streptococcus pyogenes emm89 ST646 in a head and neck surgical oncology ward.

Streptococcus pyogenes causes a variety of human infections, and hospital outbreaks with this pathogen have also been reported. The purpose of this study is to describe the clinical characteristics of an outbreak of S. pyogenes involving 15 patients and four healthcare workers (HCWs), as well as the molecular characteristics of the causative isolates. The course and response to the outbreak were reviewed, and information on the characteristics of the patients was extracted retrospectively from the medical records. Whole-genome sequencing of the 16 causative isolates (14 from patients and two from HCWs) was also performed. All 15 patients were postoperative of head and neck cancer with tracheotomy, and 12 had invasive infections, primarily surgical site infections, all of which resolved without causing serious illness. All but the first case was detected more than 7 days after admission. S. pyogenes was detected in two patients after empiric antimicrobial administration was performed on all inpatients and HCWs, and the outbreak was finally contained in approximately 2 months. All isolates detected in patients and HCWs belonged to emm89/clade 3, a hypervirulent clone that has emerged worldwide and was classified as sequence type 646. These isolates had single nucleotide polymorphism (SNP) differences of zero to one, indicating clonal transmission. This study demonstrated an outbreak of S. pyogenes emm89/clade 3 in a ward of patients with head and neck cancer. The global emergence of hypervirulent isolates may increase the risk of outbreaks among high-risk patients. IMPORTANCE: This study describes an outbreak of Streptococcus pyogenes that occurred in a ward caring for patients with head and neck cancer and tracheostomies. Many cases of invasive infections occurred in a short period, and extensive empiric antimicrobial administration on patients and healthcare workers was performed to control the outbreak. Whole-genome sequencing analysis of the causative strains confirmed that it was a monoclonal transmission of strains belonging to emm89/clade 3. The epidemiology and clinical characteristics of S. pyogenes infections have changed with the replacement of the prevalent clones worldwide. In the 1980s, there was a reemergence of S. pyogenes infections in high-income countries due to the spread of hypervirulent emm1 strains. emm89/clade 3 has recently been spreading worldwide and shares common features with emm1, including increased production of two toxins, NADase, and streptolysin O. The outbreak reported here may reflect the high spreading potential and virulence of emm89/clade 3.

An effective active surveillance method for controlling nosocomial MRSA transmission in a Japanese hospital.

Hospital-wide active surveillance for methicillin-resistant Staphylococcus aureus (MRSA) targeted to adult patients with a history of MRSA carriage within the past 5 years was performed in Juntendo University Hospital (JUH) over a 2-year period. In the first year, MRSA screening culture was ordered by physicians in charge. In the second year, infection-control practitioners (ICPs) took samples for active surveillance culture. The average monthly transmission rate of MRSA in JUH was 0.35 per 1,000 bed-days in the first year and decreased significantly to 0.26 per 1,000 bed-days in the second year (P < 0.05). In the second year, more active commitment of ICPs to MRSA screening was effective in improving the performance rate of screening, shortening turn-around time of screening results, and decreasing transmission rate. Increasing compliance with active MRSA surveillance by involvement of ICPs, targeting patients with a previous history of MRSA carriage in the previous 5 years, was effective to control nosocomial MRSA transmission.

Clinical Features, Genome Epidemiology, and Antimicrobial Resistance Profiles of Aeromonas spp. Causing Human Infections: A Multicenter Prospective Cohort Study.

Background: The genus Aeromonas is increasingly implicated in human infections, but knowledge of its clinical characteristics and antimicrobial resistance profiles has been limited owing to its complex taxonomy. Methods: We conducted a multicenter prospective cohort study of patients with Aeromonas infections at hospitals across Japan. Patients were eligible for inclusion if they had an Aeromonas spp. strain in a clinical culture and were considered infected at the culture site. Clinical data were collected, and isolates underwent susceptibility testing and whole-genome sequencing. Results: A total of 144 patients were included. Hepatobiliary infection accounted for a majority of infections (73% [105 of 144]), which mostly occurred in elderly patients with comorbid conditions, including hepatobiliary complications. The all-cause 30-day mortality rate was 10.0% (95% confidence interval, 4.9%-14.8%). By whole-genome sequencing, 141 strains (98%) belonged to 4 Aeromonas species-A caviae, A hydrophila, A veronii, and A dhakensis-with significant intraspecies diversity. A caviae was predominant in all infection sites except skin and soft tissue, for which A hydrophila was the prevailing species. The genes encoding chromosomally mediated class B, C, and D ß-lactamases were harbored by 92%-100% of the isolates in a species-specific manner, but they often lacked association with resistance phenotypes. The activity of cefepime was reliable. All isolates of A hydrophila and A dhakensis carried an mcr-3-like colistin resistance gene and showed reduced susceptibility to colistin. Conclusions: Hepatobiliary tract was the most common infection site of Aeromonas spp., with A caviae being the dominant causative species. The resistance genotype and phenotype were often incongruent for ß-lactam agents.

Comparison of the Treatment Outcome of Piperacillin-Tazobactam versus Carbapenems for Patients with Bacteremia Caused by Extended-Spectrum ß-Lactamase-Producing Escherichia coli in Areas with Low Frequency of Coproduction of OXA-1: a Preliminary Analysis.

Although piperacillin-tazobactam (TZP) was shown to be less effective than carbapenems in treating bacteremia due to extended-spectrum ß-lactamase-producing (ESBL)-producing organisms in a randomized controlled trial, the fact that many of the causative organisms co-produced inhibitor-resistant OXA-1 along with ESBLs may have influenced the results. In this study, we compared the therapeutic effectiveness of TZP and carbapenem in treating ESBL-producing Escherichia coli bacteremia in areas with low frequency of OXA-1 co-production. Forty patients, 14 in the TZP treatment group and 26 in the carbapenem treatment group, were included in the analysis. There were no significant differences in patient background between the two groups. Urinary tract infection or cholangitis was the source of bacteremia in 26 patients (65%), and the Pitt bacteremia score was zero or one in 35 patients (87.5%). Only four (11.4%) of the 35 causative isolates available for microbiological analysis harbored blaOXA-1, and only three (8.6%) were non-susceptible to TZP. Seventeen (48.6%) isolates carried blaCTX-M-27, none of which carried other ß-lactamase genes. No significant difference in the frequency of treatment failure on day 14 of bacteremia was documented between the TZP and carbapenem treatment groups in both the crude analysis and the inverse probability of treatment weighting-adjusted analysis. This study demonstrates that TZP may be a treatment option for non-severe cases of ESBL-producing E. coli bacteremia in areas with low frequency of OXA-1 co-production. IMPORTANCE Although carbapenems are considered the drug of choice for severe infections caused by extended-spectrum ß-lactamase-producing (ESBL)-producing organisms, other therapeutic options are being explored to avoid increasing the selective pressure for carbapenem-resistant organisms. In this study, it was suggested that piperacillin-tazobactam may be as effective as carbapenems for the treatment of mild bacteremia caused by ESBL-producing Escherichia coli in areas where OXA-1 co-production by ESBL-producing E. coli is rare. The genetic background of each regional epidemic clone differs even among multidrug-resistant bacteria classified under the same name (e.g., ESBL-producing organisms), resulting in possible differences in the efficacy of therapeutic agents. Exploration of treatment options for multidrug-resistant organisms according to local epidemiology is worthwhile from the perspective of antimicrobial stewardship.

Clinical characteristics of peripheral venous catheter-associated gram-negative bloodstream infection among patients with malignancy.

PURPOSE: Previous studies have suggested that peripheral venous catheter is a significant source of gram-negative bacteraemia in patients with malignancy. We aimed to identify risk factors and develop a clinical prediction rule for the involvement of gram-negative organisms in peripheral venous catheter-associated bloodstream infections (PVC-BSIs) among patients with malignancy. METHODS: This retrospective cohort study was conducted at a 700-bed cancer hospital in Japan. Consecutive patients diagnosed with PVC-BSI based on clinical and microbiological criteria were included in this study. Based on clinical and microbiological characteristics of PVC-BSIs in cancer patients, a logistic regression model for predicting gram-negative organisms as causative organisms in PVC-BSIs was then developed. RESULTS: Of the 99 patients included in our cohort, 60 patients (60.6%) had gram-negative PVC-BSIs. The median age of patients with PVC-BSIs was 67 years (interquartile range [IQR], 59-74 years), and the median Pitt bactearemia score was 1 (IQR, 0-3). The median duration of catherization was 5 days (IQR, 4-7 days) and 70 patients (70.7%) received peripheral parenteral nutrition that contained amino acids. On multivariable analysis, age ≥65 years (odds ratio [OR], 3.07; 95% confidence interval [CI], 1.10-8.62), showering (OR, 3.15; 95% CI, 1.07-9.26), Pitt bacteraemia score ≥2 points (OR, 6.96; 95% CI, 2.52-19.2), and use of peripheral parenteral nutrition (OR, 0.31; 95% CI, 0.10-0.98) were independent predictors for gram-negative PVC-BSIs among all PVC-BSIs. The simplified PVC-GN scores established to predict gram-negative PVC-BSIs had a optimism-corrected c-index of 0.775. CONCLUSION: Gram-negative bacteria were more commonly responsible for PVC-BSI than Gram-positive bacteria among cancer patients in this cohort. Involvement of Gram-negative bacteria in PVC-BSIs could be predicted with readily available clinical variables.