Cefazolin versus anti-staphylococcal penicillins for treatment of methicillin-susceptible Staphylococcus aureus bacteraemia: a narrative review

BackgroundAnti-staphylococcal penicillins (ASPs) are recommended as first-line agents in methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. Concerns about their safety profile have contributed to the increased use of cefazolin. The comparative clinical effectiveness and safety profile of cefazolin versus ASPs for such infections remain unclear. Furthermore, uncertainty persists concerning the use of cefazolin due to controversies over its efficacy in deep MSSA infections and its possible negative ecological impact.AimsThe aim of this narrative review was to gather and balance available data on the efficacy and safety of cefazolin versus ASPs in the treatment of MSSA bacteraemia and to discuss the potential negative ecological impact of cefazolin.SourcesPubMed and EMBASE electronic databases were searched up to May 2017 to retrieve available studies on the topic.ContentsAlthough described in vitro and in experimental studies, the clinical relevance of the inoculum effect during cefazolin treatment of deep MSSA infections remains unclear. It appears that there is no significant difference in rate of relapse or mortality between ASPs and cefazolin for the treatment of MSSA bacteraemia but these results should be cautiously interpreted because of the several limitations of the available studies. Compared with cefazolin, there is more frequent discontinuation for adverse effects with ASP use, especially because of cutaneous and renal events. No study has evidenced any change in the gut microbiota after the use of cefazolin.ImplicationsBased on currently available studies, there are no data that enable a choice to be made of one antibiotic over the other except in patients with allergy or renal impairment. This review points out the need for future prospective studies and randomized controlled trials to better address these questions.     

Comparative outcomes of cefazolin versus antistaphylococcal penicillins in methicillin-susceptible Staphylococcus aureus infective endocarditis: a post hoc analysis of a prospective multicentre French cohort study

ObjectivesCurrent guidelines recommend cefazolin as an alternative to antistaphylococcal penicillins (ASPs) in methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis despite the lack of comparative study. The objective of this study was to evaluate the comparative outcomes of cefazolin vs. ASPs in MSSA infective endocarditis.MethodsThis was a retrospective analysis of an observational multicentre cohort study using prospectively collected data from patients with MSSA endocarditis confirmed by endocarditis team and treated either with cefazolin or ASPs between July 2013 and December 2018. Patients were excluded if they received both treatments. The primary outcome was 90-day all-cause mortality.ResultsOf 210 patients included, 53 patients (25.2%) received cefazolin and 157 (74.8%) received ASPs. The overall 90-day mortality rate was 27.6% (58/210 patients), 24.5% (13/53) in the cefazolin group vs. 28.7% (45/157) in the ASP group (p 0.561). Premature antimicrobial discontinuation due to adverse events occurred less frequently with cefazolin than with ASPs (0/53 vs. 13/157 patients; p 0.042). In multivariate analysis, there was no difference in 90-day mortality between cefazolin and ASPs (adjusted odds ratio (aOR), 1.2; 95% confidence interval (CI), 0.49–2.91; p 0.681), while age (aOR, 1.06; 95% CI, 1.03–1.09; p < 0.001), Charlson comorbidity index (aOR, 1.18; 95% CI, 1.02–1.36 p 0.023), cerebral embolism (aOR, 2.83; 95% CI, 1.33–6.14; p 0.007) and intensive care unit admission (aOR, 4.16; 95% CI, 1.89–9.59; p 0.001) were factors significantly associated with higher mortality.ConclusionsCefazolin seems to be a possible alternative to ASPs in MSSA endocarditis. More studies are needed to confirm these results and determine which treatment should be recommended as first-line therapy.     

Comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus bacteraemia: a prospective multicentre cohort study in Korea

ObjectivesNo randomized controlled trials have evaluated the comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia.MethodsA prospective observational cohort study including all S. aureus bacteraemia was conducted at 10 hospitals. Patients (≥15 years) with MSSA bacteraemia who received cefazolin or nafcillin as definitive antibiotics were included. The rates of treatment failure (premature discontinuation of antibiotics because of adverse effects, switching of antibiotics because of clinical failure, all-cause mortality within 1 month, or recurrence) were compared between the cefazolin and nafcillin groups. Propensity score matching analyses were performed to balance the factors influencing the selection of antibiotics.ResultsAmong the 242 included cases, the bones and joints (36.8%) were the most common sites of infection and 60.7% of the patients had sepsis. The overall treatment failure rate was 43.8% (106/242). All-cause mortality within 1 month was 6.2% (15/242). After propensity score matching, the treatment failure rate of cefazolin was lower than that of nafcillin (30.4% (24/79) vs. 49.4% (39/79), p 0.015) because of a higher rate of discontinuation caused by adverse events. When the data were limited to patients with sepsis, the treatment failure rates of both groups were not significantly different. Approximately 22% (24/110) of MSSA isolates exhibited a cefazolin-inoculum effect (CIE) that had significant impact on the failure rate and mortality of the cefazolin group.ConclusionsCefazolin might be recommended as an adequate and better-tolerated treatment for MSSA bacteraemia in the absence of CIE.     

Impact of antimicrobial treatment duration on outcome of Staphylococcus aureus bacteraemia: a cohort study

ObjectivesTo assess the outcome of Staphylococcus aureus bacteraemia (SAB) according to factors associated with necessity for longer treatment in conjunction with the duration of treatment.MethodsWe prospectively collected the data of patients with SAB consecutively during 12 to 39 months from 11 hospitals. If multiple episodes of SAB occurred in one patient, only the first episode was enrolled. Factors associated with necessity for longer treatment were defined as follows: persistent bacteraemia, metastatic infection, prosthesis and endocarditis. If any of the factors were present, then the case was defined as longer antibiotic treatment warranted (LW) group; those without any factors were defined as shorter antibiotic treatment sufficient (SS) group. Poor outcome was defined as a composite of 90-day mortality or 30-day recurrence. Duration of antibiotic administration was classified as <14 or ≥14 days in the SS group and <28 or ≥28 days in the LW group.ResultsAmong 2098 cases, the outcome was analysed in 1866 cases, of which 591 showed poor outcome. The SS group accounted for 964 cases and the LW group for 852. On multivariate analysis, age over 65 years, pneumonia, higher Sequential Organ Failure Assessment (SOFA) score and chronic liver diseases were risk factors for poor outcome. Administration of antibiotics less than the recommendation was associated with poor outcome, but this significance was observed only in the LW group (adjusted odds ratio = 1.68; 95% confidence interval, 1.00–2.83; p 0.05).ConclusionsInappropriately short antibiotic treatment was associated with poor outcome in the LW group. Vigilant evaluation for risk factors to determine the duration of treatment may improve the outcome among patients with SAB.     

Complicated and uncomplicated S. aureus bacteraemia: an international Delphi survey among infectious diseases experts on definitions and treatment

ObjectivesClassification of Staphylococcus aureus bacteraemia (SAB) as ‘complicated’ or ‘uncomplicated’ and management of both is based on low-quality evidence. The aim of the study was to determine the degree of agreement among infectious diseases physician experts in the management of patients with SAB.MethodsA stepwise RAND-modified Delphi procedure with two questionnaire rounds was performed. Four aspects of management in 22 clinical scenarios were addressed: (a) classification of SAB episodes; (b) value of combination therapy; and (c) timing of and (d) preferred antibiotics for oral stepdown therapy.ResultsOut of 90 approached experts, 33 (36.7%) from 14 different countries and 5 continents consented to participate. The experts considered any of the discussed implanted foreign material (with no evidence of infection), except for coronary artery stents, as relevant to the classification of a complicated SAB episode. Concerning antibiotic combination therapy, the experts strongly agreed that combination therapy with rifampicin is only relevant in patients with prosthetic valve endocarditis and prosthetic joint infection. The experts considered an oral stepdown therapy in patients with an uncomplicated SAB within 14 days and only thereafter in patients with a complicated SAB episode, but never in patients with prosthetic valve endocarditis. No single antibiotic of choice for oral stepdown therapy could be identified, neither for infections with methicillin-resistant S. aureus nor methicillin-susceptible S. aureus.DiscussionThe Delphi survey can help physicians in their day-to-day decision-making process, and it reveals open questions that must be investigated by further studies.     

Association between treatment duration and mortality or relapse in adult patients with Staphylococcus aureus bacteraemia: a retrospective cohort study

ObjectivesThe aim was to evaluate the effect of duration of therapy (DOT) on mortality and relapse for patients with Staphylococcus aureus bacteraemia (SAB).MethodsWe performed a retrospective single-centre cohort study including adult patients with SAB. We determined the association between DOT (≤14 days versus >14 days) and mortality by adjusted hazard ratios (aHR) and 95% confidence intervals through Cox regression adjusted for immortal-time bias and confounding by indication, stratified by presence of complicated SAB (any of: endocarditis, implant, duration of SAB >2 days, fever >3 days). The primary outcome was 90-day all-cause mortality, and the secondary outcome was 90-day relapse.ResultsBetween January 2010 and December 2015, we included 530 patients, of whom 94 out of 530 (17.7%) had methicillin-resistant SAB and 305 out of 530 (57.6%) had complicated SAB. Ninety-day mortality was 27.0% (143/530), with no significant trend across the study period; median time to death was 17 days (interquartile range (IQR) 8–30) after onset of SAB. Median DOT was 20 days (IQR 13–39). Patients with complicated SAB had significantly reduced mortality with DOT >14 days (aHR 0.32, 95% CI 0.16–0.64). DOT was not associated with mortality in patients with uncomplicated SAB (aHR 0.85; 0.41–1.78). Eighteen (18/530) patients (3.4%) relapsed; on univariate analysis, DOT was not associated with relapse (HR 1.01; 0.97–1.06).ConclusionsDOT >14 days is associated with higher survival in patients with complicated SAB, but not for patients with uncomplicated SAB. No association was found for relapse, but 90-day relapse was very low in this cohort. Importantly, 90-day mortality remained high across the study period.     

Vancomycin minimum inhibitory concentration,host comorbidities and mortality in Staphylococcus aureus bacteraemia

We reported an association between elevated vancomycin MIC and 30-day mortality in patients with Staphylococcus aureus bacteraemia (SAB), including patients with methicillin-susceptible S. aureus (MSSA) treated with flucloxacillin. A detailed analysis of comorbidities and disease severity scores in the same cohort of patients was performed to ascertain if unknown clinical parameters may have influenced these results. The association between elevated vancomycin MIC and 30-day mortality in SAB remained significant (p 0.001) on multivariable logistic regression analysis even when accounting for clinical factors. In addition, the association persisted when restricting analysis to patients with MSSA bacteraemia treated with flucloxacillin. This suggests that elevated vancomycin MIC is associated with but not causally linked to an organism factor that is responsible for increased mortality.     

Case fatality ratio and mortality rate trends of community-onset Staphylococcus aureus bacteraemia

Lethal outcomes can be expressed as a case fatality ratio (CFR) or as a mortality rate per 100 000 population per year (MR). Population surveillance for community-onset methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus bacteraemia was conducted in Canada, Australia, Sweden and Denmark to evaluate 30-day CFR and MR trends between 2000 and 2008. The CFR was 20.3% (MSSA 20.2%, MRSA 22.3%) and MR was 3.4 (MSSA 3.1, MRSA 0.3) per 100 000 per year. Although MSSA CFR was stable the MSSA MR increased; MRSA CFR decreased while its MR remained low during the study. Community-onset S. aureus bacteraemia, particularly MSSA, is associated with major disease burden. This study highlights complementary information provided by evaluating both CFR and MR.     

Biofilm production is not associated with poor clinical outcome in 485 patients with Staphylococcus aureus bacteraemia

ObjectivesStaphylococcus aureus biofilm may constitute a major cause of virulence. Our main objective was to analyse whether there was an association between biofilm production and poor outcome in patients with S. aureus bacteraemia.MethodsWe studied 485 S. aureus strains isolated from the blood of patients with bacteraemia from 2012 to 2015. We assessed in vitro biomass production using crystal violet assay and metabolic activity using tetrazolium salt assay. Strains were classified in tertile ranks as follows: low biomass producers, moderate biomass producers, high biomass producers, low metabolic activity, moderate metabolic activity and high metabolic activity. We excluded from analysis strains with moderate crystal violet and tetrazolium salt values. We defined poor outcome as fulfillment of one or more of the following conditions: 30-day attributable mortality, infective endocarditis, persistent bacteraemia and recurrent bacteraemia.ResultsOutcome was poor in 199 (41.0%) of 485 S. aureus bacteraemia episodes. The distribution of poor outcome with respect to biomass production and metabolic activity was as follows: low biomass producers, 36.6% vs. high biomass producers, 43.2% (p 0.26); and low metabolic activity, 43.5% vs. high metabolic activity, 36.2% (p 0.91). The presence of methicillin-resistant S. aureus was the only characteristic that was more likely to be present in the high metabolic activity group (17.4% vs. 39.3%, p < 0.001).ConclusionsBiofilm production, as determined by any of the methods used in the present study, is not associated with poor outcome in patients with S. aureus bacteraemia.     

What risk of endocarditis is low enough to justify the omission of transoesophageal echocardiography in Staphylococcus aureus bacteraemia? A narrative review

BackgroundRecent criteria which can identify patients with Staphylococcus aureus bacteraemia (SAB) who are at very low risk of endocarditis raise the question of whether transoesophageal echocardiography (TOE) is appropriate for these patients.AimsTo estimate the probability of occult endocarditis complicating SAB below which a TOE-guided treatment strategy no longer offers the best 180-day survival, and to examine the key uncertainties affecting this result.SourcesEstimates of the parameters required to calculate the Pauker–Kassirer testing threshold were identified from studies published prior to 1 June 2017 using a composite search strategy that involved a systematic search for relevant controlled trials and guidelines, followed by a non-systematic iterative search of the observational literature.ContentEstimates of the necessary parameters were generally consistent across the literature with the exception of the procedural mortality of TOE. In our base-case scenario (TOE mortality 0.1%), the testing threshold for TOE in apparently uncomplicated SAB was a 1.1% probability of occult endocarditis. Sensitivity analyses revealed that the procedural mortality of TOE was a key uncertainty affecting estimates of the testing threshold.ImplicationsNone of the available clinical tools can place patients with SAB below this probability of endocarditis with 95% confidence. Future work in this area should concentrate on improving the precision of these tools and on exploring the value of alternative echocardiography strategies. In addition, a better understanding of the harms of TOE is required to ensure that recommendations regarding the role of this investigation in the management of patients with SAB are appropriate.     

Are all beta-lactams similarly effective in the treatment of methicillin-sensitive Staphylococcus aureus bacteraemia?

Methicillin-sensitive Staphylococcus aureus (MSSA) is susceptible to many beta-lactams. We compared cloxacillin and cefazolin, the first-line recommended antibiotics, and other beta-lactams in the treatment of MSSA bacteraemia. This was a retrospective cohort study. Included were adult patients with clinically-significant MSSA bacteraemia treated with a beta-lactam that was started within 48 h after blood cultures were taken. We separated between empirical treatment administered to the patient before receipt of final blood culture results and definitive treatment administered thereafter. Univariate and multivariable analyses for 30-day (empirical treatment) and 90-day (definitive treatment) mortality were conducted, including the type of beta-lactam administered to the patient. Five-hundred and forty-one patients were included for the analysis of empirical treatment and 498 patients alive at 7 days were evaluable for definitive treatment. Empirical treatment with cloxacillin or cefazolin (n = 131) was associated with lower 30-day mortality as compared with cefuroxime (n = 98, p 0.058), ceftriaxone or cefotaxime (n = 194, p 0.008) and beta-lactam-beta-lactamase combinations (n = 61, p 0.013), with adjusted odds ratios (OR) for death ranging from 1.98 to 2.68. Definitive treatment with cefazolin (n = 72) was not significantly different from cloxacillin (n = 281); adjusted OR for 90-day mortality 0.91 (95% confidence interval 0.47–1.77). Treatment with cefazolin both in the empirical and definitive periods was not significantly different from cloxacillin; adjusted OR 0.81 (95% confidence interval 0.18–3.62). Treatment of MSSA bacteraemia with cefazolin is not significantly different from treatment with cloxacillin, while treatment with other beta-lactams, including second and third generation cephalosporins, might be associated with higher mortality.     

Why don't we have more inhaled antibiotics to treat ventilator-associated pneumonia?

BackgroundThe increasing prevalence of ventilator-associated pneumonia (VAP) due to either multidrug-resistant (MDR) organisms or infections with limited treatment options (i.e. susceptible to only aminoglycosides or colisitin) coupled with a dearth of new antimicrobials has led clinicians to pursue alternative management strategies including the use of inhaled antibiotics (IA).ObjectivesTo review the evidence surrounding the use of IA in the treatment of VAP with a focus on establishing a path whereby adjunctive IA could become a standard therapy for the treatment of specific VAP patient populations.SourcesA meta-analysis performed by the 2016 IDSA/ATS Hospital-acquired Pneumonia Guideline Committee; a PubMed and clinicaltrials.gov search for subsequent trials of IA for the treatment of VAP.ContentBased on a meta-analysis of nine studies (RR 1.29; 95% CI 1.13–1.47), the 2016 IDSA/ATS Hospital-acquired Pneumonia Guideline Committee recommended that adjunctive IA be used to treat VAP due to Gram-negative bacilli that are susceptible to only aminoglycosides or polymyxins. Two subsequent randomized trials of adjunctive IA for the treatment of mechanically ventilated patients with pneumonia failed to demonstrate a benefit. Despite these results, an updated meta-analysis (n = 11) including these two recent trials suggests a benefit of adjunctive IA for the treatment of VAP due to MDR and difficult-to-treat infections (RR 1.2; 95% CI 1.05–1.57).ImplicationsPatients with VAP and limited intravenous antibiotic options are the individuals most likely to benefit from adjunctive IA and should be the focus of future investigative studies. Although vibrating mesh nebulizers predominate in pharmaceutical company-sponsored trials, these devices have not been directly compared with the traditional jet nebulizers in terms of efficacy or safety.     

Prognostic impact of hyperglycemia at onset of methicillin-sensitive <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> bacteraemia

Previous reports have associated hyperglycemia to poor outcome among aged and comorbid Staphylococcus aureus bacteraemia (SAB) patients. However, the prognostic impact of hyperglycemia in SAB irrespective of age and underlying conditions including a diagnosis of diabetes has received little attention. The objective here was to evaluate the prognostic relevance of hyperglycemia at onset of methicillin-sensitive SAB (MS-SAB). It was a retrospective study of MS-SAB patients. Blood glucose was measured within 24 h of positive blood cultures. The patient cohort was analyzed en bloc and by categorization according to age, underlying conditions and a diagnosis of diabetes. Altogether 161 patients were identified. High initial blood glucose levels were observed among diabetics (p?<?0.001), patients with deep infections (p?<?0.05) and poor outcome at 28- or 90-days (p?<?0.05). Receiver operating characteristics presented the glucose cut-off level of 7.2 mmol/L as a significant predictor of mortality with an area under the curve of 0.63 (95% CI 0.52–0.75, p?<?0.05). Blood glucose ≥7.2 mmol/L connected to higher 28- (9 vs. 20%, p?<?0.05) and 90-day (14 vs. 29%, p?<?0.01) mortality. In Cox proportional hazard regression the blood glucose cut-off value of 7.2 mmol/L significantly predicted 90-day mortality (HR, 2.12; 95% CI, 1.01–4.46; p?<?0.05). Among young and healthy non-diabetics the negative prognostic impact of high glucose was further accentuated (HR 7.46, p?<?0.05). High glucose levels had no prognostic impact among diabetics. Hyperglycemia at SAB onset may associate to poor outcome. The negative prognostic impact is accentuated among young and healthy non-diabetics.     

Population pharmacokinetics of cefazolin in critically ill children infected with methicillin-sensitive Staphylococcus aureus

ObjectivesCefazolin is one of curative treatments for infections due to methicillin-sensitive Staphylococcus aureus (MSSA). Both growth and critical illness may impact the pharmacokinetic (PK) parameters. We aimed to build a population PK model for cefazolin in critically ill children in order to optimize individual dosing regimens.MethodsWe included all children (age < 18 years, body weight (BW) > 2.5 kg) receiving cefazolin for MSSA infection. Cefazolin total plasma concentrations were quantified by high-performance liquid chromatography. A data modelling process was performed with the software MONOLIX. Monte Carlo simulations were used in order to attain the PK target of 100% fT _{> 4 × MIC}.ResultsThirty-nine patients with a median (range) age of 7 (0.1–17) years and a BW of 21 (2.8–79) kg were included. The PK was ascribed to a one-compartment model, where typical clearance and volume of distribution estimations were 1.4 L/h and 3.3 L respectively. BW, according to the allometric rules, and estimated glomerular filtration rate (eGFR) on clearance were the two influential covariates. Continuous infusion with a dosing of 100 mg/kg/day to increase to 150 mg/kg/day for children with a BW < 10 kg or eGFR >200 mL/min/1.73m² were the best schemes to reach the PK target of 100% fT _{> 4 × MIC}.ConclusionsIn critically ill children infected with MSSA, continuous infusion seems to be the most appropriate scheme to reach the PK target of 100 % fT _{> 4 × MIC} in children with normal and augmented renal function.     

Comparison of Clinical Outcomes for Glycopeptides and Beta-Lactams in Methicillin-Susceptible Staphylococcus Aureus Bloodstream Infections

PurposeThis study aimed to provide compelling evidence of anti-staphylococcal beta-lactam use for methicillin-susceptible Staphylococcus aureus bloodstream infection (MSSA BSI).Materials and MethodsWe retrospectively collected data on patients with MSSA BSI who were admitted to two academic tertiary-care hospitals from 2010 to 2018. Only patients who received nafcillin, cefazolin, vancomycin, or teicoplanin as definitive therapy were included. The primary outcome was 28-day mortality. To perform unbiased comparisons between both treatments, we used inverse probability of treatment weighting (IPTW) analysis.ResultsA total of 359 patients were divided into two groups based on the definitive therapy used: beta-lactams (n=203), including nafcillin or cefazolin; and glycopeptides (n=156), including vancomycin or teicoplanin. In the IPTW analysis, glycopeptides were associated with significantly increased odds of 28-day mortality (adjusted odds ratio, 3.37; 95% confidence interval, 1.71–6.61; p<0.001). The rate of primary outcome in prespecified subgroups was largely consistent with the main analysis.ConclusionDefinitive therapy with beta-lactams in patients with MSSA BSI was associated with lower 28-day mortality compared to definitive therapy with glycopeptides.     

How I manage a patient with MRSA bacteraemia

BackgroundStaphylococcus aureus bloodstream infections are common and associated with a high mortality of 15–25%. Methicillin-resistant S. aureus (MRSA) bloodstream infection accounts for 10–40% of cases, and has an even higher mortality. Despite being the ‘bread and butter’ of clinical infectious diseases practice, robust evidence to guide optimal management is often lacking and there is wide variation in practice.ObjectivesTo provide a real-world example of a case of MRSA bacteraemia and the thought processes of the authors as key management decision points are reached.SourcesThe discussion is based on recent literature searches of relevant topics. In making recommendations, randomized clinical trial data have been prioritized and highlighted, and where these are not available recommendations are based on the experience and opinions of the authors.ContentFor a patient with MRSA bacteraemia and a primary bone and joint infection the following points are discussed: empirical antibiotic choice for suspected S. aureus bacteraemia; directed antibiotic choice for MRSA; monitoring and dosing of vancomycin; the role of combination therapy when bacteraemia is persistent; and the duration of therapy and role of switching to oral antibiotics.ImplicationsWhile broad principles of aggressive source control and appropriate choice and duration of antibiotics are important, the heterogeneity of S. aureus bacteraemia means that a tailored rather than algorithmic approach to management is often required. Further randomized controlled trials are needed to strengthen the evidence base for the management of MRSA bacteraemia.     

Close cooperation between infectious disease physicians and attending physicians can result in better management and outcome for patients with Staphylococcus aureus bacteraemia

Staphylococcus aureus bacteraemia (SAB) is a serious infection that demands prompt clinical attention for good outcome. To assess the impact of intervention by infectious diseases physicians (IDPs) in cases with SAB, a retrospective cohort study of patients with SAB was performed in a 1240-bed, university hospital in Japan, with the aim of comparing the management and outcome of patients during the initial and the latter half of the intervention period,. Three hundred and forty-six patients with SAB during the 7-year period, from 2002 to 2008, were included, and 194 patients in the initial half of the period (from 2002 to 2005) were compared with 152 patients in the later period (from 2006 to 2008). There was no significant difference between the two groups with respect to patient's clinical background, although more patients in the later period were receiving immunosuppressive treatment. The proportion of methicillin resistant S. aureus was lower during the later period (56.2% vs. 43.3%; p 0.02). Echocardiography was used more frequently (37.1% vs. 64.5%; p < 0.001). Infective endocarditis and metastatic infections were diagnosed more frequently (10.8% vs. 20.4%; p 0.01). Follow-up blood cultures were obtained more regularly (52.1% vs. 73.7%; p <0.001) and therapy was more frequently administered for at least 14 days (47.4% vs. 82.2%; p <0.001). The 30-day mortality improved during the intervention period (25.8% vs. 16.4%; p 0.04). The total number of blood cultures received by the laboratory increased annually and the total number of consultations increased by approximately 1.6-fold compared to 2002. Proactive intervention by IDPs raised awareness of optimal management of bacteraemia and improved the adherence to the standards of care, which subsequently resulted in an improvement in the outcome.     

Epidemiology and clinical presentation of community-acquired Staphylococcus aureus bacteraemia in children under 5 years of age admitted to the Manhiça District Hospital,Mozambique, 2001–2019

Staphylococcus aureus bacteraemia (SAB) is one of the most common bloodstream infections globally. Data on the burden and epidemiology of community-acquired SAB in low-income countries are scarce but needed to define preventive and management strategies. Blood samples were collected from children < 5 years of age with fever or severe disease admitted to the Manhiça District Hospital for bacterial isolation, including S. aureus. Between 2001 and 2019, 7.6% (3,197/41,891) of children had bacteraemia, of which 12.3% corresponded to SAB. The overall incidence of SAB was 56.1 episodes/100,000 children-years at risk (CYAR), being highest among neonates (589.8 episodes/100,000 CYAR). SAB declined significantly between 2001 and 2019 (322.1 to 12.5 episodes/100,000 CYAR). In-hospital mortality by SAB was 9.3% (31/332), and significantly associated with infections by multidrug-resistant (MDR) strains (14.7%, 11/75 vs. 6.9%, 14/204 among non-MDR, p = 0.043) and methicillin-resistant S. aureus (33.3%, 5/15 vs. 7.6%, 20/264 among methicillin-susceptible S. aureus, p = 0.006). Despite the declining rates of SAB, this disease remains an important cause of death among children admitted to MDH, possibly in relation to the resistance to the first line of empirical treatment in use in our setting, suggesting an urgent need to review current policy recommendations.

     

Should we reconsider cefazolin for treating staphylococcal meningitis? A retrospective analysis of cefazolin and cloxacillin cerebrospinal fluid levels in patients treated for staphylococcal meningitis

ObjectivesTo assess the meningeal penetration of cefazolin and cloxacillin in individuals treated for methicillin-susceptible staphylococcal meningitis.MethodsWe retrospectively identified individuals treated for Staphylococcus meningitis with measurements of cefazolin or cloxacillin concentrations in cerebrospinal fluid (CSF) using a validated assay of liquid chromatography coupled with mass spectrometry at the Nantes University Hospital between January 2009 and October 2019. Staphylococcus meningitis was defined by a compatible clinical presentation and a microbiological confirmation (positive CSF culture or positive specific PCR). Medical charts were retrospectively reviewed to collect microbiological and clinical data, and to assess therapeutic success.ResultsAmong the 17 included individuals, eight (47%) were treated with cefazolin and nine (53%) with cloxacillin. Median daily dosages of cefazolin and cloxacillin were 8 g (range 6–12 g) and 12 g (range 10–13 g), respectively. Cefazolin and cloxacillin were mainly administered by continuous infusion. Eleven individuals (65%) were men, median (interquartile range (IQR)) age was 54 years (50; 70), 14 (82%) had postoperative meningitis and 3 (18%) had haematogenous meningitis. Median (IQR) antibiotic CSF concentrations were 2.8 mg/L (2.1; 5.2) and 0.66 mg/L (0.5; 0.9) for cefazolin and cloxacillin groups, respectively. Cloxacillin was discontinued in two individuals for therapeutic failure.ConclusionsPatients with staphylococcal meningitis treated with high-dose continuous intravenous infusion of cefazolin achieved therapeutic concentrations in CSF. Cefazolin appears to be a therapeutic candidate that should be properly evaluated in this indication.     

Time to blood culture positivity in Staphylococcus aureus bacteraemia to determine risk of infective endocarditis

ObjectivesPatients with Staphylococcus aureus bacteraemia (SAB) at risk for infective endocarditis (IE) need to be identified because they should undergo echocardiography. We validated previous scoring systems for IE risk determination and evaluated whether time to blood culture positivity (TTP) could improve scoring systems.MethodsThis retrospective population-based study included adults with SAB in 2016 in a derivation cohort and those from 2017 in a validation cohort. TTP was compared between patients with and without IE. A new score including TTP was constructed using a least absolute shrinkage selection operator. The new POSITIVE score was compared to the previously described PREDICT and VIRSTA scores.ResultsA total of 465 episodes with SAB were included in the derivation cohort, of which 38 (8.2%) represented IE. Median (interquartile range) TTP was significantly shorter in episodes with IE, at 8.7 (7.7–10.6) hours compared to those without, at 13.3 (10.5–16.5) hours. When using a cutoff at 13 hours, TTP had a sensitivity of 100% (95% confidence interval (CI), 91–100) and specificity of 52% (95% CI, 47–57) for IE. The POSITIVE score included TTP, intravenous drug use, embolizations and presence of preexisting heart conditions. It had a sensitivity of 93% (95% CI, 76–99) and a specificity of 70% (95% CI, 66–74) in the validation cohort. The performance of POSITIVE was superior to PREDICT, and the specificity was higher than that of VIRSTA.ConclusionsTTP, either by itself or as part of the POSITIVE score, can be used to identify patients with SAB at low risk for IE. Further validation is needed because TTP is sensitive to several external factors.