Biocide resistance in Klebsiella pneumoniae: a narrative review.

Klebsiella pneumoniae is among the World Health Organization's list of priority pathogens, notorious for its role in causing healthcare-associated infections and neonatal sepsis globally. Containment of K. pneumoniae transmission depends on the continued effectiveness of antimicrobials and of biocides used for topical antisepsis and surface disinfection. Klebsiella pneumoniae is known to disseminate antimicrobial resistance (AMR) through a large auxiliary genome made up of plasmids, transposons and integrons, enabling it to evade antimicrobial killing through the use of efflux systems and biofilm development. Because AMR mechanisms are also known to impart tolerance to biocides, AMR is frequently linked with biocide resistance (BR). However, despite extensive research on AMR, there is a gap in knowledge about BR and the extent to which AMR and BR mechanisms overlap remains debatable. The aim of this paper is to review and summarise the current knowledge on the determinants of BR in K. pneumoniae and highlight content areas that require further inquiry.

Antibiotic Use for Sepsis in Hospitalized Neonates in Botswana: Factors Associated with Guideline-Divergent Prescribing.

In low- and middle-income countries, where antimicrobial access may be erratic and neonatal sepsis pathogens are frequently multidrug-resistant, empiric antibiotic prescribing practices may diverge from the World Health Organization (WHO) guidelines. This study examined antibiotic prescribing for neonatal sepsis at a tertiary referral hospital neonatal unit in Gaborone, Botswana, using data from a prospective cohort of 467 neonates. We reviewed antibiotic prescriptions for the first episode of suspected sepsis, categorized as early-onset (EOS, days 0-3) or late-onset (LOS, >3 days). The WHO prescribing guidelines were used to determine whether antibiotics were "guideline-synchronous" or "guideline-divergent". Logistic regression models examined independent associations between the time of neonatal sepsis onset and estimated gestational age (EGA) with guideline-divergent antibiotic use. The majority (325/470, 69%) were prescribed one or more antibiotics, and 31 (10%) received guideline-divergent antibiotics. Risk factors for guideline-divergent prescribing included neonates with LOS, compared to EOS (aOR [95% CI]: 4.89 (1.81, 12.57)). Prematurity was a risk factor for guideline-divergent prescribing. Every 1-week decrease in EGA resulted in 11% increased odds of guideline-divergent antibiotics (OR [95% CI]: 0.89 (0.81, 0.97)). Premature infants with LOS had higher odds of guideline-divergent prescribing. Studies are needed to define the causes of this differential rate of guideline-divergent prescribing to guide future interventions.

Healthcare-Associated Infection Prevention Interventions for Neonates in Resource-Limited Settings.

Healthcare-associated infections (HAIs) and antimicrobial-resistant (AMR) infections are leading causes of neonatal morbidity and mortality, contributing to an extended hospital stay and increased healthcare costs. Although the burden and impact of HAI/AMR in resource-limited neonatal units are substantial, there are few HAI/AMR prevention studies in these settings. We reviewed the mechanism of action and evidence supporting HAI/AMR prevention interventions, including care bundles, for hospitalized neonates in low- and middle-income countries (LMIC).

Keeping It Real: Infection Prevention and Control Problems and Solutions in Low- and Middle-income Countries.

Infection prevention challenges are ubiquitous in healthcare, but some are unique to or more prevalent in low-and middle-income country settings. Despite limited resources, innovative and committed paediatric healthcare providers and infection preventionists have found creative solutions to address the very real and pressing risks their patients face every day. We gathered examples of infection prevention and control challenges faced by clinicians in resource-limited healthcare facilities, and the real-world infection prevention and control solutions they implemented, with the goal of learning broader lessons applicable to low-and middle-income countrie.

Characterizing the bioburden of ESBL-producing organisms in a neonatal unit using chromogenic culture media: a feasible and efficient environmental sampling method.

INTRODUCTION: Infections due to extended spectrum beta-lactamase producing organisms (ESBL) have emerged as the leading cause of sepsis among hospitalized neonates in Botswana and much of sub-Saharan Africa and south Asia. Yet, ESBL reservoirs and transmission dynamics within the neonatal intensive care unit (NICU) environment are not well-understood. This study aimed to assess the efficiency and feasibility of a chromogenic-culture-media-based environmental sampling approach to characterize the ESBL bioburden within a NICU. METHODS: A series of four point-prevalence surveys were conducted at a 36-bed NICU at a public tertiary referral hospital in Botswana from January-June 2021. Samples were collected on 4 occasions under semi-sterile technique using 1) flocked swabs & templates (flat surfaces); 2) sterile syringe & tubing (water aspiration); and 3) structured swabbing techniques (hands & equipment). Swabs were transported in physiological saline-containing tubes, vortexed, and 10 µL was inoculated onto chromogenic-agar that was selective and differential for ESBL (CHROMagar™ ESBL, Paris, France), and streaking plates to isolate individual colonies. Bacterial colonies were quantified and phenotypically characterized using biochemical identification tests. RESULTS: In total, 567 samples were collected, 248 (44%) of which grew ESBL. Dense and consistent ESBL contamination was detected in and around sinks and certain high-touch surfaces, while transient contamination was demonstrated on medical equipment, caregivers/healthcare worker hands, insects, and feeding stations (including formula powder). Results were available within 24-72 h of collection. To collect, plate, and analyse 50 samples, we estimated a total expenditure of $269.40 USD for materials and 13.5 cumulative work hours among all personnel. CONCLUSIONS: Using basic environmental sampling and laboratory techniques aided by chromogenic culture media, we identified ESBL reservoirs (sinks) and plausible transmission vehicles (medical equipment, infant formula, hands of caregivers/healthcare workers, & insects) in this NICU environment. This strategy was a simple and cost-efficient method to assess ESBL bioburden and may be feasible for use in other settings to support ongoing infection control assessments and outbreak investigations.

Azithromycin and Ciprofloxacin Treatment Outcomes During an Outbreak of Multidrug-Resistant Shigella sonnei Infections in a Retirement Community-Vermont, 2018.

BACKGROUND: In 2018, the Centers for Disease Control and Prevention and the Vermont Department of Health investigated an outbreak of multidrug-resistant Shigella sonnei infections in a retirement community that offered a continuum of care from independent living through skilled nursing care. The investigation identified 24 culture-confirmed cases. Isolates were resistant to trimethoprim-sulfamethoxazole, ampicillin, and ceftriaxone, and had decreased susceptibility to azithromycin and ciprofloxacin. METHODS: To evaluate clinical and microbiologic response, we reviewed inpatient and outpatient medical records for treatment outcomes among the 24 patients with culture-confirmed S. sonnei infection. We defined clinical failure as diarrhea (≥3 loose stools per day) for ≥1 day after treatment finished, and microbiologic failure as a stool culture that yielded S. sonnei after treatment finished. We used broth microdilution to perform antimicrobial susceptibility testing, and whole genome sequencing to identify resistance mechanisms. RESULTS: Isolates contained macrolide resistance genes mph(A) and erm(B) and had azithromycin minimum inhibitory concentrations above the Clinical and Laboratory Standards Institute epidemiological cutoff value of ≤16 µg/mL. Among 24 patients with culture-confirmed Shigella infection, 4 were treated with azithromycin; all had clinical treatment failure and 2 also had microbiologic treatment failure. Isolates were susceptible to ciprofloxacin but contained a gyrA mutation; 2 patients failed treatment with ciprofloxacin. CONCLUSIONS: These azithromycin treatment failures demonstrate the importance of clinical breakpoints to aid clinicians in identifying alternative treatment options for resistant strains. Additionally, these treatment failures highlight a need for comprehensive susceptibility testing and systematic outcome studies, particularly given the emergence of multidrug-resistant Shigella among an expanding range of patient populations.

Disparities in Incidence and Severity of Shigella Infections Among Children-Foodborne Diseases Active Surveillance Network (FoodNet), 2009-2018.

BACKGROUND: Shigella infections are an important cause of diarrhea in young children and can result in severe complications. Disparities in Shigella infections are well documented among US adults. Our objective was to characterize disparities in incidence and severity of Shigella infections among US children. METHODS: We analyzed laboratory-diagnosed Shigella infections reported to FoodNet, an active, population-based surveillance system in 10 US sites, among children during 2009-2018. We calculated the incidence rate stratified by sex, age, race/ethnicity, Shigella species, and disease severity. Criteria for severe classification were hospitalization, bacteremia, or death. The odds of severe infection were calculated using logistic regression. RESULTS: During 2009-2018, 10 537 Shigella infections were reported in children and 1472 (14.0%) were severe. The incidence rate was 9.5 infections per 100 000 child-years and the incidence rate of severe infections was 1.3 per 100 000 child-years. Incidence was highest among children aged 1-4 years (19.5) and lowest among children aged 13-17 years (2.3); however, children aged 13-17 years had the greatest proportion of severe infections (21.2%). Incidence was highest among Black (16.2 total; 2.3 severe), Hispanic (13.1 total; 2.3 severe), and American Indian/Alaska Native (15.2 total; 2.5 severe) children. Infections caused by non-sonnei species had higher odds of severity than infections caused by Shigella sonnei (adjusted odds ratio 2.58; 95% confidence interval 2.12-3.14). CONCLUSIONS: The incidence and severity of Shigella infections among US children vary by age, race/ethnicity, and Shigella species, warranting investigation of unique risk factors among pediatric subpopulations.

Nosocomial SARS-CoV-2 transmission in a neonatal unit in Botswana: chronic overcrowding meets a novel pathogen.

We describe a cluster of six SARS-CoV-2 infections occurring in a crowded neonatal unit in Botswana, including presumed transmission among mothers, postnatal mother-to-neonate transmission and three neonate-to-healthcare worker transmissions. The affected neonate, born at 25 weeks' gestation weighing 785 g, had a positive SARS-CoV-2 test at 3 weeks of age which coincided with new onset of hypoxaemia and worsening respiratory distress. Because no isolation facility could accommodate both patient and mother, they were separated for 10 days, during which time the patient was switched from breastmilk to formula. Her subsequent clinical course was marked by several weeks of supplemental oxygen, sepsis-like presentations requiring additional antibiotics and bronchopulmonary dysplasia. Despite these complications, adequate growth was achieved likely due to early initiation of nutrition. This nosocomial cluster highlights the vulnerabilities of neonates, caregivers and healthcare workers in an overcrowded environment, and underscores the importance of uninterrupted bonding and breast feeding, even during a pandemic.

Fatal SARS-CoV-2 and Mycobacterium tuberculosis coinfection in an infant: insights from Botswana.

We report a fatal case of SARS-CoV-2 and Mycobacterium tuberculosis coinfection in an infant, Botswana's first paediatric COVID-19-associated fatality. The patient, a 3-month-old HIV-unexposed boy, presented with fever and respiratory distress in the setting of failure to thrive. Both the patient and his mother tested positive for rifampin-sensitive M. tuberculosis (Xpert MTB/Rif) and SARS-CoV-2 (real time-PCR). Initially stable on supplemental oxygen and antitubercular therapy, the patient experienced precipitous clinical decline 5 days after presentation and subsequently died. Autopsy identified evidence of disseminated tuberculosis (TB) as well as histopathological findings similar to those described in recent reports of SARS-CoV-2 infections, including diffuse microthrombosis. TB remains a serious public health threat in hyperendemic regions like sub-Saharan Africa, and is often diagnosed late in infants. In addition to raising the question of additive/synergistic pathophysiology and/or immune reconstitution, this case of coinfection also highlights the importance of leveraging the COVID-19 pandemic response to strengthen efforts for TB prevention, screening and detection.

Melioidosis in a Resident of Texas with No Recent Travel History, United States.

To our knowledge, environmental isolation of Burkholderia pseudomallei, the causative agent of melioidosis, from the continental United States has not been reported. We report a case of melioidosis in a Texas resident. Genomic analysis indicated that the isolate groups with B. pseudomallei isolates from patients in the same region, suggesting possible endemicity to this region.

First Reported Human Cases of Leptospirosis in the United States Virgin Islands in the Aftermath of Hurricanes Irma and Maria, September-November 2017.

OBJECTIVE: Following Hurricanes Irma and Maria, the first case of human leptospirosis ever identified in the US Virgin Islands (USVI) was reported to the Virgin Islands Department of Health. Leptospirosis is a potentially fatal bacterial disease caused by Leptospira species found in animal urine and urine-contaminated water and soil. Outbreaks can occur following extreme weather events. METHOD: Additional cases of leptospirosis were identified in the 2.5 months post-hurricanes by reviewing emergency department (ED) records from territorial hospitals for patients demonstrating leptospirosis-consistent symptoms, testing symptomatic patients previously enrolled in the USVI arbovirus surveillance system (VIASS), and adding leptospirosis testing prospectively to VIASS. Available patient sera underwent local rapid diagnostic testing for anti-Leptospira IgM followed by confirmatory microscopic agglutination testing at the US Centers for Disease Control and Prevention. Water was collected from cisterns with epidemiologic links to confirmed cases and tested by real-time PCR (qPCR) for pathogenic Leptospira spp. RESULTS: Sixteen retrospectively identified symptomatic patients were enrolled in VIASS; 15 with available samples tested negative. Based on review of 5226 ED charts, 6 patients were further investigated; of these, 5 were tested of which 1 was positive. Prospective leptospirosis surveillance tested 57 additional patients; of these, 1 was positive. Water from 1 of 5 tested cisterns was found positive by qPCR. CONCLUSIONS: This investigation documents the first 3 cases of leptospirosis reported in the USVI and demonstrates how VIASS successfully was adapted to establish leptospirosis surveillance. Contaminated cistern water was identified as a potential source for Leptospira spp. transmission, highlighting the need for additional post-hurricane remediation and disinfection guidance.

Hurricane-Associated Mold Exposures Among Patients at Risk for Invasive Mold Infections After Hurricane Harvey - Houston, Texas, 2017.

In August 2017, Hurricane Harvey caused unprecedented flooding and devastation to the Houston metropolitan area (1). Mold exposure was a serious concern because investigations after Hurricanes Katrina and Rita (2005) had documented extensive mold growth in flood-damaged homes (2,3). Because mold exposure can cause serious illnesses known as invasive mold infections (4,5), and immunosuppressed persons are at high risk for these infections (6,7), several federal agencies recommend that immunosuppressed persons avoid mold-contaminated sites (8,9). To assess the extent of exposure to mold and flood-damaged areas among persons at high risk for invasive mold infections after Hurricane Harvey, CDC and Texas health officials conducted a survey among 103 immunosuppressed residents in Houston. Approximately half of the participants (50) engaged in cleanup of mold and water-damaged areas; these activities included heavy cleanup (23), such as removing furniture or removing drywall, or light cleanup (27), such as wiping down walls or retrieving personal items. Among immunosuppressed persons who performed heavy cleanup, 43% reported wearing a respirator, as did 8% who performed light cleanup. One participant reported wearing all personal protective equipment (PPE) recommended for otherwise healthy persons (i.e., respirator, boots, goggles, and gloves). Immunosuppressed residents who are at high risk for invasive mold infections were exposed to mold and flood-damaged areas after Hurricane Harvey; recommendations from health care providers to avoid exposure to mold and flood-damaged areas could mitigate the risk to immunosuppressed persons.

International travel is a risk factor for extended-spectrum ß-lactamase-producing Enterobacteriaceae acquisition in children: A case-case-control study in an urban U.S. hospital.

BACKGROUND: Extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL) infections are increasing in both adults and children. The aim of this study was to describe the epidemiology of children with ESBL in an ethnically-diverse population, to determine what proportion of these infections were community-onset, and to identify risk factors predisposing children to ESBL acquisition. METHODS: A case-case-control study of children aged 0-18 years was conducted from 2012 to 2014. Patients with ESBL (detected via VITEK2) were matched 1:1:5 (based on age, sex, specimen source, and healthcare setting) with non-ESBL and uninfected controls. Data on prior antibiotic and healthcare exposure, international travel, prior urinary tract infection (UTI), comorbid gastrointestinal (GI), genitourinary (GU), neurologic, and immunocompromising conditions were collected and compared. RESULTS: Seventy-six patients were identified with 85 ESBL infections, of which 77 (91%) were E. coli. ESBL was isolated most frequently from urine (n = 72, 85%). Most infections were community-onset (n = 76, 89%) and were managed in the ambulatory setting (n = 47, 62%). On multivariate analysis, international travel (p < 0.001, OR 8.93; CI 2.92-27.78), comorbid GI condition (p = 0.002, OR 2.65, CI 1.36-5.15), Asian race (p = 0.005, OR 2.56, CI 1.34-4.89) and prior UTI (p < 0.001, OR 8.06, CI 3.47-18.87) were significant risk factors for ESBL. CONCLUSION: Most ESBL infections in this study were community-onset. To our knowledge, this is the first description of international travel as a risk factor for ESBL acquisition in children in the United States.