Healthcare-associated ventriculitis: current and emerging diagnostic and treatment strategies.

Introduction: Healthcare-associated ventriculitis and meningitis occur after neurosurgical procedures, is associated with an adverse outcome in the majority of patients and represent a diagnostic challenge to clinicians. As the cerebrospinal fluid (CSF) culture is the cornerstone of diagnosis, obtaining CSF studies prior to starting antibiotic therapy is key.Areas covered: This review will evaluate the incidence, risk factors, clinical presentation, diagnosis, empirical intravenous antibiotic therapy, adjunctive intrathecal therapy, microbiology, prognosis, and prevention of HCAVM. We highlight the challenges and limitations of the currently available diagnostic methods and definitions and explore novel technologies. Our review included the search for published literature until June 2020.Expert opinion: Despite available preventive measures, HCAVM continues to occur and to be independently associated with significant neurological morbidity and mortality in the majority of patients. The cornerstone of the diagnosis of HCAVM is a positive CSF culture but the microbiological yield is reduced to ~50% with prior antimicrobial therapy. Although the CSF profile is not affected by antibiotic therapy it has a fair diagnostic accuracy. Future research efforts should concentrate in identifying novel diagnostic tools such as polymerase chain reaction (PCR) or metagenomic sequencing.

Daptomycin Plasma and CSF Levels in Patients with Healthcare-Associated Meningitis.

BACKGROUND: There are currently few data concerning the cerebrospinal fluid (CSF) penetration of daptomycin in patients with healthcare-associated meningitis. This study aims (1) to better characterize the pharmacokinetics of daptomycin in humans during a 7-day intravenous (IV) therapy course, and (2) to study the penetration of daptomycin in the CSF after IV infusion at the dose of 10 mg/kg. RESULTS: In this prospective observational study, we enrolled nine patients with an implanted external ventricular drainage and a diagnosis of a healthcare-associated meningitis. Daptomycin was administered at 10 mg/kg for a maximum of 7 days. The pharmacokinetic of daptomycin was studied using a two-compartment population/pharmacokinetic (POP/PK) model and by means of a nonlinear mixed effects modeling approach. A large inter-individual variability in plasma area under the curve (Range: 574.7-1366.3 h mg/L), paralleled by high-peak plasma concentration (Cmax) (all values > 60 mg/L), was noted. The inter-individual variability of CSF-AUC although significant (range: 1.17-6.81 h mg/L) was narrower than previously reported and with a late occurrence of CSF-Cmax (range: 6.04-9.54 h). The terminal half-life between plasma and CSF was similar. tmax values in CSF did not show a high inter-individual variability, and the fluctuations of predicted CSF concentrations were minimal. The mean value for daptomycin penetration obtained from our model was 0.45%. CONCLUSIONS: Our POP/PK model was able to describe the pharmacokinetics of daptomycin in both plasma and CSF, showing that daptomycin (up to 7 days at 10 mg/kg) has minimal penetration into central nervous system. Furthermore, the observed variability of AUC, tmax and predicted concentration in CSF was lower than what previously reported in the literature. Based on the present findings, it is unlikely that daptomycin could reach CSF concentrations high enough to have clinical efficacy; this should be tested in future studies.

The Causes of Postoperative Meningitis: The Comparison of Gram-Negative and Gram-Positive Pathogens.

AIM: To determine the microbiological etiology in critically ill neurosurgical patients with nosocomial meningitis (NM) and to show the impact of Gram-negative rods and the differences between patient characteristics and the clinical and prognostic measures in Gram-negative and Gram-positive meningitis. MATERIAL AND METHODS: In this prospective, single-center study, we reviewed all adult patients hospitalized during a 12-year period and identified pathogens isolated from post-neurosurgical cases of NM. Demographic, clinical, and treatment characteristics were noted from the medical records. RESULTS: Of the 134 bacterial NM patients, 78 were male and 56 were female, with a mean age of 46±15.9 and a median age of 50 (18-80) years. One hundred and forty-one strains were isolated; 82 (58.2%) were Gram-negative, 59 (41.8%) were Grampositive. The most commonly isolated microorganism was Acinetobacter baumannii (34.8%). Comparison of mortality data shows that the patients who have meningitis with Gram-negative pathogens have higher mortality than with Gram-positives (p=0.034). The duration between surgery and meningitis was shorter in Gram-negative meningitis cases compared to others (p=0.045) but the duration between the diagnosis and death was shorter in Gram-positive meningitis cases compared to Gram-negatives (p=0.017). Cerebrospinal fluid protein and lactate levels were higher and glucose level was lower in cases of NM with Gram-negatives (p values were respectively, 0.022, 0.039 and 0.049). CONCLUSION: In NM, Gram-negative pathogens were seen more frequently; A. baumanni was the predominant pathogen; and NM caused by Gram-negatives had worse clinical and laboratory characteristic and prognostic outcome than Gram-positives.

Diagnostic Approach to Health Care- and Device-Associated Central Nervous System Infections.

Health care- and device-associated central nervous system (CNS) infections have a distinct epidemiology, pathophysiology, and microbiology that require a unique diagnostic approach. Most clinical signs, symptoms, and tests used to diagnose community-acquired CNS infections are insensitive and nonspecific in neurosurgical patients due to postsurgical changes, invasive devices, prior antimicrobial exposure, and underlying CNS disease. The lack of a standardized definition of infection or diagnostic pathway has added to this challenge. In this review, we summarize the epidemiology, microbiology, and clinical presentation of these infections, discuss the issues with existing microbiologic tests, and give an overview of the current diagnostic approach.

Prognostic value of cerebrospinal fluid lactate in meningitis in postoperative neurosurgical patients.

OBJECTIVE: To evaluate the prognostic usefulness of cerebrospinal fluid (CSF) lactate in postoperative bacterial meningitis (POBM) and to establish the optimal CSF lactate cut-off values in our population to identify POBM in neurosurgical patients. PATIENTS AND METHODS: A prospective study of postoperative neurosurgical patients with presumed and established bacterial meningitis in the Department of Neurosurgery, NIMS, Hyderabad, India, from September 2012 to December 2014. The diagnostic and prognostic values of CSF lactate have been evaluated and compared with other well-established CSF markers. All the patients who have undergone intradural cranial surgery with features of meningism have been included. RESULTS: The study included 37 patients. The CSF value of the first lumbar puncture (LP) was taken to evaluate the diagnostic value of CSF lactate. Twenty three corresponded to Group A, and 14 to Group B. The mean CSF lactate in Group A was 5.94 ± 2.36, and in Group B 4.60 ± 2.31. Subsequent LPs were performed and CSF analyzed to evaluate the prognostic value of CSF lactate. The CSF markers like neutrophil count (P = 0.003), CSF/blood glucose ratio (P = 0.012), CSF lactate (P = 0.024), lymphocyte count (P = 0.046), leukocyte count (P = 0.047) have shown their prognostic value in a descending order. CSF markers like the presence of red blood cells (P = 0.540) and proteins (P = 0.757) did not show prognostic significance. The decline in CSF lactate (content and concentration) after initiation of antibiotics correlated with subsidence of fever (P = 0.0001), decrease in neck rigidity (P = 0.022) and improvement in sensorium. They were also correlated improvement in CSF/blood glucose ratio and CSF white blood cell counts. CONCLUSIONS: In our study, CSF lactate was noted to have a dependable prognostic value in POBM. As routine CSF markers can be ambiguous in POBM, CSF lactate can be considered a better alternative for both establishing the diagnosis and prognostication.

Coagulase-negative staphylococci are associated to the mild inflammatory pattern of healthcare-associated meningitis: a retrospective study.

The epidemiology of healthcare-associated meningitis (HAM) is dominated by commensal bacteria from the skin, as coagulase-negative staphylococci (CoNS). We hypothesized that the pauci-symptomatic and mild inflammatory patterns of HAM are related to the low pathogenic state of CoNS. Our aim was to describe clinical and biological features of CoNS HAM, compared to other HAM. All consecutive patients with HAM admitted in our hospital were retrospectively included from 2007 to 2014. HAM due to CoNS were compared to HAM caused by other bacteria (controls) for clinical and laboratory patterns. Seventy-one cases of HAM were included, comprising 18 CoNS and 53 controls. Patients were not different in terms of baseline characteristics. CoNS HAM occurred later after the last surgery than controls (17 vs. 12 days, p = 0.029) and had higher Glasgow Coma Scale (GCS) score (14 vs. 13, p = 0.038). Cerebrospinal fluid (CSF) analysis revealed a lower pleocytosis (25 vs. 1340/mm3, p < 0.001), a higher glucose level (3.75 vs. 0.8 mmol/L, p < 0.001), and a lower protein level (744 vs. 1751 mg/L, p < 0.001) in the CoNS group than in the control group, respectively. HAM due to CoNS was significantly less symptomatic and less inflammatory than HAM due to other bacteria.

Antibiotic Distribution into Cerebrospinal Fluid: Can Dosing Safely Account for Drug and Disease Factors in the Treatment of Ventriculostomy-Associated Infections?

Ventriculostomy-associated infections, or ventriculitis, in critically ill patients are associated with considerable morbidity. Efficacious antibiotic dosing for the treatment of these infections may be complicated by altered antibiotic concentrations in the cerebrospinal fluid due to variable meningeal inflammation and antibiotic properties. Therefore, doses used to treat infections with a higher degree of meningeal inflammation (such as meningitis) may often fail to achieve equivalent exposures in patients with ventriculostomy-associated infections such as ventriculitis. This paper aims to review the disease burden, infection rates, and common pathogens associated with ventriculostomy-associated infections. This review also seeks to describe the disease- and drug-related factors that influence antibiotic distribution into cerebrospinal fluid and provide a critical appraisal of current dosing of antibiotics commonly used to treat these types of infections. A Medline search of relevant articles was conducted and used to support a review of cerebrospinal fluid penetration of vancomycin, including critical appraisal of the recent paper by Beach et al. recently published in this journal. We found that in the intensive care unit, ventriculostomy-associated infections are the most common and serious complication of external ventricular drain insertion and often result in prolonged patient stay and increased healthcare costs. Reported infection rates are extremely variable (between 0 and 45%), hindered by the inherent diagnostic difficulty. Both Gram-positive and Gram-negative organisms are associated with such infections and the rise of multi-drug-resistant pathogens means that effective treatment is an ongoing challenge. Disease factors that may need to be considered are reduced meningeal inflammation and the presence of critical illness; drug factors include physiochemical properties, degree of plasma-protein binding, and affinity to active transporter proteins present in the blood-cerebrospinal fluid barrier. The relationship between cerebrospinal fluid antibiotic exposures in the setting of ventriculostomy-associated infection and clinical response has not been fully elucidated for many of the antibiotics commonly used in its treatment. More thorough and clinically relevant investigations are needed to better define blood pharmacokinetic/pharmacodynamics targets and optimal therapeutic exposures for treatment of ventriculostomy-associated infections. It is hoped that this future research will be able to provide clearer recommendations for clinicians frequently faced with dosing-related dilemmas when treating patients with these challenging infections.

Prognostic Impact of Health Care-Associated Meningitis in Adults with Intracranial Hemorrhage.

BACKGROUND: Health care-associated meningitis and ventriculitis (HCAMV) occurs in adults with intracranial hemorrhage (ICH) and is associated with high rates of morbidity and mortality, but the prognostic impact of this infectious complication in a controlled matched study of ICH is unknown. METHODS: We conducted a case-control study of adult patients with ICH and HCAMV at a large tertiary care hospital in Houston, Texas, from 2003 to 2016. Cases were defined as patients with ICH and HCAMV as documented by a positive cerebrospinal fluid culture. Controls were defined as patients with ICH without evidence of HCAMV. An adverse clinical outcome was defined as a Glasgow Outcome Scale score of ≤4. RESULTS: This study included 120 patients with ICH; 40 patients also had HCAMV, whereas 80 patients had ICH with no evidence of HCAMV. Cases and controls were appropriately matched by age, Glasgow Coma Scale score, and Acute Physiology and Chronic Health Evaluation II score (P > 0.05). Patients with ICH and meningitis had more comorbidities, higher rates of abnormal neurologic examination, hypoglycorrhachia, and elevated cerebrospinal fluid lactate levels (P < 0.05). Adverse clinical outcomes were greater in patients with HCAMV and ICH than in patients with ICH alone (83% vs. 30%; P < 0.001). On logistic regression analysis, independent risk factors associated with an adverse outcome were HCAMV and mechanical ventilation (P < 0.05). CONCLUSIONS: HCAMV has a significant prognostic impact in adults with ICH.

Clinical and Laboratory Characteristics for the Diagnosis of Bacterial Ventriculitis After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The diagnosis of nosocomial bacterial ventriculitis in patients with subarachnoid hemorrhage (SAH) can be challenging. METHODS: We performed a retrospective study on the diagnostic accuracy of clinical and laboratory characteristics for the diagnosis of bacterial ventriculitis in 209 consecutive patients with an aneurysmal SAH admitted in a tertiary referral center from 2008 to 2010. Diagnostic value of clinical characteristics and inflammatory indexes in CSF and blood were determined for three diagnostic categories: (1) no suspicion for bacterial ventriculitis; (2) clinical suspicion for bacterial ventriculitis, defined as initiation of empirical antibiotic treatment for ventriculitis, but negative CSF cultures; and (3) CSF culture-positive bacterial ventriculitis. RESULTS: Empirical antibiotics for suspected ventriculitis was initiated in 48 of 209 (23 %) patients. CSF cultures were positive in 11 (5 %) patients. Within the group of suspected ventriculitis, only longer duration of CSF drainage and lower CSF red blood cell counts predicted for culture positivity. None of the other clinical features or inflammatory indexes in CSF and blood were associated with culture-proven bacterial ventriculitis. CONCLUSIONS: Nosocomial bacterial ventriculitis in patients with aneurysmal SAH is often suspected but confirmed by culture in a minority of cases. Improvement of diagnostics for nosocomial bacterial ventriculitis in patients with aneurysmal SAH is needed.

Risk Factors for Infections Related to Lumbar Drainage in Spontaneous Subarachnoid Hemorrhage.

BACKGROUND: A solid knowledge associated with lumbar drainage (LD)-related infections in spontaneous subarachnoid hemorrhage (SAH) patients is necessary and that would be useful in taking effective measures to cope with this complication. We aimed to describe incidence rates and risk factors associated with LD-related infections in SAH patients. METHODS: A retrospective review was performed on SAH patients who underwent LD between July 2010 and August 2015. Patient charts were reviewed to retrieve demographic, clinical, and laboratory data. LD-related infections were defined based on culture results of cerebrospinal fluid in combination with clinical symptoms. Infection rates were calculated, and a logistic regression model was developed to identify risk factors. RESULTS: A total of 629 SAH patients (25-82 years age range, 42.8 % male) were treated with LD in the period. LD-related infections were identified in 36 patients (5.7 %). Longer duration of LD (≥4 days: p = 0.0037) and puncture site leakage (p < 0.0001) appeared to be risk factors for infection. The infection rate increased with length of the hospital stay (16-20 days: p = 0.0032; ≥21 days: p = 0.0007). 84.6 % of the isolated bacteria were Gram-positive, and the most commonly associated pathogens were Methicillin-resistant coagulase-negative Staphylococcus (MRCNS, 61.5 %). CONCLUSIONS: The patients with LD for more than 4 days or with puncture site leakage had more risk of infection. Infected patients were more likely to stay longer in the hospital. MRCNS were identified as the most frequent causal pathogens. And the use of antibiotics during LD did not appear to reduce the risk of infection.

Hepatocyte growth factor in cerebrospinal fluid differentiates community-acquired or nosocomial septic meningitis from other causes of pleocytosis.

BACKGROUND: Due to anatomical restrictions, the inflammatory response to intracerebral bacterial infections exposes swollen brain tissues to pressure and ischemia, resulting in life-threatening damage. Rapid diagnosis and immediate empirical antibiotic therapy is highly important. However, diagnosing meningitis in patients after neurosurgery is complicated, due to brain tissue damage and changes in cerebrospinal fluid (CSF) caused by surgery. Hepatocyte growth factor (HGF) is a local, acute-phase protein with healing properties. Previous studies on community-acquired septic meningitis reported high levels of intrathecally produced HGF. The present study focused on nosocomial meningitis in assessing the levels of HGF in the CSF. METHODS: HGF concentrations (ELISA) and HGF binding to receptors; c-Met receptor and heparan sulfate proteoglycan were determined in CSF samples (surface plasmon resonance). CSF samples from patients with community-acquired or nosocomial meningitis (217 samples from 135 patients) were compared to those from controls without signs of cerebral nervous system involvement (N = 36) and patients with Alzheimer's disease (N = 20). RESULTS: Compared to samples from patients that had undergone neurosurgery and had other infectious diseases, CSF samples from patients with nosocomial meningitis had significantly higher HGF concentrations (p < 0.001) and binding affinity to c-Met (p < 0.001) and HSPG (p = 0.043) receptors. The sensitivity and specificity to identify nosocomial septic meningitis were 69.7 and 93.4%, respectively. The HGF concentration and binding affinity to HGF receptors were significantly higher in CSF from patients with community-acquired septic meningitis compared to patients with aseptic (viral and subacute) meningitis as well as controls (p < 0.001). The sensitivity and specificity to identify community-acquired septic meningitis were 95.4 and 95.7%, respectively. DISCUSSION: In febrile nosocomial infections that occurred post neurosurgery, HGF assessment could substantially improve the differentiation of meningitis from other infections and therefore might be a tool for rapid diagnosis, limiting injuries and guiding antibiotic therapy.

Clinical, biological, and microbiological pattern associated with ventriculostomy-related infection: a retrospective longitudinal study.

BACKGROUND: Our aim was to describe the pattern of ventriculostomy-related infection (VRI) development using a dynamic approach. STUDY DESIGN: Retrospective longitudinal study. METHODS: We analyzed the files of 449 neurosurgical patients who underwent placement of external ventricular drain (EVD). During the study period, CSF sampling was performed on a daily base setting. VRI was defined as a positive CSF culture resulting in antibiotic treatment. For VRI patients, we arbitrary defined day 0 (D0) as the day antibiotic treatment was started. In these patients, we compared dynamic changes in clinical and biological parameters at four pre-determined time points: (D-4, D-3, D-2, D-1) with those of D0. For all CSF-positive cultures, we compared CSF biochemical markers' evolution pattern between VRI patients and the others, considered as a control cohort. RESULTS: Thirty-two suffered from VRI. Peripheral white blood cell count did not differ between D-4-D0. Median body temperature, CSF cell count, median Glasgow Coma Scale, CSF protein, and glucose concentrations were significantly different between D-4, D-3, D-2, and D0. At D0, 100 % of CSF samples yielded organisms in culture. The physician caring for the patient decided to treat VRI based upon positive CSF culture in only 28 % (9/32) of cases. In the control cohort, CSF markers' profile trends to normalize, while it worsens in the VRI patients. CONCLUSIONS: We showed that clinical symptoms and biological abnormalities of VRI evolved over time. Our data suggest that VRI decision to treat relies upon a bundle of evidence, including dynamic changes in CSF laboratory exams combined with microbiological analysis.

The combination of decoy receptor 3 and soluble triggering receptor expressed on myeloid cells-1 for the diagnosis of nosocomial bacterial meningitis.

BACKGROUND: Early diagnosis and appropriate antibiotic treatment can significantly reduce mortality of nosocomial bacterial meningitis. However, it is a challenge for clinicians to make an accurate and rapid diagnosis of bacterial meningitis. This study aimed at determining whether combined biomarkers can provide a useful tool for the diagnosis of bacterial meningitis. METHODS: A retrospective study was carried out. Cerebrospinal fluid (CSF) levels of decoy receptor 3 (DcR3) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: The patients with bacterial meningitis had significantly elevated levels of the above mentioned biomarkers. The two biomarkers were all risk factors with bacterial meningitis. The biomarkers were constructed into a "bioscore". The discriminative performance of the bioscore was better than that of each biomarker, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.842 (95% confidence intervals (CI) 0.770-0.914; p< 0.001). CONCLUSIONS: Combined measurement of CSF DcR3 and sTREM-1 concentrations improved the prediction of nosocomial bacterial meningitis. The combined strategy is of interest and the validation of that improvement needs further studies.

Validation of an automated surveillance approach for drain-related meningitis: a multicenter study.

OBJECTIVE Manual surveillance of healthcare-associated infections is cumbersome and vulnerable to subjective interpretation. Automated systems are under development to improve efficiency and reliability of surveillance, for example by selecting high-risk patients requiring manual chart review. In this study, we aimed to validate a previously developed multivariable prediction modeling approach for detecting drain-related meningitis (DRM) in neurosurgical patients and to assess its merits compared to conventional methods of automated surveillance. METHODS Prospective cohort study in 3 hospitals assessing the accuracy and efficiency of 2 automated surveillance methods for detecting DRM, the multivariable prediction model and a classification algorithm, using manual chart review as the reference standard. All 3 methods of surveillance were performed independently. Patients receiving cerebrospinal fluid drains were included (2012-2013), except children, and patients deceased within 24 hours or with pre-existing meningitis. Data required by automated surveillance methods were extracted from routine care clinical data warehouses. RESULTS In total, DRM occurred in 37 of 366 external cerebrospinal fluid drainage episodes (12.3/1000 drain days at risk). The multivariable prediction model had good discriminatory power (area under the ROC curve 0.91-1.00 by hospital), had adequate overall calibration, and could identify high-risk patients requiring manual confirmation with 97.3% sensitivity and 52.2% positive predictive value, decreasing the workload for manual surveillance by 81%. The multivariable approach was more efficient than classification algorithms in 2 of 3 hospitals. CONCLUSIONS Automated surveillance of DRM using a multivariable prediction model in multiple hospitals considerably reduced the burden for manual chart review at near-perfect sensitivity.

The causes and treatment outcomes of 91 patients with adult nosocomial meningitis.

BACKGROUND/AIMS: Frequent pathogens of nosocomial meningitis were investigated and the adequacy of empiric antibiotic therapy was assessed. Outcomes of nosocomial meningitis were also evaluated. METHODS: Ninety-one patients, who were diagnosed and treated for nosocomial meningitis at a single tertiary hospital in Daegu, Korea for 10 years, were included. Medical record and electronic laboratory data on the causative pathogens, antibiotics used, and outcomes were retrospectively investigated. RESULTS: Coagulase-negative Staphylococcus (40.9%) was the most common pathogen, followed by Acinetobacter (32.5%). Both were cultured as a single organism in cerebrospinal fluid (CSF). Seventy-eight patients (85.7%) had infections related to external ventricular drains (EVD). The most common empirical antibiotics were extended-spectrum beta-lactam antibiotics plus vancomycin (35/91, 38.6%). Of the 27 patients who had cultured Acinetobacter in CSF, 10 (37%) were given the wrong empirical antibiotic treatment. Seven of the 27 patients (26.9%) with cultured Acinetobacter died, and overall mortality of the 91 patients was 16.5%. In the multivariate analysis, the presence of combined septic shock (p < 0.001) and a persistent EVD state (p = 0.021) were associated with a poor prognosis. CONCLUSIONS: Acinetobacter is one of the leading pathogens of nosocomial meningitis and may lead to inadequate coverage of empiric antibiotic therapy due to increasing resistance. An EVD should be removed early in cases of suspected nosocomial meningitis, and carbapenem might be required for the poor treatment response.

[Stroke-induced nosocomial pneumonia in the acute period of cerebral hemorrhage: clinical pathogenic and age-associated aspects].

The article presents the clinical features of stroke-induced nosocomial pneumonia and interleukin-1alpha level monitoring in serum and cerebrospinal fluid of 100 patients with cerebral hemorrhage on the 1st, 3rd and 10th day. The authors show that 66% of patients with cerebral hemorrhage develop nosocomial pneumonia since the end of 2nd up to 5th day of conservative hospital treatment, more frequently in the serious cases with high level of neurological deficiency. The most important risk factors of stroke-induced nosocomial pneumonia are chronic focal infection, diabetes mellitus, cardiac failure, smoking, obesity. Since the first day of stroke the interleukin-1alpha level both in serum and cerebrospinal fluid exceeds 25-30 times its content in healthy people and increases more in the presence of nosocomial pneumonia. Interleukin-1alpha level can serve as an early risk marker of lethal outcome in patients with cerebral hemorrhage.

Association of Bacillus cereus infection with contaminated alcohol prep pads.

BACKGROUND: Bacillus species have caused healthcare-associated outbreaks of invasive disease as well as pseudo-outbreaks. We report an outbreak investigation of blood cultures positive for Bacillus cereus associated with alcohol prep pads (APPs) contaminated with B. cereus and Bacillus species resulting in a rapid internal product recall and subsequent international product recall. DESIGN: Epidemiologic and microbiologic outbreak investigation. SETTING: A 300-bed tertiary care children's hospital in Aurora, Colorado. PATIENTS: Patients with blood or cerebrospinal fluid cultures positive for B. cereus. METHODS: Three patients with blood cultures positive for B. cereus were identified in late 2010. Breaches in procedural and surgical techniques, common interventions, and products were explored. The following 3 common products were cultured: sterile saline syringes, chlorhexidine/alcohol skin preparation solution, and APPs. Repetitive sequence-based polymerase chain reaction (Rep-PCR) was used to compare isolates obtained from patients and from APPs and was confirmed by independent pulsed-field gel electrophoresis. RESULTS: There appeared to be a significant increase in blood cultures positive for B. cereus during 2009-2010. B. cereus and other Bacillus species were cultured from the internal contents of 63.3% of APPs not labeled as sterile, and 8 of the 10 positive lots were manufactured after 2007. None of the isolates obtained from the patients matched strains isolated from the APPs. However, some lots of APPs had strains that were indistinguishable from one another. CONCLUSIONS: APPs that were not labeled as sterile were contaminated with Bacillus species. The product was immediately recalled internally and replaced with APPs from another manufacturer that were labeled as sterile. On January 3, 2011, the manufacturer voluntarily recalled its APPs. Healthcare facilities, healthcare providers, and users of APPs should avoid the use of APPs not specifically labeled as sterile.

In vitro antifungal activities of amphotericin B, 5-fluorocytosine, fluconazole and itraconazole against Cryptococcus neoformans isolated from cerebrospinal fluid and blood from patients in Serbia.

Recently, geographic variations in resistance to agents commonly used in the treatment of cryptococcosis have been reported. Therefore, the antifungal susceptibilities of 31 clinical isolates of Cryptococcus neoformans, collected in Serbia during 10-year period, were investigated. Strains were isolated from cerebrospinal fluid (n=28) and blood (n=3), from patients with AIDS (n=26), lymphoma (n=4) and kidney transplant recipient (n=1). The minimal inhibitory concentrations (MICs) of amphotericin B, 5-fluorocytosine, fluconazole and itraconazole were determined by the E-test(®) method. The isolates were highly susceptible to amphotericin B (100% susceptibility at MIC<0.5 µg/mL) and 5-fluorocytosine (87.1% susceptibility at MIC ≤ 4 µg/mL). Geometric mean MIC of amphotericin B and 5-fluorocytosine were 0.102 µg/mL and 0.396 µg/mL, respectively. Fluconazole exhibited the lowest activity in vitro (48.4% susceptibility at MIC ≤ 8 µg/mL) with a significant resistance rate. The activity of itraconazole was also decreased (48.4% susceptibility at MIC ≤ 0.25 µg/mL). The geometric mean MIC of fluconazole stood at 15.14 µg/mL and of itraconazole was 0.144 µg/mL. Cross-resistance among azoles was not common (3.2%), but the parallel increase in fluconazole and itraconazole MIC has been observed (P<0.01). The low rate of susceptibility to fluconazole stresses the need for active antifungal surveillance of C. neoformans and of the corresponding data from different geographic regions.