Positive Cerebrospinal Fluid Culture Research Articles

Successful Treatment of Carbapenem-Resistant Acinetobacter baumannii Meningitis with Sulbactam-Durlobactam.

The treatment of carbapenem-resistant Acinetobacter baumannii/calcoaceticus complex (CRAB) presents significant treatment challenges. We report the case of a 42-year-old woman with CRAB meningitis who experienced persistently positive cerebrospinal fluid (CSF) cultures for 13 days despite treatment with high-dose ampicillin-sulbactam and cefiderocol. On day 13, she was transitioned to sulbactam-durlobactam and meropenem; four subsequent CSF cultures remained negative. After 14 days of sulbactam-durlobactam, she was cured of infection. Whole genome sequencing investigations identified putative mechanisms that contributed to reduced cefiderocol susceptibility observed during cefiderocol therapy. Blood and CSF samples were collected pre-dose and 3-hours post initiation of a sulbactam-durlobactam infusion. The CRAB isolate belonged to sequence type 2. An acquired blaOXA-23 and an intrinsic blaOXA-51-like (i.e., blaOXA-66) carbapenemase gene were identified. The paradoxical effect (i.e., no growth at lower cefiderocol dilutions but growth at higher dilutions) was observed by broth microdilution after 8 days of cefiderocol exposure but not by disk diffusion. Potential markers of resistance to cefiderocol included mutations in the start codon of piuA and piuC iron transport genes and a A515V substitution in PBP3, the primary target of cefiderocol. Sulbactam and durlobactam were detected in CSF at both timepoints, indicating CSF penetration. This case describes successful treatment of refractory CRAB meningitis with the administration of sulbactam-durlobactam and meropenem and highlights the need to be cognizant of the paradoxical effect that can be observed with broth microdilution testing of CRAB isolates with cefiderocol.

Infections Associated with Medtronic Duet External Ventricular Drains - Rhode Island Hospital, Providence, Rhode Island, January 2023-January 2024.

External ventricular drains (EVDs) are medical devices that are inserted into the ventricles of the brain to drain excess fluid, manage intracranial hypertension, monitor intracranial pressure, and administer medications. Unintentional disconnections and breaks or fractures (breaks) of EVDs or associated drainage system components can result in cerebrospinal fluid (CSF) leakage and increased risk for EVD-associated infections. After replacement of Integra Life Sciences EVD systems with Medtronic Duet EVD systems at Rhode Island Hospital in mid-September 2023, a threefold increase was observed in the prevalence of positive CSF cultures, from 2.8 per 1,000 days with an EVD in place (EVD days) during January-September 2023 to 11.4 per 1,000 EVD days during October 2023-January 2024 (rate ratio [RR] = 5.7; 95% CI = 1.5-22.0; p = 0.01) and an eightfold increase in the prevalence of infections, from 0.7 to 6.5 per 1,000 EVD days (RR = 9.8; 95% CI = 1.1-87.3; p = 0.04). An investigation by Rhode Island Hospital Infection Control during December 2023-January 2024 identified frequent reports of disconnections and breaks of the Medtronic Duet EVD system. A search of the Food and Drug Administration Manufacturer and User Facility Device Experience database identified 326 reports nationwide of disconnection and breaks of components of the Duet EVD system, including 175 during 2023. A Medical Product Safety Network report was filed. The Duet EVD product was ultimately recalled in January 2024, citing disconnections of the EVD system and reports of CSF leakage and infection. Given the widespread use of EVD systems by neurosurgery centers and the risk for EVD-associated infections, a strategy for future consideration by hospital infection prevention and control programs might be inclusion of EVD-associated infections in hospital surveillance programs to rapidly identify increases in these events and determine factors related to such infections to prevent additional infections.

Targeted sequencing from cerebrospinal fluid for rapid identification of drug-resistant tuberculous meningitis.

Mortality from tuberculous meningitis (TBM) remains around 30%, with most deaths occurring within 2 months of starting treatment. Mortality from drug-resistant strains is higher still, making early detection of drug resistance (DR) essential. Targeted next-generation sequencing (tNGS) produces high read depths, allowing the detection of DR-associated alleles with low frequencies. We applied Deeplex Myc-TB-a tNGS assay-to cerebrospinal fluid (CSF) samples from 72 adults with microbiologically confirmed TBM and compared its genomic drug susceptibility predictions to a composite reference standard of phenotypic susceptibility testing (pDST) and whole genome sequencing, as well as to clinical outcomes. Deeplex detected Mycobacterium tuberculosis complex DNA in 24/72 (33.3%) CSF samples and generated full DR reports for 22/24 (91.7%). The read depth generated by Deeplex correlated with semi-quantitative results from MTB/RIF Xpert. Alleles with <20% frequency were seen at canonical loci associated with first-line DR. Disregarding these low-frequency alleles, Deeplex had 100% concordance with the composite reference standard for all drugs except pyrazinamide and streptomycin. Three patients had positive CSF cultures after 30 days of treatment; reference tests and Deeplex identified isoniazid resistance in two, and Deeplex alone identified low-frequency rifampin resistance alleles in one. Five patients died, of whom one had pDST-identified pyrazinamide resistance. tNGS on CSF can rapidly and accurately detect drug-resistant TBM, but its application is limited to those with higher bacterial loads. In those with lower bacterial burdens, alternative approaches need to be developed for both diagnosis and resistance detection.

Ventricular empyema in a dog diagnosed by magnetic resonance imaging and immediate postmortem cerebrospinal fluid culture

AbstractA 1‐year 5‐month‐old, female, neutered springer spaniel presented collapsed in extensor rigidity. The dog had undergone ovariectomy 6 weeks previously, and a tooth root abscess was documented 2 months before this. Neurological signs were first reported 24 days after surgery, starting with lethargy and tremors, which progressed to generalised tonic‐clonic cluster seizures with inter‐ictal neurological deficits by 33 days after surgery. Magnetic resonance imaging of the brain revealed a conspicuous fluid–fluid level in the lateral ventricles consistent with ventricular empyema. Treatment was declined in favour of euthanasia, but postmortem cerebrospinal fluid sample showed marked pleocytosis with elevated protein and cultured a heavy growth of Staphylococcus pseudintermedius. The magnetic resonance imaging findings and positive cerebrospinal fluid culture were consistent with bacterial meningoencephalitis. Aetiology in this case was unknown, but may have been secondary to haematogenous spread, which is a rare but potential sequel to abdominal surgery, or intracranial extension of an oral infection.

Molecular Amplification and Cell Culturing Efficiency for Enteroviruses' Detection in Cerebrospinal Fluids of Algerian Patients Suffering from Meningitis.

Enteroviruses (EVs) represent a major cause of viral meningitis, being responsible for nearly 1 billion infections each year worldwide. Several techniques were developed to obtain better diagnostic results of EV infections. Herein, we evaluated the efficiency of EV detection through isolation on both Rhabdomyosarcoma (RD) and Vero cell line cultures, conventional reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR. Thus, 50 cerebrospinal fluid (CSF) samples belonging to patients suspected to have viral meningitis in northern Algeria were collected, anonymously numbered from 1 to 50 and subjected to the above-mentioned techniques for EV detection. Using real-time RT-PCR, 34 CSF samples were revealed to be positive for viral origin of meningitis (68%). Thirteen of them were positive when the conventional RT-PCR was used (26%), and only three samples gave positive results when the cell culture technique was used (6%). Surprisingly, two cell culture-positive CSF samples, namely, 31 and 39, were negative using RT-PCR directly on the original samples. However, they turned to be positive when amplification was carried out on their corresponding cell culture supernatant. The cell-cultured viral isolates were then identified by sequencing their viral genome's VP1 regions. All of them were revealed to belong to the echovirus 27 strain. This investigation demonstrates that RT-PCR techniques are often more sensitive, accurate and much faster, providing reliable results within a clinically acceptable timeframe. However, viral isolation on cell cultures remains crucial to obtain enough viral load for serological tests or even to avoid the rare, but existing, false negative PCR.

Clinical Characteristics, Treatment, and Outcomes of Veterans with Cerebrospinal Fluid Culture Positive for Gram-Negative Rod Bacteria: A Retrospective Analysis over 18 Years in 125 Veterans Health Administration Hospitals.

Optimal management for patients with bacterial ventriculitis/meningitis due to Gram-negative rods (GNRs) has yet to be well investigated. We assessed the clinical characteristics, treatment, and outcomes of patients with a positive cerebrospinal fluid (CSF) culture for GNRs. We conducted a retrospective cohort study of all patients with a positive CSF culture within the Veterans Health Administration (VHA) system during 2003-2020. Clinical and microbiological characteristics between the true meningitis and contamination groups were compared. Of the 5919 patients with positive CSF cultures among 125 nationwide VHA acute-care hospitals, 297 (5.0%) were positive for GNRs. Among 262 patients analyzed, 156 (59.5%) were assessed as patients with true meningitis, and 106 (40.5%) were assessed as patients with contaminated CSF cultures. Patients with true meningitis had a significantly higher CSF protein (median 168 vs 57mg/dL, p < 0.001), CSF white blood cell count (median 525 vs 3/µL, p = 0.008) and percentage of neutrophils in CSF (median 88 vs 4%, p < 0.001). Enterobacterales were more common in the true meningitis group, while unidentified GNR or polymicrobial CSF cultures were more common in the contamination group. The all-cause 90-day mortality was 25.0% (39/156) in patients with true meningitis and 10.4% (11/106) in those with contaminated CSF cultures. None of the 11 patients with contaminated CSF cultures who died were considered due to missed meningitis. More than 40% of patients with a positive CSF culture with GNR did not receive treatment without negative consequences. Careful clinical judgment is required to decide whether to treat such patients.

Procalcitonin Levels in Identifying Bacterial Infections in Children with and without COVID-19.

Elevated procalcitonin levels have been associated with bacterial infection in children. Observational studies reported high procalcitonin values in COVID-19. Data on bacterial coinfections in pediatric COVID-19 is sparse; small studies suggest a low coinfection rate. In this study, we aimed to quantify the positive predictive value (PPV) of procalcitonin in identifying bacterial infection in children with and without COVID-19. A retrospective chart review was performed for 215 children <21 years admitted to our tertiary children's hospital between February 1, 2013, and July 15, 2020, who had procalcitonin levels measured within 48 hours of admission. Confirmed bacterial infection was defined as positive blood, urine, or cerebrospinal fluid (CSF) culture, positive endotracheal culture with evidence of leukocytosis on Gram stain, or pneumonia by chest radiograph. Suspected bacterial infection was defined as confirmed bacterial infection or administration of antibiotics for >48 hours. Of the 215 patients, 73 were admitted for COVID-19 (66% multisystem inflammatory syndrome in children [MIS-C], 34% acute COVID-19). The PPV of an elevated procalcitonin level >1.0 ng/mL in identifying suspected bacterial infections for those with MIS-C was 6.3% (95% CI=0-15), in acute COVID-19 was 29% (95% CI=0-62%), and in the non-COVID-19 cohort was 75% (95% CI=62-88%). For identification of confirmed bacterial infection, PPV of an elevated procalcitonin level was 0% in MIS-C, 14% (95% CI=0-40%) in acute COVID-19, and 55% (95% CI=40-69%) in the non-COVID-19 cohort. We found a low PPV of elevated procalcitonin level above 1 ng/mL in identifying either culture-confirmed or presumed bacterial infection in children hospitalized with COVID-19-related illness.

The incidence of VP shunt infection in a middle-income nation: a retrospective analysis of a pediatric population.

To investigate the incidence of infection after ventriculoperitoneal shunt (VPS) insertion at the Bustamante Hospital for Children (BHC), Jamaica, West Indies. Of the 178 patients managed by the Neurosurgery team at BHC, who underwent surgery between 2010 and 2016, 122 patients were subjected to the cerebrospinal fluid (CSF) diversion procedure through a VPS placement. The patients excluded from this study included those with a VPS placed at another institution or one placed prior to the study period. There is a notable transition that saw a switch from the use of the Codman uni-port to Medtronic shunts in 2014-2015, which initiated the process of reuse of shunt passers. Clinical data were retrospectively collected from operating theater logs and available manual health records. Over the 7-year study period of the 122 first-time shunt placements done, 17 patients (13.9%) had positive CSF cultures, with an additional six (4%) having CSF pleocytosis with negative cultures. The most common isolate was the Staphylococcus species, occurring in 60% of VPS infections. The median time to shunt infection was 2 months. Of the 72 Codman shunts placed, six became infected, and 21.7% (10 of 46) of the Medtronic shunts became infected. The rate of incidence of VPS infection was 13.9% for the period between 2010 and 2016, with most infections occurring after 2014. The major causative agent was Staphylococcus species at 60% within a median 2 months of surgery. Overall, this compares well with data reported in the literature.

Meningitis in critically ill patients admitted to intensive care unit for severe community-acquired pneumococcal pneumonia

BackgroundAlthough it has been reported that patients with pneumococcal pneumonia may develop meningitis, lumbar puncture is not systematically recommended in these patients, even in patients with associated bacteremia or invasive pneumococcal disease. The aim of this study was to determine the characteristics and outcomes of patients admitted to intensive care unit (ICU) for pneumococcal community-acquired pneumonia who developed meningitis.MethodsWe retrospectively included all consecutive patients admitted to our ICU from January 2006 to December 2020 for severe pneumococcal community-acquired pneumonia according to American Thoracic Society criteria. Meningitis was defined as pleocytosis > 5 cells/mm3 or a positive culture of cerebrospinal fluid for Streptococcus pneumoniae in lumbar puncture. The primary endpoint was the proportion of patients with meningitis during their ICU stay.ResultsOverall, 262 patients [64(52–75) years old] were included: 154(59%) were male, 80(30%) had chronic respiratory disease, 105(39%) were immunocompromised and 6(2%) were vaccinated against S. pneumoniae. A lumbar puncture was performed in 88(34%) patients with a delay from ICU admission to puncture lumbar of 10.5 (2.8–24.1) h and after the initiation of pneumococcal antibiotherapy in 81(92%) patients. Meningitis was diagnosed in 14 patients: 16% of patients with lumbar puncture and 5% of patients in the whole population. Patients with meningitis had more frequently human immunodeficiency virus positive status (29 vs. 5%, p = 0.02), neurological deficits on ICU admission (43 vs. 16%, p = 0.03) and pneumococcal bacteremia (71 vs. 30%, p < 0.01) than those without. The ICU mortality rate (14 vs. 13%, p = 0.73) and the mortality rate at Day-90 (21 vs. 15%, p = 0.83) did not differ between patients with and without meningitis. The proportion of patients with neurological disorders at ICU discharge was higher in patients with meningitis (64 vs. 23%, p < 0.001) than in those without. The other outcomes did not differ at ICU discharge, Day-30 and Day-90 between the two groups of patients.ConclusionMeningitis was diagnosed in 16% of patients with severe pneumococcal community-acquired pneumonia in whom a lumbar puncture was performed, was more frequent in patients with pneumococcal bacteremia and was associated with more frequent neurological disorders at ICU discharge. Further studies are needed to confirm these results.

Analysis of the effect of therapy for severe intracranial infection after craniotomy

ObjectiveTo retrospectively analyze the distribution characteristics of pathogenic bacteria in the cerebrospinal fluid (CSF) of patients with severe intracranial infection after craniotomy and treatment results. The aim was to provide a clinical basis and reference for improving treatment for severe intracranial infections. MethodsThis was a retrospective analysis of the distribution of pathogenic bacteria and the therapeutic effect for 43 patients who developed severe intracranial infections after craniotomy. All patients had positive CSF cultures and were treated in two hospitals in Beijing from May 2015 to May 2020. All patients received an intravenous injection of sensitive antibiotics combined with a CSF lateral ventricle catheter or lumbar cistern drainage. Antibiotic lavage treatment was administered through an external drain. ResultsThe CSF bacterial culture results for the 43 patients showed 34 single-strain infections (26 Gram-positive bacteria and 8 Gram-negative bacteria) and 9 multistrain infections. Fifty-two pathogenic strains were isolated, namely 32 Gram-positive bacteria (61.54%), 18 Gram-negative bacteria (34.61%), and 2 fungi (3.85%). After combined treatment, 29 patients (67.44%) were cured; treatment was effective for 7 patients (16.28%) and ineffective for 7 patients (16.28%). After 6 months of follow-up, the 36 surviving patients were cured of infection. The Glasgow Outcome Scale score results showed that 5 of the 36 (13.9%) patients had a persistent vegetative state; 13 (36.1%) had severe disability; 12 (33.3%) had moderate disability; and 6 (16.7%) had mild disability. ConclusionCSF pathogenic bacteria in patients with intracranial infection after craniotomy were mainly Gram-positive bacteria, primarily Staphylococcus epidermidis. A small number of patients had mixed bacterial infections. Owing to the presence of implanted devices in patients who underwent ventriculoperitoneal shunt surgery, the antibacterial therapeutic effect was worse than that for other types of postoperative infections. Therefore, when initial intravenous antibiotics are ineffective, the shunt device should be removed or replaced as soon as possible. When initial intravenous antibiotics are ineffective and severe intracranial infection occurs, a combined treatment plan should be adopted. That is, CSF drainage and antibiotic lavage should be performed cautiously with the intravenous injection of sensitive antibiotics. Our clinical data confirmed that postoperative neurosurgical infection could lead to different degrees of nerve dysfunction, which should be considered.

Prevalence and Antibiotic Resistance of Bacteria Isolated from Cerebrospinal Fluid of Neurosurgical Patients in Malang, Indonesia

Background: Central nervous system infections are a critical concern in neurosurgical practice, often leading to severe complications and prolonged hospital stays. Understanding the prevalence and antibiotic resistance patterns of the bacteria causing these infections is essential for effective patient management. This study aims to investigate the prevalence and antibiotic resistance profiles of bacteria isolated from cerebrospinal fluid in neurosurgical patients in Malang, Indonesia. Materials and Methods: A retrospective analysis was conducted to investigate the positive cerebrospinal fluid (CSF) cultures in patients who underwent craniotomy within the period of January 2019 to December 2021. The gathered data encompassed the identification of etiological agents and the determination of their respective antimicrobial susceptibilities. Data analysis was performed on a total of 33 individuals, with 67 isolates out of 239 patients and 515 CSF culture samples. Results: The preponderant microorganism identified in the sample was coagulase-negative Staphylococci, with a majority exhibiting methicillin resistance, commonly referred to as methicillin-resistant coagulase-negative Staphylococci (MRCoNS). All specimens exhibited susceptibility to both vancomycin and tigecycline. Klebsiella pneumoniae, a Gram-negative bacterium, was identified as the predominant etiological agent and exhibited resistance to a substantial proportion of the antimicrobial agents tested, specifically 13 out of the 16 antimicrobials evaluated. Conclusions: The sensitivity rates of ceftriaxone and meropenem were found to be 0% and 100%, respectively. The predominant bacteria is MRCoNS, which is completely susceptible to tigecycline, vancomycin, linezolid, and nitrofurantoin. Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae is difficult to treat, especially in central nervous system infections when antimicrobials are scarce.

Time to Positive Blood and Cerebrospinal Fluid Cultures in Hypothermic Young Infants.

Hypothermia in young infants may be secondary to an invasive bacterial infection. No studies have explored culture time-to-positivity (TTP) in hypothermic infants. Our objective was to compare TTP of blood and cerebrospinal fluid (CSF) cultures between pathogenic and contaminant bacteria in hypothermic infants ≤90 days of age. Secondary analysis of a retrospective cohort of 9 children's hospitals. Infants ≤90 days of age presenting to the emergency department or inpatient setting with hypothermia from September 1, 2017, to May 5, 2021, with positive blood or CSF cultures were included. Differences in continuous variables between pathogenic and contaminant organism groups were tested using a 2-sample t test and 95% confidence intervals for the mean differences reported. Seventy-seven infants met inclusion criteria. Seventy-one blood cultures were positive, with 20 (28.2%) treated as pathogenic organisms. Five (50%) of 10 positive CSF cultures were treated as pathogenic. The median (interquartile range [IQR]) TTP for pathogenic blood cultures was 16.8 (IQR 12.7-19.2) hours compared with 26.11 (IQR 20.5-48.1) hours for contaminant organisms (P < .001). The median TTP for pathogenic organisms on CSF cultures was 34.3 (IQR 2.0-53.7) hours, compared with 58.1 (IQR 52-72) hours for contaminant CSF organisms (P < .186). Our study is the first to compare the TTP of blood and CSF cultures between pathogenic and contaminant bacteria in hypothermic infants. All pathogenic bacteria in the blood grew within 36 hours. No difference in TTP of CSF cultures between pathogenic and contaminant bacteria was detected.

2438. Positive Cerebrospinal Fluid Cultures from Intraventricular Reservoirs for CLN2 Patients: One Institution's Experience

Abstract Background Enzyme replacement therapy (ERT) with cerliponase alfa (Brineura) has been shown to slow progression of milestone deterioration in Neuronal Ceroid Lipofuscinosis Type 2 (CLN2), an inherited neurodegenerative lysosomal storage disorder. Brineura must be administered intraventricularly every 2 weeks, necessitating the placement of ventricular reservoirs and requiring frequent access. Traditionally, positive cerebrospinal fluid (CSF) cultures are managed with device replacement and antibiotic treatment. We sought to establish which circumstances might allow for careful observation without device removal. In this study, we report our single-institution experience with clinical outcomes of positive CSF cultures in 16 CLN2 patients over 6 years. Methods We retrospectively reviewed a cohort of 16 patients with CLN2 disease who had ventricular reservoirs placed for ERT administration. At each ERT infusion, CSF was collected by sterile technique and cultured by both thioglycolate broth and agar plate. Epidemiologic and microbiologic data, symptomatology, total antibiotic days, removal and replacement of ventricular reservoir, hospital length of stay, and mortality were analyzed for each patient. Results In our cohort, 11 of 16 patients (69%) had at least one positive CSF culture (Fig 1). Of the 11 with positive cultures, only 3 had their device removed and replaced for a positive culture with concurrent antibiotic treatment at our center, and 2 patients subsequently have been treated with prophylactic antibiotics at infusions (Fig 2). Out of 1401 total CSF cultures, 64 (4.56%) were positive. The most common organism grown was Cutibacterium acnes, which typically grew in only broth culture (82%), suggesting low bacterial burden (Fig 3). The other 7 patients with positive cultures remained asymptomatic with no intervention required. Conclusion At our institution, we have found that in asymptomatic patients with frequently accessed ventricular reservoirs, positive CSF culture with low virulence skin flora was common, and rarely required intervention. This strategy reduced the risks of invasive surgery, prolonged antibiotic courses, and missed infusions. In the future, routine screening cultures in asymptomatic patients can be avoided. Disclosures Raymond Wang, MD, Biomarin Pharmaceutical: Advisor/Consultant|Biomarin Pharmaceutical: Grant/Research Support|Biomarin Pharmaceutical: equity interest Antonio C. Arrieta, MD, FIDSA, FPIDS, Astellas Pharma Global Development, Inc.: Advisor/Consultant|Astellas Pharma Global Development, Inc.: Grant/Research Support|Astellas Pharma Global Development, Inc.: Honoraria|Cumberland Pharmaceutical: Grant/Research Support|IDbyDNA: Advisor/Consultant|IDbyDNA: Grant/Research Support|Melinta: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Nabriva: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support|Pfizer, Inc: Advisor/Consultant|Pfizer, Inc: Grant/Research Support|Roche/Genentech: Grant/Research Support|The Medicine Company: Grant/Research Support

World Health Organization Danger Signs to predict bacterial sepsis in young infants: A pragmatic cohort study.

Bacterial sepsis is generally a major concern in ill infants. To help triaging decisions by front-line health workers in these situations, the World Health Organization (WHO) has developed danger signs (DS). The objective of this study was to evaluate the extent to which nine DS predict bacterial sepsis in young infants presenting with suspected sepsis in a low-income country setting. The study pragmatically evaluated nine DS in infants younger than 3 months with suspected sepsis in a regional hospital in Lilongwe, Malawi, between June 2018 and April 2020. Main outcomes were positive blood or cerebrospinal fluid (CSF) cultures for neonatal pathogens, and mortality. Among 401 infants (gestational age [mean ± SD]: 37.1±3.3 weeks, birth weight 2865±785 grams), 41 had positive blood or CSF cultures for a neonatal pathogen. In-hospital mortality occurred in 9.7% of infants overall (N = 39/401), of which 61.5% (24/39) occurred within 48 hours of admission. Mortality was higher in infants with bacterial sepsis compared to other infants (22.0% [9/41] versus 8.3% [30/360]; p = 0.005). All DS were associated with mortality except for temperature instability and tachypnea, whereas none of the DS were significantly associated with bacterial sepsis, except for "unable to feed" (OR 2.25; 95%CI: 1.17-4.44; p = 0.017). The number of DS predicted mortality (OR: 1.75; 95%CI: 1.43-2.17; p<0.001; AUC: 0.756), but was marginally associated with positive cultures with a neonatal pathogen (OR 1.22; 95%CI: 1.00-1.49; p = 0.046; AUC: 0.743). The association between number of DS and mortality remained significant after adjusting for admission weight, the only statistically significant co-variable (OR 1.75 [95% CI: 1.39-2.23]; p<0.001). Considering all positive cultures including potential bacterial contaminants resulted a non-significant association between number of DS and sepsis (OR 1.09 [95% CI: 0.93-1.28]; p = 0.273). In conclusion, this study shows that DS were strongly associated with death, but were marginally associated with culture-positive pathogen sepsis in a regional hospital setting. These data imply that the incidence of bacterial sepsis and attributable mortality in infants in LMIC settings may be inaccurately estimated based on clinical signs alone.

Antibiotic Therapy for Pneumonia in the Neonatal Intensive Care Unit: Is 5 Days Enough?

Abstract Background Antibiotic therapy provided to infants in the NICU is associated with both short-and-long-term adverse consequences. In 2019, the Neonatal Antimicrobial Stewardship Program (NEO-ASP) at Nationwide Children’s Hospital (NCH), Columbus, OH, recommended a five-day antibiotic course with a time-out for treatment of pneumonia in the seven NCH network NICUs. Objective To determine the duration of antibiotic therapy for pneumonia after implementation of a 5-day antibiotic treatment course and describe its safety among infants in the NICU. Methods Prospective surveillance of antibiotic therapy provided to infants in 7 NCH NICUs (1, level 4; 5, Level 3; 1, level 2) who were diagnosed with pneumonia by the attending neonatologist based on clinical and radiographic abnormalities from 8/2020 to 4/2022. Pertinent clinical, laboratory, and microbiologic data were obtained from electronic health records. Infants were excluded if they had positive bacterial cultures of blood, urine, or cerebrospinal fluid. The length of therapy (LOT) was defined as any calendar day that the infant received ≥1 antibiotic while definitive treatment course was the duration of appropriate antibiotic therapy. Safety was defined a priori by re-initiation of antibiotic therapy within 14 days after discontinuation of the initial treatment and/or mortality (overall/sepsis-related). Results From 8/2020 to 4/2022, NICU infants (66% male) were diagnosed with 136 episodes of pneumonia at a median (IQR) age of 2 (1-20) days. 61 (45%) of episodes were late onset at ≥3 days of age. All infants had sterile cultures of blood, urine, and cerebrospinal fluid, if performed. Their median (IQR) birth weight and gestational age were 2780 (1090-3450) g and 36 (28-38) wk, respectively. At the time of pneumonia diagnosis, 44% of infants were receiving CPAP while 55% were on mechanical ventilation (11% high frequency oscillatory ventilation). The median (IQR) LOT was 6 (5-6) days and length of definitive treatment was 5 (5-5) days. Overall mortality was 5% (7/128) with 2% of deaths being sepsis-related (n=3; Table 1). The majority of pneumonia episodes (88%; n=120) were treated with 5 days of definitive antibiotic therapy and 22 (16%) episodes had antibiotics restarted within 14 days (Table 1). There was no significant difference in the composite safety outcome between ≤5 vs. 6-20 days of definitive antibiotic therapy (p=0.29). Table 1. Safety assessments of definitive antibiotic treatment for 136 pneumonia episodes in 128 infants Table 2. Underlying conditions, antibiotic duration, and cause of death among 7 infants in the NICU Conclusion(s) There was excellent adherence (88%) to the NEO-ASP recommendation of a 5-day definitive treatment course for pneumonia and in addition, the intervention seemed safe.

The Prognostic Nutritional Index and Mortality in Patients With Ventriculoperitoneal Shunt Infection

The objective of this study was to investigate the relationship between mortality and the prognostic nutritional index (PNI) in the pediatric patient group with ventriculoperitoneal shunt (VPS) infection. A total of 63 pediatric patients with a VPS infection and positive cerebrospinal fluid (CSF) culture were retrospectively registered. The CSF specimens were analyzed to conduct culture and microscopic evaluation. A total of 44.4% of the cases were men and 55.6% of the cases were women. Patients were divided into 2 groups (survivor and non-survivor patients). When survivor and non-survivor patients were compared, it was found that CSF leukocytes, CSF glucose, CSF protein, CSF/blood glucose ratio, lymphocyte, albumin, and PNI levels were lower in the non-survivor patients’ group. Nevertheless, blood glucose and CRP (C-reactive protein) were significantly higher in the non-survivor patients’ group than in the survivor patients’ group. In our investigation, we suggested that low PNI was related to high mortality in cases of VPS infection.

Comparison of the level of vitamin D in preterm infected and uninfected infants

Introduction. Despite the substantial progress in intensive cares, sepsis is still an important cause of neonatal mortality. Given the role of vitamin D in infection control, this study was conducted to compare vitamin D level in infected and uninfected preterm infants. Materials and methods. This cross-sectional study was carried out on 87 preterm infants (45 infected infants and 42 uninfected infants) hospitalized in Mashhad Ghaem Hospital, Iran, during 20152017. The subjects were selected by using convenience sampling. The infected infants (n = 45) included babies with clinical and laboratory findings compatible with infection and/or positive blood or cerebrospinal fluid cultures. The serum levels vitamin D were measured in all infants. A researcher-made questionnaire containing demographic, clinical and laboratory features of infants was used. In addition, independent t-test and chi-square test were applied. SPSS was used to perform the statistical data analysis. Results. 83% of infants had vitamin D deficiency 34.5%, 26.4%, and 21.8% of whom exhibited severe (less than 10 ng/ml), moderate (10.120 ng/ml), mild deficiency (20.130 ng/ml), respectively. The mean vitamin D level of infants was 23.319.40 ng/ml in the control group and 11.028.64 ng/ml in the case group (p = 0.000). In the case group, the mean vitamin D was 8.145.53 ng/ml in early sepsis and 12.629.75 ng/ml in late-onset sepsis (p = 0.121). 95% of infected infants and 71% of uninfected infants had vitamin D less than 30 ng/ml (p = 0.003). Conclusion. Vitamin D deficiency is very common in preterm infants. Serum vitamin D levels in infants with sepsis were lower than those in uninfected infants. Therefore, the correction of vitamin D deficiency may contribute to better control of neonatal infection.

Prevalence of Invasive Bacterial Infection in Hypothermic Young Infants: A Multisite Study

To determine the prevalence of bacteremia and meningitis (invasive bacterial infection [IBI]) in hypothermic young infants, and also to determine the prevalence of serious bacterial infections (SBI) and neonatal herpes simplex virus and to identify characteristics associated with IBI. We conducted a retrospective cohort study of infants ≤90days of age who presented to 1 of 9 hospitals with historical or documented hypothermia (temperature ≤36.0°C) from September 1, 2017, to May 5, 2021. Infants were identified by billing codes or electronic medical record search of hypothermic temperatures. All charts were manually reviewed. Infants with hypothermia during birth hospitalization, and febrile infants were excluded. IBI was defined as positive blood culture and/or cerebrospinal fluid culture treated as a pathogenic organism, whereas SBI also included urinary tract infection. We used multivariable mixed-effects logistic regression to identify associations between exposure variables and IBI. Overall, 1098 young infants met the inclusion criteria. IBI prevalence was 2.1% (95% CI, 1.3-2.9) (bacteremia 1.8%; bacterial meningitis 0.5%). SBI prevalence was 4.4% (95% CI, 3.2-5.6), and neonatal herpes simplex virus prevalence was 1.3% (95% CI, 0.6-1.9). Significant associations were found between IBI and repeated temperature instability (OR, 4.9; 95% CI, 1.3-18.1), white blood cell count abnormalities (OR, 4.8; 95% CI, 1.8-13.1), and thrombocytopenia (OR, 5.0; 95% CI, 1.4-17.0). IBI prevalence in hypothermic young infants is 2.1%. Further understanding of characteristics associated with IBI can guide the development decision tools for management of hypothermic young infants.

Failure of Early Mycological Clearance in HIV-Negative Cryptococcal Meningitis.

Negative cerebrospinal fluid (CSF) cultures at 2 weeks after antifungal treatment (early mycological clearance [EMC]) should be a treatment goal of cryptococcal meningitis (CM). However, EMC in human immunodeficiency virus (HIV)-negative patients with CM is poorly understood. We conducted a retrospective review of medical records and 1-year follow-up of 141 HIV-negative patients with CM with an initial positive CSF culture for Cryptococcus neoformans. Multivariate logistic regression was performed to analyze clinical features and laboratory and CSF findings of patients with CM with different EMC statuses. Random forest models were used to predict failure of EMC. All-cause mortality and clinical functional status were analyzed. Of 141 patients, 28 (19.9%) had EMC failure. The 1-year mortality rate was 5.7% (8/141). Multivariate analysis showed that non-amphotericin B (AmB)-based regimens, baseline log10 Cryptococcus count/mL, baseline CSF opening pressure (CSF-OP) >30 cm H2O, and baseline serum creatinine were significantly associated with EMC failure. A parsimonious predictive rule given by the decision tree identified patients with CM with non-AmB-based therapy and baseline CSF-OP >30 cm H2O as being at high risk of EMC failure. Incidence of all-cause mortality, the follow-up modified Rankin Scale, and Karnofsky performance status scores were not significantly related to EMC. EMC failure in HIV-negative CM is attributed to non-AmB-based therapy and is associated with log10 Cryptococcus count/mL and CSF-OP >30 cm H2O at baseline. Because of the small number of deaths, we are not able to comment on whether or not EMC is associated with mortality.

Short-course empiric antibiotic therapy for possible early-onset sepsis in the NICU.

On 2/2019, the Neonatal Antimicrobial Stewardship Program at Nationwide Children's Hospital recommended reducing empirical antibiotic therapy for early-onset sepsis (EOS) from 48 to 24 hours with a TIME-OUT. We describe our experience with this guideline and assess its safety. Retrospective review of newborns evaluated for possible EOS at 6 NICUs from 12/2018-7/2019. Safety endpoints were re-initiation of antibiotics within 7 days after discontinuation of the initial course, positive bacterial blood or cerebrospinal fluid culture in the 7 days after antibiotic discontinuation, and overall and sepsis-related mortality. Among 414 newborns evaluated for EOS, 196 (47%) received a 24 hour rule-out sepsis antibiotic course while 218 (53%) were managed with a 48 hour course. The 24-hour rule-out group were less likely to have antibiotics re-initiated and did not differ in the other predefined safety endpoints. Antibiotic therapy for suspected EOS may be discontinued safely within 24 hours.