[Milk-alkali syndrome: a careful history is crucial in diagnosing hypercalcemia]. / Melk-alkalisyndroom.

BACKGROUND: Milk-alkali syndrome is a rare cause of hypercalcemia in the Netherlands, due to ingestion of large amounts of calcium and absorbable alkali. CASE DESCRIPTION: A 38-year-old female patient was admitted with severe stomach pain, vomiting and weight loss. Laboratory results showed hypercalcemia and acute kidney injury. We initially suspected that the hypercalcemia was related to primary hyperparathyroidism, a malignancy with bone metastasis or a granulomatous disease. Gastroduodenoscopy, however, revealed a duodenal ulcer, which turned out to be Helicobacter pylori-related. A thorough history revealed that the patient had consumed large amounts of milk and antacids to relieve symptoms of heartburn. In light of this history, milk-alkali syndrome was diagnosed. CONCLUSION: The case aims to underline the importance of a thorough history in patients with hypercalcemia. The use of over-the-counter medications and dairy products should be evaluated in all patients presenting with hypercalcemia.

Guidance of empirical antimicrobial therapy by surveillance cultures in high-risk neutropenic patients: a retrospective cohort study.

BACKGROUND: In neutropenic patients, bloodstream infections (BSI) significantly contribute to morbidity and mortality. Appropriate empirical antibiotic therapy (EAT) of BSI is essential, at the same time overconsumption of very broad-spectrum antibiotics should be avoided. We investigated: (1) whether surveillance cultures can predict BSI with third-generation cephalosporin -resistant Enterobacterales and Pseudomonas aeruginosa (3GC-R), (2) the effect of inappropriate empirical antimicrobial therapy (IEAT) on clinical outcome and (3) the potential reduction of carbapenem use when using surveillance cultures to guide therapy. METHODS: Retrospective study of adult patients with haematological malignancies with febrile episodes during chemotherapy-induced high-risk neutropenia in whom surveillance cultures were collected weekly. IEAT was defined as the absence of in vitro susceptibility of blood-isolates to the administered EAT. Clinical outcome (ICU admission and death) was evaluated within 30 days. RESULTS: A total of 673 febrile episodes occurred among 372 high-risk neutropenic patients. BSI was present in 20.1% (135/673), of which 25.9% (35/135) were due to Enterobacterales and P. aeruginosa. Of these, 17/35 were 3GC-R and 70.6% (12/17) were preceded by 3GC-R colonization. Negative predictive value of surveillance cultures for 3GC-R BSI was 99.1%. IEAT due to (3GC-R) BSI was not significantly associated with clinical outcome. Using surveillance cultures to guide EAT could potentially reduce carbapenem use by 82.8%, when compared to standard EAT with carbapenem. CONCLUSIONS: This retrospective analysis shows that in patients with high-risk neutropenia, surveillance cultures can potentially reduce the use of carbapenems with infrequent IEAT for 3GC-R BSI and no negative impact on clinical outcome.

Third-generation cephalosporin resistant gram-negative bacteraemia in patients with haematological malignancy; an 11-year multi-centre retrospective study.

OBJECTIVES: Among patients with haematological malignancy, bacteraemia is a common complication during chemotherapy-induced neutropenia. Resistance of gram-negative bacteria (GNB) to third-generation cephalosporins (3GC) is increasing. In order to explore the value of using surveillance cultures to guide empirical treatment e.g. choosing between carbapenem versus ceftazidime- we aimed to assess the distribution of pathogens causing bacteraemia in patients with haematological malignancy, and the proportion of 3GC-resistant GNB (3GC-R GNB) bacteraemia that was preceded by 3GC-R GNB colonization. METHODS: Using 11 years of data (2008-2018) from the Dutch national antimicrobial resistance surveillance system, we assessed the prevalence of 3GC-R GNB in episodes of bacteraemia, and the proportion of 3GC-R GNB bacteraemia that was preceded by 3GC-R GNB colonization. Colonization was defined as availability of any GNB surveillance isolate in the year before, independent of the causative micro-organism (time-paired isolates). RESULTS: We included 3887 patients, representing 4142 episodes of bacteraemia. GNB were identified in 715/4142 (17.3%), of which 221 (30.9%) were 3GC-R GNB. In 139 of these 221 patients a time-paired surveillance culture was available. In 76.2% (106/139) of patients these surveillance cultures already showed 3GC-R GNB isolates in the year prior to the culture date of the 3GC-R GNB positive blood isolate. CONCLUSIONS: This multi-centre study shows that in patients with haematological malignancy, the majority of 3GC-R GNB bacteraemia is preceded by 3GC-R GNB colonization. Prospective clinical studies are needed to assess the safety and benefits of the use of surveillance-cultures to guide empirical therapy to restrict the empirical use of carbapenems in this population.

The impact of the updated EORTC/MSG criteria on the classification of hematological patients with suspected invasive pulmonary aspergillosis.

OBJECTIVES: Our aim was to evaluate the effect of the updated European Organization for Research and Treatment of Cancer (EORTC) and Mycoses Study Group 2019 definitions for invasive pulmonary aspergillosis (IPA) on patient classification and the related all-cause 12-week mortality. METHODS: In this retrospective cohort study from our tertiary care centre, we reclassified patients with haematological malignancy who underwent bronchoalveolar lavage between 2014 and 2019 for suspected IPA using the novel EORTC 2019 criteria. We performed receiver operating characteristic curve analysis to define the optimal cut-off for positive PCR and galactomannan and present survival analyses and their possible association with these diagnostic criteria through post hoc comparisons with log rank and Cox regression. RESULTS: From 323 episodes of suspected IPA in 282 patients, 73 were reclassified: 31 (42.5%) from possible to probable IPA, 5 (6.8%) from EORTC criteria not met to probable IPA, and 37 (50.7%) from EORTC criteria not met to possible IPA. Probable IPA increased therefore 11.1% (64/323, 19.8% to 100/323, 30.9%), mostly due to positive PCR (31/36, 86.1%). There was no difference in mortality between newly defined possible and probable IPA (log rank p = 0.950). Mortality was higher in probable cases with lower cycle thresholds (Ct values) versus higher Ct values (p = 0.004). Receiver operating characteristic curve analysis showed an optimal Ct value cut-off of 36.8 with a sensitivity of 75% (95% CI 64.9%-85.1%) and a specificity of 61.7% (95% CI 53.5-69.9) for 12-week mortality. DISCUSSION: The new EORTC criteria led to 11.1% more probable IPA diagnoses, mostly due to Aspergillus PCR. Restricting positive PCR to below a certain threshold might improve the discrimination of the new EORTC IPA categories for mortality.

Short communication: high rates of thymidine analogue mutations and dual-class resistance among HIV-infected Ugandan children failing first-line antiretroviral therapy.

HIV-infected children are at high risk of acquiring drug-resistant viruses, which is of particular concern in settings where antiretroviral drug options are limited. We aimed to assess resistance patterns and predict viral drug susceptibility among children with first-line antiretroviral therapy (ART) failure in Uganda. A cross-sectional analysis of children switching ART regimens due to first-line failure was performed at three clinical sites in Uganda. HIV-RNA determination and genotypic resistance testing on all specimens with HIV-RNA >1,000 copies/ml were performed. Major drug resistance mutations were scored using the 2011 International Antiviral Society-USA list. The Stanford algorithm was used to predict drug susceptibility. At the time of switch, 44 genotypic resistance tests were available for 50 children. All children harbored virus with nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance [95% confidence interval (CI) 92-100%] and NRTI resistance was present in 98% (95% CI 88-100%). Forty-six percent (95% CI 30-61%) of children harbored ≥2 thymidine analog mutations. M184V was identified as the only NRTI mutation in 27% (95% CI 15-43%). HIV susceptibility to NRTIs, with the exception of tenofovir, was reduced in ≥60% of children. Ugandan children experiencing first-line ART failure in our study harbored high rates of dual-class and accumulated HIV drug resistance. Methods to prevent treatment failure, including adequate pediatric formulations and alternative second-line treatment options, are urgently needed.

Immune dysfunction in HIV-seronegative, Cryptococcus gattii meningitis.

The pathophysiology of meningitis caused by Cryptococcus gattii in apparently immunocompetent individuals remains unclear. We measured multiple cytokines in CSF from a HIV-seronegative, apparently immunocompetent, Thai patient with C. gattii meningitis, over the first 2 weeks of antifungal therapy. Levels of proinflammatory IFN-gamma, TNF-alpha, and IL-6 were very low compared to patients with HIV-related Cryptococcus neoformans meningitis and of IL-10 very high. While patients with C. gattii meningitis may be a heterogeneous group, these data suggest in this case a maladapted immune response to cryptococcal exposure had allowed progression to clinical cryptococcal disease.