The identification of risk factors and outcomes of cerebrospinal fluid shunt infections caused by carbapenem-resistant gram-negative bacteria in children: a retrospective cohort.

OBJECTIVE: Cerebrospinal fluid (CSF) shunt infections caused by gram-negative bacteria are difficult to treat given the limited treatment options and the emergence of carbapenem-resistant (CR) strains. This study aimed to evaluate the demographic and clinical characteristics of children with CSF shunt and external ventricular drain (EVD) infections caused by gram-negative bacteria, to identify the risk factors for acquiring CR CSF shunt infections, and to report on the clinical outcomes of these infections. METHODS: A retrospective cohort study was designed to evaluate pediatric patients with CSF shunt and EVD infections caused by gram-negative bacteria between January 2013 and February 2023. RESULTS: A total of 64 episodes in 50 patients were evaluated. There were 45 (70.3%) CSF shunt infections and 19 (29.7%) EVD infections. The median (range) ages were 1.4 years (9 months-17.5 years) for CSF shunt infection patients and 4.2 years (1 month-17 years) for EVD infection patients. The most common isolated gram-negative bacteria species in CSF shunt infections were Pseudomonas spp. (12, 26.7%), followed by Escherichia coli (11, 24.4%), Klebsiella pneumoniae (9, 20%), and Enterobacter cloacae (5, 11.1%). In EVD infections, the most common isolated gram-negative bacteria species were Acinetobacter spp. (6, 31.6%), followed by Pseudomonas spp. (4, 21.1%) and E. coli (3, 15.8%). The carbapenem resistance rate was 26.3% (n = 5) in EVD infections and 26.2% (n = 11) in CSF shunt infections. When risk factors for carbapenem resistance were evaluated for CSF shunt infections, prior carbapenem treatment and a prolonged hospital stay > 7 days were risk factors for the CR group (p = 0.032 and p = 0.042, respectively). In definitive treatment, colistin was statistically more commonly used in the CR group (p = 0.049). When outcomes were evaluated, the 30-day mortality rate (18.2% vs 0%) was higher in the CR group, without a significant difference (p = 0.064). CONCLUSIONS: A prolonged hospital stay > 7 days and prior carbapenem exposure within 30 days were associated with CR shunt infections caused by gram-negative bacteria.

When a Root Is the Cause of Infection.

BACKGROUND: Sinorhizobium meliloti is a phytobacterium found in the root nodules of plants, where it is involved in fixing nitrogen for delivery to the roots in exchange for a photosynthate carbon source. There have been no reported cases of S. meliloti infection in humans. We conducted a retrospective review of clinical records and diagnostic tests. CASE DESCRIPTION: An 81-year-old woman who presented to the emergency department with a 1-day history of progressive decline in her level of consciousness following a head injury and deep scalp laceration. Her medical history was significant for a ventriculoperitoneal shunt due to normal pressure hydrocephalus. Imaging studies revealed hydrocephalus and a tear in the shunt catheter. Cerebrospinal fluid analysis was not suggestive for meningitis. Cerebrospinal fluid culture revealed an unfamiliar organism, identified as S. meliloti following sequencing of its entire genome, which was considered a contaminant. The patient subsequently developed peritonitis, and the same pathogen was detected in the peritoneal fluid, suggesting distal shunt infection. Symptoms resolved after shunt removal and antibiotic treatment. Thorough history taking revealed that the patient had fallen and struck her head against a flowerpot. CONCLUSIONS: S. meliloti is a phytopathogen that should not be easily disregarded as a contaminant when isolated from human sterile fluids or tissues. Aggressive management including removal of infected hardware, if present, is required to ensure resolution of infection. It emphasizes the importance of thorough history taking.

A Seven-year Study on the Effects of Intravenous Antibiotic Therapy on Infection of Ventriculoperitoneal Shunts in Children.

BACKGROUND: Infection is one of the most common complications of ventriculoperitoneal (VP) shunts. Its optimal management is controversial. We aimed to report current practice within a large pediatric neurosurgical center. METHODS: We retrospectively studied a cohort of children <15 years with VP shunt infection, who underwent treatment from March 2011 to March 2018 in the main referral children hospital in Isfahan, Iran. Patients with distal shunt infection or associated wound infection were not included. The initial protocol was empiric intravenous antibiotic therapy and repeated evaluation of cerebrospinal fluid (CSF) analysis and culture. After obtaining the culture results, antibiotic regimen was adjusted according to the sensitivity results. Response to protocol was defined as negative culture results after 72 hours of appropriate antibiotic, which persisted at least for 1 month after discontinuation of therapy. In patients who failed to respond to protocol, the shunts were replaced. RESULTS: Totally, 148 cases with mean (SD) age of 21.2 (30.1) months included to the study. Of which, 56.1% were boys and 68.2% had responded to the protocol. This response was significantly prominent in patients who infected with Gram-negative bacteria (82.9%), especially with Acinetobacter spp. (100%) and Pseudomonas aeruginosa (100%). The response was significantly higher in patients with CSF glucose of greater than 40 mg/dl (83% versus 58.1%, respectively, P = 0.004). CONCLUSION: We found that using only intravenous antibiotics is sufficiently enough for treating many children with VP shunt infections, especially in those infected by Gram-negative organisms and CSF glucose level of greater than 40 mg/dl.

The Causative Organisms of Bacterial Meningitis and their Antimicrobial Resistance Profiles in Iranian Children in 2011-2016.

OBJECTIVES: The study aimed to describe the identity and antimicrobial resistance patterns of the causative agents of bacterial meningitis in children referred to Children's Medical Center (CMC) Hospital, Tehran, Iran. METHODS: This retrospective study was performed at CMC Hospital during a six-year period from 2011 to 2016. The microbiological information of the patients with a diagnosis of bacterial meningitis was collected and the following data were obtained: patients' age, sex, hospital ward, the results of CSF and blood cultures, and antibiotic susceptibility profiles of isolated organisms. RESULTS: A total of 118 patients with bacterial meningitis were admitted to CMC hospital. Sixty-two percent (n=73) of the patients were male. The median age of the patients was ten months (interquartile range [IQR]: 2 months-2 years) and the majority of them (n=92, 80%) were younger than two years of age. The highest number of patients (n=47, 40%) were admitted to the surgery department. Streptococcus epidermidis was the most frequent isolated bacterium (n=27/127, 21%), followed by Klebsiella pneumoniae (n=20/127, 16%), and Staphylococcus aureus (n=16/127, 12.5%). Blood culture was positive in 28% (n=33/118) of patients. Ampicillin-sulbactam and imipenem were the most effective antibiotics against Gram-negative bacteria isolated from CSF cultures. In the case of Gram-positive organisms, ampicillinsulbactam, vancomycin, and linezolid were the best choices. Imipenem was the most active drug against Gram-negative blood pathogens. Also, ampicillin and vancomycin had the best effect on Gram-positive bacteria isolated from blood cultures. CONCLUSION: Results of this study provide valuable information about the antibiotic resistance profiles of the etiologic agents of childhood meningitis, which can be used for prescription of more effective empirical therapies.

Risk factors for surgical site infection after craniotomy: a prospective cohort study.

Background: Although surgical site infection after craniotomy (SSI-CRAN) is a serious complication, risk factors for its development have not been well defined. We aim to identify the risk factors for developing SSI-CRAN in a large prospective cohort of adult patients undergoing craniotomy. Methods: A series of consecutive patients who underwent craniotomy at a university hospital from January 2013 to December 2015 were prospectively assessed. Demographic, epidemiological, surgical, clinical and microbiological data were collected. Patients were followed up in an active post-discharge surveillance programm e for up to one year after surgery. Multivariate analysis was carried out to identify independent risk factors for SSI-CRAN. Results: Among the 595 patients who underwent craniotomy, 91 (15.3%) episodes of SSI-CRAN were recorded, 67 (73.6%) of which were organ/space. Baseline demographic characteristics were similar among patients who developed SSI-CRAN and those who did not. The most frequent causative Gram-positive organisms were Cutibacterium acnes (23.1%) and Staphylococcus epidermidis (23.1%), whereas Enterobacter cloacae (12.1%) was the most commonly isolated Gram-negative agent. In the univariate analysis the factors associated with SSI-CRAN were ASA score > 2 (48.4% vs. 35.5% in SSI-CRAN and no SSI-CRAN respectively, p = 0.025), extrinsic tumour (28.6% vs. 19.2%, p = 0.05), and re-intervention (4.4% vs. 1.4%, p = < 0.001). In the multivariate analysis, ASA score > 2 (AOR: 2.26, 95% CI: 1.32-3.87; p = .003) and re-intervention (OR: 8.93, 95% CI: 5.33-14.96; p < 0.001) were the only factors independently associated with SSI-CRAN. Conclusion: The risk factors and causative agents of SSI-CRAN identified in this study should be considered in the design of preventive strategies aimed to reduce the incidence of this serious complication.

CSF inflammatory markers differ in gram-positive versus gram-negative shunt infections.

BACKGROUND: Cerebrospinal fluid (CSF) shunt placement is frequently complicated by bacterial infection. Shunt infection diagnosis relies on bacterial culture of CSF which can often produce false-negative results. Negative cultures present a conundrum for physicians as they are left to rely on other CSF indices, which can be unremarkable. New methods are needed to swiftly and accurately diagnose shunt infections. CSF chemokines and cytokines may prove useful as diagnostic biomarkers. The objective of this study was to evaluate the potential of systemic and CSF biomarkers for identification of CSF shunt infection. METHODS: We conducted a retrospective chart review of children with culture-confirmed CSF shunt infection at Children's Hospital and Medical Center from July 2013 to December 2015. CSF cytokine analysis was performed for those patients with CSF in frozen storage from the same sample that was used for diagnostic culture. RESULTS: A total of 12 infections were included in this study. Patients with shunt infection had a median C-reactive protein (CRP) of 18.25 mg/dL. Median peripheral white blood cell count was 15.53 × 103 cells/mL. Those with shunt infection had a median CSF WBC of 332 cells/mL, median CSF protein level of 406 mg/dL, and median CSF glucose of 35.5 mg/dL. An interesting trend was observed with gram-positive infections having higher levels of the anti-inflammatory cytokine interleukin (IL)-10 as well as IL-17A and vascular endothelial growth factor (VEGF) compared to gram-negative infections, although these differences did not reach statistical significance. Conversely, gram-negative infections displayed higher levels of the pro-inflammatory cytokines IL-1ß, fractalkine (CX3CL1), chemokine ligand 2 (CCL2), and chemokine ligand 3 (CCL3), although again these were not significantly different. CSF from gram-positive and gram-negative shunt infections had similar levels of interferon gamma (INF-γ), tumor necrosis factor alpha (TNF-α), IL-6, and IL-8. CONCLUSIONS: This pilot study is the first to characterize the CSF cytokine profile in patients with CSF shunt infection and supports the distinction of chemokine and cytokine profiles between gram-negative and gram-positive infections. Additionally, it demonstrates the potential of CSF chemokines and cytokines as biomarkers for the diagnosis of shunt infection.

Impact of Ceftazidime Use on Susceptibility Patterns in the Neonatal Intensive Care Unit.

BACKGROUND: Ceftazidime use in the neonatal intensive care unit (NICU) has increased after a cefotaxime shortage. The impact of this change is unknown. The purpose was to assess the effect of increased ceftazidime use on susceptibilities of Gram-negative organisms in the NICU. METHODS: Retrospective study of Gram-negative isolates identified in blood, urine, cerebrospinal fluid, tracheostomy, abdominal fluid and pleural fluid cultures from a single-center NICU over a 5-year period. Duplicate cultures that occurred within 90 days were noted. Pre- and postshortage periods were defined based on cessation of cefotaxime. Third- and fourth-generation cephalosporin susceptibility rates were compared between periods, as well as rates of extended-spectrum beta-lactamase (ESBL) Escherichia coli and Klebsiella species. RESULTS: Analysis included 666 isolates. Twelve (1.8%) were duplicate isolates that occurred after a 90-day period. The preshortage period included 464 (69.7%) isolates, and the postshortage included 202 (30.3%). No significant differences in susceptibility rates were noted when excluding duplicates. No difference in ESBL rates for E. coli were noted between periods (3.8% vs. 4.9%, P =1.000). No ESBL-positive Klebsiella species were identified. A post-hoc analysis of duplicate isolates demonstrated significant lower susceptibility rates for Pseudomonas aeruginosa to ceftazidime (risk ratio 0.58; 95% CI: 0.43-0.79) and cefepime (risk ratio 0.66; 95% CI: 0.51-0.86). CONCLUSIONS: Ceftazidime use did not appear to affect susceptibility rates for third- and fourth-generation cephalosporins for most Gram-negative organisms in the short-term of 1.5 years. However, susceptibility rates for P. aeruginosa decreased when evaluating duplicate isolates. Long-term monitoring is needed to assess the true impact.

Diagnosis and treatment of severe neurosurgical patients with pyogenic ventriculitis caused by gram-negative bacteria.

The aim of the study is to explore the experiences in diagnosis and treatment of severe neurosurgical patients with pyogenic ventriculitis caused by gram-negative bacteria (G-). Nineteen patients with pyogenic ventriculitis were reviewed for their treatment. The bacterial testing results of cerebrospinal fluid (CSF), the clinical intervention, and the patients' prognosis were evaluated. The bacterial smears of ventricular drainage from all the cases were G- bacteria. Head CT and MRI scans confirmed that they were intraventricular empyema. Eighteen cases of CSF bacterial test were positive, including 12 cases of Acinetobacter baumannii positive, 2 of Klebsiella pneumonia positive, 2 of Serratia marcescens positive, 1 of Pseudomonas maltophila positive, and 1 case of Escherichia coli positive. One case of the bacterial culture was negative. All patients were treated by using intraventricular lavage in combination with intravenous and intraventricular antibiotics in accordance with the clinical conditions. After treatment for 2 to 8 weeks, 14 patients were cured (74%) and 5 were died (26%). Eight patients who were cured had received ventriculoperitoneal shunt due to hydrocephalus at 2 to 6 weeks after infection controlled, and none of them had any reinfection. Twelve of the 14 cured cases came to consciousness, but 2 were persistent in vegetative state starting before the infection; they did not show any improving consciousness after infection had been cured. Suppurative ventriculitis in severe neurosurgical patients is mainly infected by G- with a higher mortality. Early diagnosis, especially in identifying pathogen types, timely ventricular irrigation, and ventricular drainage together with intravenous and intraventricular antibiotic treatment, should improve prognosis.

Clinical and Microbiologic Characteristics of Early-onset Sepsis Among Very Low Birth Weight Infants: Opportunities for Antibiotic Stewardship.

BACKGROUND: Most very low birth weight (VLBW, birth weight <1500 g) infants receive empiric antibiotics for risk of early-onset sepsis (EOS). The objective of this study was to determine the characteristics of VLBW infants with culture-confirmed EOS at a single center during 25 years and to identify opportunities for antibiotic stewardship. METHODS: Retrospective cohort study includes VLBW infants admitted from 1990 to 2015. EOS was defined as isolation of a pathogen in blood or cerebrospinal fluid culture obtained at <72 hours of age. Clinical and microbiologic characteristics of EOS case infants were obtained by review of medical, laboratory and administrative records. Blood culture, antibiotic initiation and maternal discharge code data were available for all VLBW infants born between 1999 and 2013. RESULT: One-hundred nine EOS cases (20.5/1000 VLBW births) occurred during the study period. Preterm labor, preterm rupture of membranes and/or the obstetrical diagnosis of chorioamnionitis were present in 106/109 cases (97%). Obligate anaerobic organisms accounted for 16% of cases. Time to culture positivity was 36 hours for 88% and 48 hours for 98% of cases. From 1999 to 2013, 97% of VLBW infants were evaluated for EOS and 90% administered empiric antibiotics; 22% of these infants were born by cesarean section to mothers with preeclampsia and without preterm labor or chorioamnionitis and had a 12-fold lower incidence of EOS compared with the remaining infants. CONCLUSION: Decisions to initiate and discontinue empiric antibiotics among VLBW infants can be informed by the delivery characteristics of infected infants and by local microbiologic data.

Comparative study of bacteriological culture and real-time fluorescence quantitative PCR (RT-PCR) and multiplex PCR-based reverse line blot (mPCR/RLB) hybridization assay in the diagnosis of bacterial neonatal meningitis.

BACKGROUND: Bacterial meningitis is more common in the neonatal period than any other time in life; however, it is still a challenge for the evidence based diagnosis. Strategy for identification of neonatal bacterial meningitis pathogens is presented by evaluating three different available methods to establish evidence-based diagnosis for neonatal bacterial meningitis. METHODS: The cerebrospinal fluid samples from 56 neonates diagnosed as bacterial meningitis in 2009 in Beijing Children's Hospital were analyzed in the study. Two PCR based molecular assays, real-time fluorescence quantitative PCR (RT-PCR) and multiplex PCR based-reverse line blot hybridization (mPCR/RLB), were used to assess 7 common neonatal meningitis bacterial pathongens, including Escherichia coli, Staphylococcus aureus, Listerisa monocytogenes, Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus agalactiae. The findings in examinations of two assays were compared with the results obtained bacterial culture tests. RESULTS: Bacterial meningitis was identified in five cases (9%) by CSF cultures, 25 (45%) by RT-PCR and 16 (29%) by mPCR/RLB. One strain of S. epidermidis and one of E. faecalis were identified using mPCR/RLB but not by RT-PCR. In contrast, cultures identified one strain of S. pneumoniae which was missed by both PCR assays. Overall, the bacterial pathogens in 28 cases were identified with these three methods. Both RT-PCR and mPCR/RLB assays were more sensitive than bacterial culture, (p < 0.05). CONCLUSION: Our study confirmed that both RT-PCR and mPCR/RLB assays have better sensitivity than bacterial culture. They are capable of detecting the pathogens in CSF samples with negative culture results.

Sphingomonas paucimobilis: an unusual cause of meningitis-case report.

Sphingomonas paucimobilis is an aerobic gram-negative bacillus. The bacteria can cause infections, which can be devastating and, therefore, the patients need adequate and early antibiotic cover. We are presenting an interesting case of meningitis secondary to an unusual S. paucimobilis infection. This is the second case to our knowledge in the literature on meningitis due to S. paucimobilis. The 31-year-old previously healthy man presented with 2 months' history of weight loss and loss of appetite. He had fever and headache for 3 weeks. He was also speaking irrelevantly for 3 weeks. He had change of behaviour for 1 day. The patient was a farmer and worked in the soil. On examination, he was not responding to questions and was not obeying commands. Computed tomography (CT) brain with contrast revealed meningeal enhancement and cerebral oedema. Lumbar puncture was performed. Cerebrospinal fluid (CSF) opening pressure was more than 50 cm H2O. CSF analysis showed meningitis picture with raised white cell count of 210/µL (predominantly neutrophils), glucose 3.1 mmol/L, and raised protein 2.47 g/L. He was given intravenous ceftriaxone. The following day, his condition deteriorated. CSF culture grew S. paucimobilis sensitive to ceftriaxone. S. paucimobilis causes severe meningitis. This can lead to hydrocephalus, which results in a need for extraventricular drainage. A good occupational history is important with regard to finding the aetiology of serious meningitis (including rare bacteria) even before the culture result is known. Appropriate treatment can be given early and adequately to prevent mortality.

Drug resistance patterns of bacteria isolated from patients with nosocomial pneumonia at Tehran hospitals during 2009-2011.

INTRODUCTION: Nosocomial pneumonia remains an important cause of mortality and morbidity worldwide. Surveillance programs play an important role in the identification of common etiologic agents and local patterns of antimicrobial resistance. METHODOLOGY: In this study we determined the frequency and antimicrobial susceptibility of pathogens isolated from patients with nosocomial pneumonia during 2009 to 2011. RESULTS: A total of 642 bacteria were isolated from 516 suspected samples. Acinetobacter baumannii (21.1%, n = 136), was the commonest isolated pathogen followed by Pseudomonas aeruginosa (17.4%, n = 112), Staphylococcus aureus (15.8%, n = 102) and enterococci (8.4% n = 54). The most effective therapeutic agents against A. baumannii were polymyxin B (95.5% susceptible), ceftriaxone/tazobactam (72% susceptible) and levofloxacin (52.9% susceptible). Polymixin B (89.2% susceptible), ceftriaxone/tazobactam (89.2% susceptible) and piperacillin-tazobactam (80.3% susceptible) were found to be the most active agents against P. aeruginosa. Extended-spectrum beta-lactamases were detected among isolates of K. pneumoniae (45.4%) and E. coli (20.3%). Overall, the prevalence of methicillin-resistant S. aureus and vancomycin resistant enterococci were 80.4% and 40.7% respectively. Linezolid was found to be the most active antibiotic against these pathogens. The etiology of 50% of the nosocomial infection cases was polymicrobial. CONCLUSIONS: The combination of ceftriaxone/tazobactam seems to be beneficial agent against multidrug-resistant Gram-negative bacilli isolated form respiratory tract infections. The results of our study can be used for guiding appropriate empiric therapy in this geographic region.

Three cases of Capnocytophaga canimorsus meningitis seen at a regional hospital in one year.

Three cases of meningitis caused by the fastidious Gram-negative rod Capnocytophaga canimorsus have been observed at a regional hospital in 1 y. The difficulties connected with the correct diagnosis by classical culturing methods in contrast to molecular methods, as well as possible reasons for the accumulation of cases, are discussed.

Evaluation of brain tissue or cerebrospinal fluid with broadly reactive polymerase chain reaction for Ehrlichia, Anaplasma, spotted fever group Rickettsia, Bartonella, and Borrelia species in canine neurological diseases (109 cases).

BACKGROUND: Vector-transmitted microorganisms in the genera Ehrlichia, Anaplasma, Rickettsia, Bartonella, and Borrelia are commonly suspected in dogs with meningoencephalomyelitis (MEM), but the prevalence of these pathogens in brain tissue and cerebrospinal fluid (CSF) of dogs with MEM is unknown. HYPOTHESIS/OBJECTIVES: To determine if DNA from these genera is present in brain tissue and CSF of dogs with MEM, including those with meningoencephalitis of unknown etiology (MUE) and histopathologically confirmed cases of granulomatous (GME) and necrotizing meningoencephalomyelitis (NME). ANIMALS: Hundred and nine dogs examined for neurological signs at 3 university referral hospitals. METHODS: Brain tissue and CSF were collected prospectively from dogs with neurological disease and evaluated by broadly reactive polymerase chain reaction (PCR) for Ehrlichia, Anaplasma, Spotted Fever Group Rickettsia, Bartonella, and Borrelia species. Medical records were evaluated retrospectively to identify MEM and control cases. RESULTS: Seventy-five cases of MUE, GME, or NME, including brain tissue from 31 and CSF from 44 cases, were evaluated. Brain tissue from 4 cases and inflammatory CSF from 30 cases with infectious, neoplastic, compressive, vascular, or malformative disease were evaluated as controls. Pathogen nucleic acids were detected in 1 of 109 cases evaluated. Specifically, Bartonella vinsonii subsp. berkhoffii DNA was amplified from 1/6 dogs with histopathologically confirmed GME. CONCLUSION AND CLINICAL IMPORTANCE: The results of this investigation suggest that microorganisms in the genera Ehrlichia, Anaplasma, Rickettsia, and Borrelia are unlikely to be directly associated with canine MEM in the geographic regions evaluated. The role of Bartonella in the pathogenesis of GME warrants further investigation.

Community-acquired Capnocytophaga canimorsus meningitis in adults: report of one case with a subacute course and deafness, and literature review.

INTRODUCTION: An adult with community-acquired Capnocytophaga canimorsus meningitis presented with a subacute course, deafness, and a predominantly lymphocytic CSF cell count. METHODS: Eighteen reported cases of C. canimorsus meningitis in adults were analyzed. RESULTS: In about half the cases, CSF contained less than 1,000 leukocytes/microL or lymphocyte percentages 30%. These figures differ from those usually seen in meningitis caused by the classic meningeal pathogens. CONCLUSIONS: C. canimorsus should be included among the causes of sporadic lymphocytic meningitis in adults, in particular if the presentation involves deafness.