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Abstract Background The prognosis of immunocompromised individuals with COVID-19 remains a significant concern. Information regarding the clinical and virological characteristics of immunocompromised patients infected with SARS-CoV-2 during the Omicron variant period is limited. Methods Medical records of patients admitted to our hospital with COVID-19 during the Omicron (BA.1–5) epidemic were retrospectively reviewed. Clinical, virological (nasopharyngeal swabs and blood), and serological data were compared between immunocompromised patients receiving immunosuppressive medications (calcineurin inhibitors, mycophenolate mofetil, or steroids) and control patients not receiving immunosuppressive medications. Results Twenty-eight immunocompromised patients (25 transplant recipients) and 26 control patients were included. Fourteen of the immunocompromised patients (50%) received monoclonal antibodies. The immunocompromised group included 15 mild/moderate (53.6%), 10 severe (35.7%), and three critical (10.7%) disease severities. The mortality rate due to COVID-19 during hospitalization was 3.6% (1/28) in the immunocompromised group, with no difference between the two groups. Three cases of re-exacerbation after discharge occurred in the immunocompromised group and none in the control group. Linear regression based on nasopharyngeal real-time-PCR cycle threshold (Ct) values according to the time since symptom onset showed markedly slower viral clearance in the immunocompromised group than in the control group (P slope = 0.078). In the immunocompromised group, patients who received monoclonal antibodies showed faster viral clearance than those who did not receive monoclonal antibodies. The convalescent anti-spike IgG titers were comparable to those in the control group in patients who received monoclonal antibodies and significantly lower than those in the control patients in patients who did not receive monoclonal antibodies (P

ABSTRACT Evaluating SARS-CoV-2 viral loads in nasopharyngeal (NP) and saliva samples, factors affecting viral loads, and the performance of rapid antigen testing (RAT) have not been comprehensively conducted during SARS-CoV-2 Omicron epidemic. This prospective study included outpatients enrolled during Omicron variant period in Japan. Paired NP swab and saliva samples were collected to measure viral loads by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The correlation between viral loads and clinical symptoms was examined. The performance of an immunochromatography-based RAT kit was also assessed. A total of 153 patients tested within 3 days of symptom onset were included. The mean viral load was 5.60 log10 copies/test and 3.65 log10 copies/test in NP and saliva samples, respectively, resulting in a significant difference (P < 0.0001). Fever over 37°C (axillary temperature) and total number of symptoms other than fever were identified as independent factors positively correlated with the viral loads in both NP and saliva samples. RAT sensitivity using NP and saliva samples was 92% and 68%, respectively, using positive RT-qPCR results as the reference. The sensitivity of RAT using NP and saliva samples was significantly higher in patients with fever ≥37°C and/or at least one symptom than in those with fever

Background: SARS-CoV-2 mRNA vaccination, recognized for high immunogenicity, frequently induces adverse reactions, especially fever. We previously reported a correlation between post-vaccination fever and specific antibody responses to the primary series and first booster. We herein report changes in adverse reactions and the correlation between post-vaccination fever and antibody responses across successive vaccinations, from monovalent to bivalent mRNA vaccines. Methods: This cohort study was conducted at a Japanese hospital to investigate adverse reactions to the monovalent primary, first booster, and BA.4/5 bivalent BNT162b2 vaccinations. Local and systemic reactions were reported through a self-reporting diary after each dose. The spike-specific IgG titers were measured following each vaccination. Results: Across 727 vaccinations in the vaccine series, the bivalent booster induced fewer adverse reactions than earlier doses. Fever ≥ 38.0 °C was significantly less frequent in the bivalent booster (12.3 %) compared to the primary series and monovalent booster (22.0 %, 26.2 %, p

Objectives: Differences in virulence genes, including psm-mec, which is a phenol-soluble modulin-mec (PSM-mec) encoding gene, of predominant staphylococcal cassette chromosome mec (SCCmec) types II and IV Methicillin-resistant Staphylococcus aureus (MRSA) may contribute to the virulence and clinical features of MRSA in Japan. We aimed to clarify the clinical characteristics and risk factors of infection among SCCmec types II and IV MRSA isolates from a Japanese secondary acute care hospital. Methods: We analysed 58 SCCmec type II and 83 SCCmec type IV MRSA isolates collected from blood, central venous catheter tips, deep or superficial tissues, and sputum. Results: SCCmec type II MRSA risk factors for progression to infection were seb, enterotoxin gene cluster, psm-mec mutation, and vancomycin minimum inhibitory concentrations (MIC) of 1 or 2 mg/L as virulence factors (adjusted odds ratio [aOR] = 11.8; 95% confidence interval [CI]: 2.49–77.7; P = 0.004); solid tumour was a host factor (aOR = 25.9; 95% CI: 3.66–300; P = 0.003). SCCmec type IV MRSA risk factors were sea, cna, and vancomycin MIC of 1 or 2 mg/L as virulence factors (aOR = 3.14; 95% CI: 1.06–10.6; P = 0.049) and intravascular indwelling catheter as host factors (aOR = 3.78; 95% CI: 1.03–14.5; P = 0.045). Compared with SCCmec type II, SCCmec type IV MRSA resulted in more frequent bloodstream infections and higher Sequential Organ Failure Assessment scores. Conclusion: We found that factors related to virulence genes and bacteriological and host characteristics are associated with SCCmec types II and IV MRSA infection and severity. These risk factors may be useful criteria for designing infection control programs.

Abstract Background Infection control during COVID‐19 outbreaks in nursing facilities is a critical public health issue. Antibody responses before and after the fourth (second booster) dose of wild‐type severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccine in nursing home residents have not been fully characterized. Methods This study included 112 individuals: 54 nursing home residents (mean age: 84.4 years; 35 SARS‐CoV‐2‐naive and 19 previously infected) and 58 healthcare workers (mean age: 47.7 years; 25 SARS‐CoV‐2‐naive and 33 previously infected). Antispike and antinucleocapsid antibody responses to messenger RNA vaccination were evaluated using serum samples collected shortly and 5 months after the third dose, and shortly after the fourth dose. Results The median immunoglobulin G (IgG) level in SARS‐CoV‐2‐naive residents was similar to that in SARS‐CoV‐2‐naive healthcare workers after the fourth dose (24,026.3 vs. 30,328.6 AU/mL, p = .79), whereas after the third dose the IgG level of SARS‐CoV‐2‐naive residents was approximately twofold lower than that in SARS‐CoV‐2‐naive healthcare workers. In residents with previous SARS‐CoV‐2 infection, timing of infection in relation to vaccination affected the kinetics of antibody responses. Residents infected after the third dose showed the highest IgG levels after the fourth dose among all groups (median: 64,328.8 AU/mL), in contrast to residents infected before initiating vaccination with antibody levels similar to those of SARS‐CoV‐2‐naive residents. Conclusions Advanced aged nursing home residents, poor responders in the initial SARS‐CoV‐2 vaccine series, could achieve sufficient antibody responses after the fourth (second booster) vaccination, comparable to those of younger adults.

ABSTRACT Neutralizing potency of humoral immune responses induced by prior infection or vaccination is vital for protecting of individuals and population against severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). However, the emergence of viral variants that can evade neutralization by vaccine- or infection-induced immunity is a significant public health threat and requires continuous monitoring. Here, we have developed a novel scalable chemiluminescence-based assay for assessing SARS-CoV-2-induced cytopathic effect to quantify the neutralizing activity of antisera. The assay leverages the correlation between host cell viability and ATP levels in culture to measure the cytopathic effect on target cells induced by clinically isolated, replication-competent, authentic SARS-CoV-2. With this assay, we demonstrate that the recently arisen Omicron subvariants BQ.1.1 and XBB.1 display a significant decrease in sensitivity to neutralization by antibodies elicited from breakthrough infections with Omicron BA.5 and from receipt of three doses of mRNA vaccines. Thus, this scalable neutralizing assay provides a useful platform to assess the potency of acquired humoral immunity against newly emerging SARS-CoV-2 variants. IMPORTANCE The ongoing global pandemic of SARS-CoV-2 has emphasized the importance of neutralizing immunity in protecting individuals and populations against severe respiratory illness. In light of the emergence of viral variants with the potential to evade immunity, continuous monitoring is imperative. A virus plaque reduction neutralization test (PRNT) is a “gold standard” assay for analyzing neutralizing activity for authentic viruses that form plaques, like influenza virus, dengue virus, and SARS-CoV-2. However, this method is labor intensive and is not efficient for performing large-scale neutralization assays on patient specimens. The assay system established in this study allows for the detection of a patient's neutralizing activity by simply adding an ATP detection reagent, providing a simple evaluation system for neutralizing activity of antisera as an alternative to the plaque reduction method. Our extended analysis of the Omicron subvariants highlights their increasing capability to evade neutralization by both vaccine- and infection-induced humoral immunity.

Summary: The efficacy of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the elderly is partially hindered by immunosenescence, resulting from decreased mtDNA levels. This study evaluated the correlation between mtDNA levels in peripheral leukocytes and immune response to the SARS-CoV-2 vaccine. Two hundred ten participants (median age 79.5 years), including 83 frail residents/inpatients and 70 robust outpatients, were analyzed. Anti-spike IgG antibody (IgG(S)) titers were serially measured from before the first vaccination to after the third vaccination. The mtDNA levels and cell-mediated immunity were measured in 45 elderly and 22 elderly individuals two months after the third vaccination. The robust group had consistently higher IgG(S) titers than the frail group. The mtDNA levels positively correlated with IgG(S) titers, as well as with cell-mediated immunity. These findings suggest that mtDNA levels positively impact vaccine-induced immunity. Further studies into maintaining mtDNA levels may provide insights into immunosenescence in the elderly.

ABSTRACT: Objectives: The dissemination of difficult-to-treat carbapenem-resistant Enterobacterales (CRE) is of great concern. We clarified the risk factors underlying CRE infection mortality in Japan. Methods: We conducted a retrospective, multicentre, observational cohort study of patients with CRE infections at 28 university hospitals from September 2014 to December 2016, using the Japanese National Surveillance criteria. Clinical information, including patient background, type of infection, antibiotic treatment, and treatment outcome, was collected. The carbapenemase genotype was determined using PCR sequencing. Multivariate analysis was performed to identify the risk factors for 28-day mortality. Results: Among the 179 patients enrolled, 65 patients (36.3%) had bloodstream infections, with 37 (20.7%) infections occurring due to carbapenemase-producing Enterobacterales (CPE); all carbapenemases were of IMP-type (IMP-1: 32, IMP-6: 5). Two-thirds of CPE were identified as Enterobacter cloacae complex. Combination therapy was administered only in 46 patients (25.7%), and the 28-day mortality rate was 14.3%. Univariate analysis showed that solid metastatic cancer, Charlson Comorbidity Index ≥3, bloodstream infection, pneumonia, or empyema, central venous catheters, mechanical ventilation, and prior use of quinolones were significant risk factors for mortality. Multivariate analysis revealed that mechanical ventilation (OR: 6.71 [1.42–31.6], P = 0.016), solid metastatic cancers (OR: 5.63 [1.38–23.0], P = 0.016), and bloodstream infections (OR: 3.49 [1.02–12.0], P = 0.046) were independent risk factors for 28-day mortality. Conclusion: The significant risk factors for 28-day mortality in patients with CRE infections in Japan are mechanical ventilation, solid metastatic cancers, and bloodstream infections.

Abstract Background Awareness of pre-travel consultations (PTCs) and prevention methods for overseas travel-related diseases, and the understanding of PTCs among Japanese travelers and medical professionals remains low in Japan. A multicenter registry was established to examine PTCs in Japan. This study assessed the PTC implementation rate and examined the indicators of PTCs that can be used as criteria for evaluating quality. Methods Clients who presented for their PTCs at 17 facilities and were registered between February 1, 2018, and May 31, 2020, were included. Medical information was extracted retrospectively via a web-based system. Correlations between vaccination risk categories and advice/intervention proportions by the facility were evaluated using Spearman’s ordered phase relations (α = 0.05). Results Of the 9700 eligible clients (median age, 32 years; 880 [9.1%] aged

Objectives: Many countries are administering a third dose of some coronavirus disease 2019 (COVID-19) vaccines, but the evaluation of vaccine-induced immunity after boosting in East Asia is insufficient. This study aimed to evaluate anti-spike immunoglobulin G [IgG(S)] titers after the third BNT162b2 vaccination. Methods: The dynamics of IgG(S) titers were assessed two months following the third BNT162b2 vaccination in 52 participants. All participants received the primary series of vaccination with BNT162b2 and received the third dose eight months after the second vaccination. Associations among the IgG(S) titer, baseline characteristics, and adverse reactions were also evaluated. Results: The geometric mean titer of IgG(S) one month after the third vaccination was 17,400 AU/ml, which increased by approximately 30 times that immediately before the third vaccination. The rate of IgG(S) titer decline was significantly slower after the third vaccination (35.7%) than after the second vaccination (59.1%). The IgG(S) titer was significantly negatively associated with age (r = −0.31). Participants who had a headache at the time of vaccination showed significantly higher IgG(S) titers than those without a headache. Conclusions: The IgG(S) titer induced by primary immunization with BNT162b2 waned over time. The third dose of BNT162b2 substantially increased the IgG(S) titer, with a slower rate of decline.

The relation between pre-vaccination antipyretic use and antibody responses to SARS-CoV-2 vaccination has been unclear. We measured the pre- and post-BNT162b2 booster spike-specific IgG titers and recorded antipyretic use and adverse reactions for SARS-CoV-2-naive hospital healthcare workers. The data of 20 cases who used antipyretics within 24 h before vaccination were compared to that of 281 controls. The post-booster geometric mean IgG titers were 15,559 AU/mL (95 % CI, 11,474–21,203) for the cases and 16,850 AU/mL (95 % CI, 15,563–18,243) for the controls (p = 0.622). No significant reduction in the frequency or severity of any of the solicited adverse reactions was found for the cases. Similar results were obtained after adjustment with propensity-score matching for demographic characteristics, baseline IgG titer, and post-vaccination antipyretic use. Antipyretic use within 24 h before vaccination would not affect mRNA COVID-19 vaccine-induced specific antibody responses and that postponement of vaccination due to pre-vaccination antipyretic use would be unnecessary.

Abstract Background The Pandemic of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has critically impacted the spread of infection within nursing facilities. We evaluated the usefulness of genetic and serological tests conducted during a COVID-19 outbreak in a nursing facility in Japan. Methods After the first identification of SARS-CoV-2 infection, a comprehensive, facility- and/or unit-wide PCR testing from nasopharyngeal swabs was repeatedly performed in a three-unit facility including 99 residents with dementia and 53 healthcare personnel. Additionally, PCR testing was conducted separately for residents and staff with fever of ≥37.5 °C. Facility-wide serological testing, including rapid kit testing and quantitative assay, was conducted twice over 1 month apart. Results A total of 322 PCR and 257 antibody tests were performed. 37 (24.3%) of the 152 individuals (25/99 residents, 25.3%; 12/53 staff, 22.6%) were identified as PCR-positive. Seven residents died with a mortality of 7.1% (7/99). Among the 37 individuals, 10 (27.0%) were asymptomatic at the time of testing. PCR positivity was concentrated on one unit (Unit 1) (20/30 residents, 66.7%; 9/14 staff, 64.3%). The other units showed a limited spread of infection. In unit-wide and separate tests, PCR positivity detection was highly prevalent (22.9 and 44.4%, respectively) in Unit 1, compared with that in the other units. Serological testing identified two additional infected residents with a negative PCR result and showed that no staff was newly identified as infected. Conclusions Thorough PCR testing, in combination with comprehensive and separate tests, is critical for managing COVID-19 outbreaks in nursing facilities, particularly, in units considered an epicenter. Serological testing is also beneficial for tracing contacts, confirming the number of infected individuals, and authorizing the termination of the outbreak.

Objectives: Antimicrobial stewardship is a strategy to combat antimicrobial resistance in hospitals. Given the burden and impact of antimicrobial resistance in the Asia Pacific, it is important to document capacity and gaps in antimicrobial stewardship programmes (ASP). We aimed to understand existing capacities and practices, and define the resources needed to establish antimicrobial stewardship where it is lacking. Methods: An anonymous online survey, consisting of questions on antimicrobial control at country, hospital and programme levels, was circulated to healthcare providers in the field of infectious diseases and microbiology through Asian Network for Surveillance of Resistant Pathogens, ReAct Group and the Australasian Society for infectious Diseases. Results: 139 participants from 16 countries or regions completed the survey. The majority of participants were adult infectious diseases physicians (61/139, 43.9%) and microbiologists (31/139, 22.3%). Participants from 7 countries reported that antimicrobials can be obtained without prescriptions. Despite the high percentage (75.5%) of respondents working in large hospitals, only 22/139 participants (15.8%) from Australia, China, Singapore, Taiwan, Thailand and Vietnam reported having more than 10 infectious diseases physicians. Hospital empiric antimicrobial guidelines for common infections were available according to 110/139 (79.1%) participants. Pre-authorisation of antimicrobials was reported by 88/113 (77.9%) respondents while prospective audit and feedback was reported by 93/114 (81.6%). Automatic stop orders and culture-guided de-escalation were reported by only 52/113 (46.0%) and 27/112 (24.1%) respectively. Conclusion: The survey reveals a wide range of ASP development in Asia Pacific. Establishing national workgroups and guidelines will help advance antimicrobial stewardship in this diverse region.

Waning humoral immunity after mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a significant problem for public health. Breakthrough infection in hospitals over several months after vaccination has not been fully characterized, especially against the delta (B.1.617.2) variant. Here, we describe an outbreak in our hospital in September of 2021, mainly through serological evaluation of the breakthrough infection. This retrospective observational study was done at an emergency and acute care hospital with 204 beds and 486 staff members where most staff members (92.6%) had had their second BNT162b2 vaccination by May of 2021. The peri-infection anti-spike RBD protein IgG (anti-S IgG) titers (lowest values between 11 days before and 7 days after onset or diagnosis) of serum samples from the breakthrough-infected persons were quantified. We also logarithmically estimated the anti-S IgG titers during the exposure period in September of uninfected staff members from their samples collected in May and December 2021. Whole-genome sequencing was done on obtained samples. In this outbreak, twelve persons (ten inpatients and two staff members) were diagnosed with SARS-CoV-2 infection by Loop-Mediated Isothermal Amplification (LAMP) or RT-PCR, eight of whom had been vaccinated twice. Peri-infection anti-S IgG titers could be determined in seven of the eight breakthrough cases, with a geometric mean titer (GMT) of 1,034 AU/ml (95% confidence interval [CI], 398 to 2,686). Among 289 uninfected staff members with data from the two sampling points, the GMT of the estimated anti-S IgG titers during the exposure period in 51 staff members, who were working at the outbreak ward and potentially exposed but uninfected, and 238 other unexposed staff members were 1,458 AU/ml (95% CI, 1,196 to 1,777) and 1,628 AU/ml (95% CI, 1,500 to 1,766), respectively. All viruses from the eight samples for which whole-genome sequencing was available were identified as delta variants. Of the infected persons, one remained asymptomatic throughout the course of treatment, and eleven had an illness of mild to moderate severity, including ten who received monoclonal antibody cocktail (Casirivimab/imdevimab) therapy. Measurement and estimation of anti-spike antibody levels after SARS-CoV-2 vaccination would be helpful for evaluating the risk of breakthrough infection and for determining the necessity of booster vaccination.

The coronavirus disease 2019 (COVID-19) global pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains uncontrolled, with the spread of emerging variants. According to accumulating evidence, diabetes is one of the leading risk factors for a severe COVID-19 clinical course, depending on the glycemic state before admission and during COVID-19 hospitalization. Multiple factors are thought to be responsible, including an altered immune response, coexisting comorbidity, and disruption of the renin-angiotensin system through the virus–host interaction. However, the precise underlying mechanisms remain under investigation. Alternatively, the focus is currently on the diabetogenic and ketosis-prone potential of SARS-CoV-2 itself, even for probable triggers of stress and steroid-induced hyperglycemia in COVID-19. In this article, we present a comprehensive review of the recent literature on the clinical and experimental findings associated with diabetes and COVID-19, and we discuss their bidirectional relationship, i.e., the risk for an adverse prognosis and the deleterious effects on glycometabolism. Accurate assessments of the incidence of new-onset diabetes induced by COVID-19 and its pathogenicity are still unknown, especially in the context of the circulation of SARS-CoV-2 variants, such as Omicron (B.1.1.529), which is a major challenge for the future.

Abstract Background Invasive Meningococcal Disease (IMD) is a rare and critical disease in Japan. Most of these cases are caused by capsulated Neisseria meningitidis strains. Non-capsulated (non-typable) strains are considered relatively low-pathogenic and can colonize in the nasopharynx of healthy children and young adults. As far as could be ascertained, only twelve IMD cases due to non-capsulated strains have been reported in the literature. No clear risk factors could be identified in a literature review (unknown or immunocompetent, seven cases; C6 deficiency, three cases). Case presentation We report a Japanese male taxi driver with bacteremia and meningitis due to non-capsulated N. meningitidis. He had a fever and shaking chills. Ceftriaxone was administered, and the patient finally recovered. During the clinical course, relative adrenal insufficiency occurred and was treated with hydrocortisone. A hidden co-morbidity, immunoglobulin G4 (IgG4)-related disease, was revealed in the past surgical history (a resection of bilateral orbital tumors), which included symptoms (swelling lachrymal glands and lymph nodes), elevated IgG4, immunoglobulin E, and hypocomplementemia. He recovered finally and no recurrence was observed. Conclusions Our IMD case is the first reported in Japan, where IMD is not considered pandemic. The patient had a history of IgG4-related disease, although we could not establish a clear relationship between the patient’s IMD and co-morbidity. A collection of further clinical cases might establish the risk factors and characteristics of IMD that could be caused by this neglected pathogen, non-capsulated N. meningitidis.

Stenotrophomonas maltophilia is an important nosocomial bacterial pathogen, as is Pseudomonas aeruginosa. Differentiation of these bacteria as bacteremic agents is critical in the clinical setting and to define a therapeutic strategy; however, the associated factors and prognosis for S. maltophilia bacteremia have not been fully evaluated to adequately characterize these factors. We first conducted a matched case-control study to clarify these questions. A total of 30 case patients with S. maltophilia bacteremia were compared with 30 control patients with P. aeruginosa bacteremia between January 2005 and August 2014, according to matching criteria based on underlying disease, age, and gender. The 30-day mortality rate for the case patients (53.3%) was significantly higher than that of the control group (30.0%) (P = 0.047, using the log-rank test). Conditional logistic regression analysis showed that the predisposing factors specific for the detection of S. maltophilia bacteremia were indwelling artificial products other than a central venous catheter, ICU stay, and previous use of anti-MRSA drugs. The high severity of illness was associated with mortality in both case and control patients. Interestingly, inappropriate antimicrobial treatment was an additional independent risk factor for mortality in only the case patients with S. maltophilia bacteremia (odds ratio = 13.64, P = 0.048). Monotherapy with fluoroquinolones inactive against the S. maltophilia isolates was mainly responsible for the inappropriate treatment. These results suggest that more precise prediction and more appropriate treatment might improve the prognosis of patients with S. maltophilia bacteremia.

BACKGROUND: Fluoroquinolone prophylaxis in patients with neutropenia and hematological malignancies is said to be effective on febrile netropenia (FN)-related infection and mortality; however, the emergence of antibiotic resistance has become a concern. Ciprofloxacin and levofloxacin prophylaxis are most commonly recommended. A significant increase in the rate of quinolone-resistant Escherichia coli in fecal flora has been reported following ciprofloxacin prophylaxis. The acquisition of quinolone-resistant E. coli after levofloxacin use has not been evaluated. METHODS: We prospectively examined the incidence of quinolone-resistant E. coli isolates recovered from stool cultures before and after levofloxacin prophylaxis in patients with neutropenia from August 2011 to May 2013. Some patients received chemotherapy multiple times. RESULTS: In this trial, 68 patients were registered. Levofloxacin-resistant E. coli isolates were detected from 11 and 13 of all patients before and after the prophylaxis, respectively. However, this was not statistically significant (P = 0.65). Multiple prophylaxis for sequential chemotherapy did not induce additional quinolone resistance among E. coli isolates. Interestingly, quinolone-resistant E. coli, most of which were extended-spectrum β-lactamase (ESBL) producers, were already detected in approximately 20% of all patients before the initiation of prophylaxis. FN-related bacteremia developed in 2 patients, accompanied by a good prognosis. CONCLUSIONS: Levofloxacin prophylaxis for neutropenia did not result in a significant acquisition of quinolone-resistant E. coli. However, we detected previous colonization of quinolone-resistant E. coli before prophylaxis, which possibly reflects the spread of ESBL. The epidemic spread of resistant E. coli as a local factor may influence strategies toward the use of quinolone prophylaxis.

BACKGROUND: Our unit adopted the single administration of cefepime as the initial treatment for febrile episodes in neutropenic patients with hematological malignancies. However, recently, cefepime-resistant gram-negative bacteremia, including those with extended-spectrum β-lactamase (ESBL)-producers, was frequently observed in these patients. Therefore, we instituted a rotation of primary antibiotics for febrile neutropenic patients in an attempt to control antibiotic resistance. METHODS: This prospective trial was performed from August 2008 through March 2011 at our unit. After a pre-intervention period, in which cefepime was used as the initial agent for febrile neutropenia, 4 primary antibiotics, namely, piperacillin-tazobactam, ciprofloxacin, meropenem, and cefepime, were rotated at 1-month intervals over 20 months. Blood and surveillance cultures were conducted for febrile episodes, in order to assess the etiology, the resistance pattern (particularly to cefepime), and the prognosis. RESULTS: In this trial, 219 patients were registered. A 65.9% reduction in the use of cefepime occurred after the antibiotic rotation. In the surveillance stool cultures, the detection rate of cefepime-resistant gram-negative isolates, of which ESBL-producers were predominant, declined significantly after the intervention (8.5 vs 0.9 episodes per 1000 patient days before and after intervention respectively, P