Outbreak investigation of Serratia marcescens bloodstream infection in an obstetric ward for high-risk pregnant women.

BACKGROUND: Serratia marcescens is a gram-negative bacterium that is widespread in the environment. S. marcescens bacteremia can be fatal during pregnancy and cause persistent chorioamnionitis. This study reports an outbreak of Serratia marcescens bloodstream infection (BSI) among high-risk pregnant women in an obstetric ward. The purpose of this study is to report our experience with the usefulness of the ATP test in hospital environmental management and to confirm that bloodstream infections of patients with the same strain were correlated by WGS testing. METHODS: This retrospective study collected the data of inpatients with S. marcescens bacteremia in obstetric ward for high-risk pregnant women from August 22, 2021, to October 14, 2021. We performed: an adenosine triphosphate (ATP) bioluminescence test in the environment with a high-contact area; environmental culture; on-site monitoring and staff education; and whole-genome sequencing (WGS) to evaluate genetic relationships among S. marcescens isolates. RESULTS: S. marcescens BSI occurred in four consecutive patients. None of the patients had central venous catheters. An ATP bioluminescence test revealed that high-contact areas and areas for injection preparation were not clean (≥ 1000 relative light units). However, S. marcescens was not identified in the environmental cultures, likely due to intensive environmental cleaning and discarding of potentially contaminated specimens before the culture test. On-site monitoring and education were conducted for 1 month. There were no further reports of BSI until 6 months after the last patient was discharged. WGS performed on three isolates from three patients indicated that the isolated S. marcescens was likely from the same strain. CONCLUSIONS: We controlled an S. marcescens outbreak by improving environmental cleaning as well as education of and behavior changes in healthcare workers. Using the ATP bioluminescence test can provide feedback on environmental cleaning and education. WGS played a role in determining the spread of BSI caused by the same strain.

The relationship between organising pneumonia and invasive mould disease in patients with haematologic malignancy.

BACKGROUND: Organising pneumonia (OP) is reported in patients with haematologic malignancy suspected of having invasive mould disease, yet little is known about this relationship. OBJECTIVE: To investigate molecular evidence of invasive mould pneumonia in paraffin-embedded lung tissues from histologically diagnosed OP patients with suspected invasive mould pneumonia. PATIENTS/METHODS: Patients with haematologic malignancy suspected to have invasive pulmonary mould disease who underwent lung biopsy at a tertiary hospital, Seoul, South Korea, between 2008 and 2020, were retrospectively reviewed. To find molecular evidence of fungal infection, PCR assay was used to detect Aspergillus- and Mucorales-specific DNA within OP lung tissue sections. RESULTS: Forty-seven patients with suspected invasive mould pneumonia underwent lung biopsy and 15 (32%) were histologically diagnosed as OP without any evidence of fungal hyphae. Of these 15 patients, 3 (20%) received allogenic haematopoietic stem cell transplantation prior to developing OP. Before biopsy, 2 and 13 patients had probably and possible invasive mould disease, respectively. The median antifungal treatment length was 81 [8-114] days, and the median steroid treatment dosage was 0.35 mg/kg/day for 36 days (methylprednisolone equivalent doses), respectively. After biopsy, three patients with possible invasive mould infection revealed probable invasive pulmonary aspergillosis. From the 15 paraffin-embedded lung tissues, 6 (40%) exhibited positive PCR assay results for detecting Aspergillus- and Mucorales-specific DNA. CONCLUSIONS: More than one third of OP cases in patients with suspected invasive mould pneumonia exhibited molecular evidence of invasive mould infection by fungus-specific PCR in lung tissues, likely associated with concurrent or prior fungal infection.

Pneumocystis jirovecii Pneumonia in Patients with Solid Malignancies: A Retrospective Study in Two Hospitals.

Pneumocystis jirovecii pneumonia (PJP) is a rare opportunistic infection in patients with solid malignancies. This study aimed to examine the characteristics of patients with solid cancers and PJP. We retrospectively reviewed the medical records of patients with solid tumors and PJP over an 11-year period, enrolling a total of 47 patients (30-day survival group: n = 20, 30-day mortality group: n = 27). Only 34% of patients received ≥20 mg of prednisolone for ≥2 weeks, and the 30-day mortality rate was 57.4%. The 30-day survival group included more women and patients with colon cancer than the mortality group. Furthermore, absolute lymphocyte counts (ALCs) were decreased at PJP symptom onset, as compared with the values observed 1-3 months earlier. Increased oxygen demand and low ALCs after 5-7 days of PJP treatment were also related to poor prognosis. Due to the limitations of this retrospective study, further studies that adhere to the PJP criteria of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium will be needed to evaluate PJP in solid malignancies more clearly.

In Vitro Activities of Ceftazidime-Avibactam and Aztreonam-Avibactam at Different Inoculum Sizes of Extended-Spectrum ß-Lactam-Resistant Enterobacterales Blood Isolates.

ß-lactam-avibactam combinations have been proposed as carbapenem-sparing therapies, but little data exist on their in vitro activities in infections with high bacterial inocula. We investigated the in vitro efficacies and the inoculum effects of ceftazidime-avibactam and aztreonam-avibactam against extended-spectrum ß-lactam-resistant Enterobacterales blood isolates. A total of 228 non-repetitive extended-spectrum ß-lactam-resistant Escherichia coli and Klebsiella pneumoniae blood isolates were prospectively collected in a tertiary center. In vitro susceptibilities to ceftazidime, aztreonam, meropenem, ceftazidime-avibactam, and aztreonam-avibactam were evaluated by broth microdilution method using standard and high inocula. An inoculum effect was defined as an eightfold or greater increase in MIC when tested with the high inoculum. Of the 228 isolates, 99% were susceptible to ceftazidime-avibactam and 99% had low aztreonam-avibactam MICs (≤8 mg/L). Ceftazidime-avibactam and aztreonam-avibactam exhibited good in vitro activities; MIC50/MIC90 values were 0.5/2 mg/L, 0.125/0.5 mg/L, and ≤0.03/0.25 mg/L, respectively, and aztreonam-avibactam was more active than ceftazidime-avibactam. The frequencies of the inoculum effect with ceftazidime-avibactam and aztreonam-avibactam were lower than with meropenem (14% vs. 38%, p < 0.001 and 30% vs. 38%, p = 0.03, respectively). The ß-lactam-avibactam combinations could be useful as carbapenem-sparing strategies, and aztreonam-avibactam has the better in vitro activity but is more subject to the inoculum effect than ceftazidime-avibactam.

Molecular diagnosis of Coxiella burnetii in culture negative endocarditis and vascular infection in South Korea.

BACKGROUND: Q fever endocarditis is a major cause of culture-negative endocarditis. The role of Coxellia burnetii is underestimated because it is difficult to diagnose. We investigated the significance of C. burnetii as the cause of culture-negative endocarditis and vascular infection by examining blood and tissue specimens using serological testing and polymerase chain reaction (PCR). METHODS: All patients with infective endocarditis or large vessel vasculitis were prospectively enrolled at a tertiary-care hospital from May 2016 through September 2020. Q fever endocarditis and vascular infection were diagnosed based on: (1) positive PCR for a cardiac valve or vascular tissue, (2) positive PCR for blood or phase I immunoglobulin G (IgG) ≥ 6400, or (3) phase I IgG ≥ 800 and < 6400 with morphologic abnormality. PCR targeted C. burnetii transposase gene insertion element IS1111a. RESULTS: Of the 163 patients, 40 (25%) had culture-negative endocarditis (n = 35) or vascular infection (n = 5). Of the 40 patients, 24 (60%) were enrolled. Eight (33%) were diagnosed with Q fever endocarditis or vascular infection. Of these 8 patients, 6 had suspected acute Q fever endocarditis or vascular infection with negative phase I IgG. Six patients were not treated for C. burnetii, 4 were stable after surgery. One patient died due to surgical site infection after 5 months post-operatively and one died due to worsening underlying disease. CONCLUSIONS: Approximately one-third of patients with culture-negative endocarditis and vascular infection was diagnosed as Q fever. Q fever endocarditis and vascular infection may be underestimated in routine clinical practice in South Korea.KEY MESSAGEQ fever endocarditis and vascular infection may be underestimated in routine clinical practice, thus, try to find evidence of C. burnetti infection in suspected patients by all available diagnostic tests including PCR.

Short versus prolonged courses of antimicrobial therapy for patients with uncomplicated Pseudomonas aeruginosa bloodstream infection: a retrospective study.

BACKGROUND: The optimal duration of antimicrobial therapy for uncomplicated Pseudomonas aeruginosa bloodstream infection (BSI) is unknown. We compared the outcomes of short and prolonged courses of antimicrobial therapy in adults with uncomplicated pseudomonal BSI. METHODS: All patients with uncomplicated P. aeruginosa BSI admitted at a tertiary-care hospital from April 2010 to April 2020 were included. We compared the primary outcome (a composite of the rate of recurrent P. aeruginosa infection and mortality within 30 days after discontinuing antimicrobial therapy) among patients who underwent short (7‒11 days) and prolonged (12‒21 days) courses of antimicrobial therapy using propensity score analysis with the inverse probability of treatment weighting (IPTW) method. RESULTS: We evaluated 1477 patients with P. aeruginosa BSI; of them, 290 met the eligibility criteria who received antimicrobial agents with in vitro activity, including 97 (33%) who underwent short-course therapy [median of 9 (IQR = 8‒11) days] and 193 (67%) who underwent prolonged-course therapy [median of 15 (IQR = 14‒18) days]. We found no significant difference in the risk of recurrence or 30 day mortality between the prolonged-course and short-course groups [n = 30 (16%) versus n = 11 (11%); IPTW-adjusted HR = 0.68, 95% CI = 0.34 - 1.36, P = 0.28]. The prolonged-course therapy did not significantly reduce the risk of the recurrence of P. aeruginosa infection within 180 days compared with short-course therapy [n = 37 (19%) versus n = 12 (12%); IPTW-adjusted HR = 0.57, 95% CI = 0.29 - 1.10, P = 0.09]. CONCLUSIONS: Short-course antimicrobial therapy could be as effective as prolonged-course therapy for uncomplicated P. aeruginosa BSI.

In Vitro Activities and Inoculum Effects of Ceftazidime-Avibactam and Aztreonam-Avibactam against Carbapenem-Resistant Enterobacterales Isolates from South Korea.

Ceftazidime-avibactam (CAZ-AVI) and aztreonam-avibactam (AZT-AVI) are novel antibiotic combinations active against multidrug-resistant Gram-negative pathogens. This study aimed to evaluate their in vitro activities and inoculum effects in carbapenem-resistant Enterobacterales (CRE), including carbapenemase-producing (CP)-CRE and non-CP-CRE. A total of 81 independent clinical isolates of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae were collected. CAZ-AVI and AZT-AVI minimal inhibitory concentrations (MICs) were evaluated by broth microdilution using standard and high inocula. The inoculum effect was defined as an ≥8-fold increase in MIC with high inoculum. Phenotypic determination of ß-lactam resistance mechanism and PCR for carbapenemase genes were performed. Of the 81 CRE isolates, 35 (43%) were CP-CRE. Overall, 73% of the isolates were susceptible to CAZ-AVI, and 95% had low AZT-AVI MICs (≤8 µg/mL). The MIC50/MIC90s of CAZ-AVI and AZT-AVI were 4/≥512 µg/mL and 0.5/4 µg/mL, respectively. CAZ-AVI was more active against non-CP-CRE than against CP-CRE (susceptibility 80% vs. 63%, p = 0.08; MIC50/MIC90, 2/16 µg/mL vs. 4/≥512 µg/mL), whereas AZT-AVI was more active against CP-CRE (MIC50/MIC90, 0.25/1 µg/mL vs. 0.5/8 µg/mL). All four isolates with high AZT-AVI MIC (≥16 µg/mL) were resistant to CAZ-AVI, but only 18% (4/22) of CAZ-AVI-resistant isolates had high AZT-AVI MIC. The rates of the inoculum effect for CAZ-AVI and AZT-AVI were 18% and 47%, respectively (p < 0.001). Interestingly, the frequency of the AZT-AVI inoculum effect was higher in K. pneumoniae than E. coli (64% vs. 8%, p < 0.001). AZT-AVI is more active against CRE than CAZ-AVI, even in CP-CRE and CAZ-AVI-resistant isolates. The presence of a substantial inoculum effect may contribute to clinical failure in high-inoculum infections treated with AZT-AVI.

Infections in Lung Transplant Recipients during and after Prophylaxis.

BACKGROUND: The timeline of infections after lung transplantation has been changed with the introduction of new immunosuppressants and prophylaxis strategies. The study aimed to investigate the epidemiological characteristics of infectious diseases after lung transplantation in the current era. MATERIALS AND METHODS: All patients who underwent lung or heart-lung transplantation at our institution between October 29, 2008 and April 3, 2019 were enrolled. We retrospectively reviewed the patients' medical records till April 2, 2020. RESULTS: In total, 100 consecutive lung transplant recipients were enrolled. The median follow-up period was 28 months after lung transplantation. A total of 127 post-lung transplantation bacterial infections occurred. Catheter-related bloodstream infection (25/84, 29.8%) was the most common within 6 months and pneumonia (23/43, 53.5%) was the most common after 6 months. Most episodes (35/40, 87.5%) of respiratory viral infections occurred after 6 months, mainly as upper respiratory infections. The remaining episodes (5/40, 12.5%) mostly manifested as lower respiratory tract infections. Seventy cytomegalovirus infections observed in 43 patients were divided into 23 episodes occurring before and 47 episodes occurring after discontinuing prophylaxis. Of 10 episodes of cytomegalovirus disease, four occurred during prophylaxis and six occurred after prophylaxis. Of 23 episodes of post-lung transplantation fungal infection, 7 were aspergillosis and all occurred after the discontinuation of prophylaxis. CONCLUSION: Lung transplant recipients experienced a high burden of infection even after 6 months, especially after the end of the prophylaxis period. Therefore, these patients should be continued to be monitored long-term for infectious disease.

Clinical and Microbiological Analysis of Risk Factors for Mortality in Patients With Carbapenem-Resistant Acinetobacter baumannii Bacteremia.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is associated with significant mortality, causing worldwide concern, yet there are limited data on contributing microbiological factors. This study aimed to identify the clinical and microbiologic risk factors for mortality in CRAB bacteremia. METHODS: Adult patients with monomicrobial CRAB bacteremia in a 2700-bed tertiary hospital between December 2012 and December 2018 were retrospectively enrolled. Risk factors for 30-day mortality were evaluated. All isolates collected on the first day of bacteremia were subjected to colistin susceptibility testing by broth microdilution and to genotyping by multilocus sequence typing. RESULTS: A total of 164 patients were enrolled, and 90 (55%) died within 30 days. The most common genotype among the isolates was ST191 (49%), and 12 isolates (7%) were resistant to colistin. Genotype, colistin minimum inhibitory concentration, and colistin resistance were not significantly associated with mortality, in contrast to several clinical factors. In multivariable analysis, ineradicable or not-eradicated focus (adjusted odds ratio [aOR], 4.92; 95% CI, 1.95-12.42; P = .001), septic shock (aOR, 4.72; 95% CI, 2.12-10.49; P < .001), and inappropriate antimicrobial therapy (aOR, 2.54; 95% CI, 1.05-6.16; P = .04) were independent risk factors for mortality. Among antibiotic strategies, colistin combined with tigecycline or other antibiotics were significantly associated with lower mortality after adjustment for confounding factors. CONCLUSIONS: Clinical factors such as the nature of the infection source and source control, severity of bacteremia, and appropriateness of antibiotics, rather than microbiological factors, contribute to mortality in CRAB bacteremia. A specific antibiotic combination may help improve outcomes.

Importance of Follow-Up Microscopic Examination in Hospitalized Patients with Confirmed Scabies.

We investigated the duration of positive microscopic examination in hospitalized patients with confirmed scabies in an acute care hospital. We included hospitalized patients who were diagnosed with scabies between January 2015 and June 2019. From the study period, a total of 31 patients with confirmed scabies were identified. Median age was 75 years. Of a total of 31 patients with confirmed scabies, six were discharged or transferred before getting a negative microscopic test result. Of the remaining 25 patients with negative microscopic test results, the median duration from diagnosis to a negative microscopic test result was 14 days (interquartile range, 9-17). Given that nosocomial outbreaks lead to high workload and considerable resource consumption, adequate treatment, sufficient follow-up examination, and confirmation of cure are warranted before releasing contact isolation.

Diagnostic value of the molecular detection of Sarcoptes scabiei from a skin scraping in patients with suspected scabies.

Scabies is a highly contagious parasitic disease associated with long-term residence in nursing homes, and it is a public health burden worldwide. However, atypical skin manifestations are frequent and the widely used diagnostic test based on microscopic examinations has limited sensitivity. We evaluated the diagnostic value of polymerase chain reaction (PCR) from skin scraping in patients with suspected scabies. Adult patients with suspected scabies, unrelated diseases or healthy volunteers were enrolled at a tertiary hospital, in Seoul, South Korea, from December 2017 through October 2018. We classified participants based on the consensus criteria established by the International Alliance for the Control of Scabies in 2018; confirmed (microscopic mite detection), clinical (scabies burrow or typical lesions with two history features including itch and close contact with scabies patients), suspected scabies (typical lesion with one history feature or atypical lesion with two history features), or no scabies. PCR was performed on the skin scrapings to target the cytochrome c oxidase subunit 1 (cox1) gene of Sarcoptes scabiei. A total of 47 participants, 33 with suspected scabies, 10 with unrelated diseases, and 4 healthy volunteers were enrolled. Of the 33 patients, 22 were classified as confirmed scabies, 2 as clinical scabies, 6 as suspected scabies, and 3 as no scabies. The sensitivities of the microscopic examination were 100%, 92%, and 73% in confirmed scabies; confirmed and clinical scabies; and confirmed, clinical, and suspected scabies, respectively (p = 0.006). The sensitivities of PCR were 86%, 83%, and 80% in confirmed scabies; confirmed and clinical scabies; and confirmed, clinical, and suspected scabies, respectively (p = 0.59). The specificity of the scabies PCR in the no scabies control was 100% (95% CI = 80-100).PCR testing for scabies may be helpful in the improvement of sensitivity for the diagnosis of scabies by clinical criteria.

Detection of Coxiella burnetii Using Silicon Microring Resonator in Patient Blood Plasma.

Blood plasma from patients is a powerful resource for diagnosing infectious disease due to it having many genetic materials as well as being relatively easy to obtain. Thus, various biosensors have been investigated for diagnosing diseases in blood plasma. However, there are no optimized and validated sensors for clinical use due to the low sensitivity, complexity, and difficulties of removing the inhibitors from plasma samples. In this study, we described a silicon microring resonator sensor used to detect Coxiella burnetii from the blood plasma of Q-fever patients in a label-free, real-time manner. Q-fever is an infectious disease caused by Coxiella burnetii via direct contact or inhalation aerosols. We validated this biosensor in the blood plasma of 35 clinical samples (including 16 Q fever samples infected with Coxiella burnetii and 19 samples infected with other febrile diseases. The biosensors are capable of rapid (10 min), highly sensitive (87.5%), and specific (89.5%) detection in plasma samples compared to the use of the conventional method.

Diagnostic usefulness of molecular detection of Coxiella burnetii from blood of patients with suspected acute Q fever.

Diagnosis of Q fever is difficult due to the lack of distinct clinical features that distinguish it from other febrile diseases. Serologic testing is the gold standard method for diagnosing Q fever, but antibody formation may not be detectable for 2 to 3 weeks from symptom onset, limiting early diagnosis. We thus evaluated the diagnostic utility of polymerase chain reaction (PCR) to detect Coxellia burnetii DNA in serum from patients with suspected acute Q fever.All adult patients with suspected acute Q fever were prospectively enrolled at a tertiary-care hospital from January 2016 through July 2018. Acute Q fever was diagnosed using clinical and laboratory criteria: fever with at least one other symptoms (myalgia, headache, pneumonia, or hepatitis) and single phase II immunoglobulin G (IgG) antibody titers ≥1:200 or immunoglobulin M (IgM) antibody titer ≥1:50 (probable), or a fourfold increase or seroconversion in phase II IgG antibody titers as measured by indirect immunofluorescence assays between paired samples (confirmed). We performed PCR targeting the transposase gene insertion element IS1111a of C. burnetii.Of the 35 patients with suspected acute Q fever, 16 (46%) were diagnosed with acute Q fever including 8 probable and 8 confirmed cases; the remaining 19 (54%) were diagnosed with other febrile diseases. The proportion of males diagnosed with Q fever was higher than those diagnosed with other febrile diseases (88% vs 44%, P = .03), but there were no other significant differences in clinical characteristics between the 2 groups. The Q fever PCR sensitivity was 81% (95% confidence interval [CI], 54-96), specificity was 90% (95% CI, 67-99), positive predictive value was 87% (95% CI, 63-96), and negative predictive value was 85% (95% CI, 67-94).Q fever PCR testing using blood from patients with suspected acute Q fever seems to be a rapid and useful test for early diagnosis of Q fever.

Clinical Characteristics and Radiologic Features of Immunocompromised Patients With Pauci-Bacillary Pulmonary Tuberculosis Receiving Delayed Diagnosis and Treatment.

BACKGROUND: Pauci-bacillary pulmonary tuberculosis (TB) can be delayed to diagnose and start anti-TB therapy, especially in immunocompromised patients. We therefore evaluated the clinical and radiologic features of these delayed cases. METHODS: Immunocompromised adult patients with pauci-bacillary pulmonary TB were retrospectively enrolled in a tertiary hospital in an intermediate-TB burden country over a 5-year period. We defined "missed TB" or "not-missed TB" patients as those who started anti-TB therapy after or before positive mycobacterial culture results, respectively. RESULTS: Of 258 patients, 134 (52%) were classified in the missed TB group, and 124 (48%) in the not-missed TB group. Positive results of molecular tests including MTB polymerase chain reaction and/or Xpert TB/RIF were only obtained in the not-missed TB group (54/106, 54%). The median diagnostic delay in the missed TB group was longer than in the other group (30 vs 6 days; P < .001). In the missed TB group, the most common working diagnoses were pneumonia (46, 34%) and lung metastasis of malignancy (40, 30%). Typical radiologic findings for TB, such as upper lobe predominance and centrilobular nodules with tree-in-bud appearance, were less common in the missed TB group than in the other group. Old age (odds ratio [OR], 1.03), solid organ transplant (OR, 3.46), solid tumor (OR, 3.83), and hematologic malignancy (OR, 4.04) were independently associated with missed TB. CONCLUSIONS: Care is needed to differentiate pauci-bacillary TB, especially in immunocompromised patients with the mentioned risk factors, even without the usual radiologic features of TB. Additional rapid diagnostic tests to rule out pauci-bacillary TB are urgently needed.

Improvement of blood culture contamination rate, blood volume, and true positive rate after introducing a dedicated phlebotomy team.

The introduction of dedicated phlebotomy teams certified for blood collection has been reported to be highly cost-effective by reducing contamination rates. However, data on their effects on blood volume and true positive rate are limited. Therefore, we investigated the effect of replacing interns with a phlebotomy team on blood culture results. We performed a 24-month retrospective, quasi-experimental study before and after the introduction of a phlebotomy team dedicated to collecting blood cultures in a 2700-bed tertiary-care hospital. The microbiology laboratory database was used to identify adult patients with positive blood culture results. During the study period, there were no changes in blood collection method, blood culture tubes, and the application of antiseptic measures. Blood volume was measured by the BACTEC™ FX system based on red blood cell metabolism. A total of 162,207 blood cultures from 23,563 patients were analyzed, comprising 78,673 blood cultures during the intern period and 83,534 during the phlebotomy team period. Blood volume increased from a mean of 2.1 ml in the intern period to a mean of 5.6 ml in the phlebotomy team period (p < 0.001). Introduction of the phlebotomy team also reduced contamination rate (0.27% vs. 0.45%, p < 0.001) and led to a higher true positive rate (5.87% vs. 5.01%, p < 0.05). The increased true positive rate associated with the phlebotomy team involved both gram-positive and gram-negative bacteria. The introduction of a dedicated phlebotomy team can increase blood volumes, reduce blood culture contamination rate, and increase true positive rate.