Reduced wound leakage in arthroplasty with modified wound closure: a retrospective cohort study.

INTRODUCTION: Wound leakage has been shown to increase the risk of prosthetic joint infections (PJIs) in primary total hip (THA) and knee arthroplasty (unicondylar and total knee arthroplasty; KA). The aim of this study is to determine whether the addition of a continuous subcuticular bonding stitch to a conventional three-layer closure method reduces the incidence of prolonged wound leakage and PJIs after THA and KA. MATERIALS AND METHODS: This retrospective cohort study included all patients receiving a THA or KA. Patients in the control group with a three-layer closure method had surgery between November 1st 2015 and October 31st 2016, and were compared to the study group with a four-layer closure method that had surgery between January 1st 2017 and December 31st 2018. The primary outcome was incidence of prolonged wound leakage longer than 72 h. Differences were evaluated using logistic regression. Incidence of PJIs was the secondary outcome. RESULTS: A total of 439 THA and 339 KA in the control group and 460 THA and 350 KA in the study group were included. In the control group, 11.7% of the patients had a prolonged leaking wound compared to 1.9% in the study group (p < 0.001). The modified wound closure method showed a protective effect for obtaining prolonged wound leakage; odds ratios were 0.09 (95% CI 0.04-0.22; p < 0.001) for THA and 0.21 (95% CI 0.10-0.43; p < 0.001) for KA. PJIs decreased from 1.54 to 0.37% (p = 0.019). CONCLUSIONS: The addition of a continuous subcuticular bonding stitch reduces the incidence of prolonged wound leakage and PJIs after THA and KA compared to a conventional three-layer wound closure method. The large reduction of incidence in wound leakage and PJIs in this study, combined with relatively negligible cost and effort of the modified wound closure method, would advocate for implementing this wound closure method in arthroplasty.

Bilateral periprosthetic joint infection with Ureaplasma urealyticum in an immunocompromised patient.

This case study discusses how we diagnosed and treated a patient with a late haematogenous bilateral periprosthetic joint infection (PJI) after total knee arthroplasties caused by Ureaplasma urealyticum. This has never been reported before. We will discuss how we used a PET-CT, synovial fluid cell count, and synovial fluid analysis by 16S rRNA gene sequencing to diagnose this PJI. We will also discuss how we treated this patient to obtain full recovery.

Time-course of antibody responses against Coxiella burnetii following acute Q fever.

Large outbreaks of Q fever in The Netherlands have provided a unique opportunity for studying longitudinal serum antibody responses in patients. Results are presented of a cohort of 344 patients with acute symptoms of Q fever with three or more serum samples per patient. In all these serum samples IgM and IgG against phase 1 and 2 Coxiella burnetii were measured by an immunofluorescence assay. A mathematical model of the dynamic interaction of serum antibodies and pathogens was used in a mixed model framework to quantitatively analyse responses to C. burnetii infection. Responses show strong heterogeneity, with individual serum antibody responses widely different in magnitude and shape. Features of the response, peak titre and decay rate, are used to characterize the diversity of the observed responses. Binary mixture analysis of IgG peak levels (phases 1 and 2) reveals a class of patients with high IgG peak titres that decay slowly and may represent potential chronic cases. When combining the results of mixture analysis into an odds score, it is concluded that not only high IgG phase 1 may be predictive for chronic Q fever, but also that high IgG phase 2 may aid in detecting such putative chronic cases.

Routine screening for Coxiella burnetii infection during pregnancy: a clustered randomised controlled trial during an outbreak, the Netherlands, 2010.

Between 2007 and 2010, the Netherlands experienced one of the largest outbreaks of Q fever. Since asymptomatic Coxiella burnetii infection has been associated with maternal and obstetric complications, evidence about the effectiveness of routine screening during pregnancy in outbreak areas is needed. We performed a clustered randomised controlled trial during the Dutch outbreak, in which 55 midwife centres were randomised to recruit pregnant women for an intervention or control strategy. In both groups a serum sample was taken between 20 and 32 weeks of gestation. In the intervention group (n=536), the samples were analysed immediately by indirect immunofluorescence assay for the presence of IgM and IgG (phase I/II) and treatment was given during pregnancy in case of an acute or chronic infection. In the control group (n=693), sera were frozen for analysis after delivery. In both groups 15% were seropositive. In the intervention group 2.2% of the women were seropositive and had an obstetric complication, compared with 1.4% in the control group (Odds ratio: 1.54 (95% confidence interval 0.60-3.96)). During a large Q fever outbreak, routine C. burnetii screening starting at 20 weeks of gestation was not associated with a relevant reduction in obstetric complications and should therefore not be recommended.

Comparison of ELISA and indirect immunofluorescent antibody assay detecting Coxiella burnetii IgM phase II for the diagnosis of acute Q fever.

A commercially available enzyme-linked immunosorbent assay (ELISA) detecting Coxiella burnetii phase II-specific IgM for the diagnosis of acute Q fever was compared with indirect immunofluorescent antibody assay (IFA). IFA is the current reference method for the detection of antibodies against C. burnetii, but has disadvantages because the judgment of fluorescence is subjective and tiring, and the test is expensive and automation is not possible. To examine whether phase II IgM ELISA could be used as a screening assay for acute Q fever, we compared the sensitivity and specificity of IFA and ELISA. The sensitivity of the IFA and ELISA tests were 100 and 85.7%, respectively, with a specificity of 95.3 and 97.6%, respectively. Because of the high sensitivity and specificity of the ELISA in combination with the practical disadvantages of the IFA, we introduced a new algorithm to screen samples of patients with symptoms of acute Q fever infection.

Solitary IgM phase II response has a limited predictive value in the diagnosis of acute Q fever.

We investigated the positive predictive value (PPV) of a solitary positive immunoglobulin M (IgM) phase II response for the serodiagnosis of acute Q fever detected with either an indirect immunofluorescence assay (IFA) or an enzyme-linked immunosorbent assay (ELISA). Initial and follow-up sera from patients suspected of acute Q fever were included if initially only IgM phase II tested positive with IFA in 2008 (n=92), or ELISA in 2009 (n=85). A seroconversion for Q fever was defined as an initial sample being IgG phase II negative but positive in the follow-up sample. The PPV of an initial isolated IgM phase II result detected by IFA or ELISA was 65% and 51%, respectively, and therefore appeared not to adequately predict acute Q fever. For this reason it cannot be used as a diagnostic criterion nor should it be included in public health notification without confirmation with other markers or a follow-up serum sample.

Screening for Coxiella burnetii infection during pregnancy: pros and cons according to the Wilson and Jungner criteria.

In Europe the incidence of human Q fever has dramatically increased over the previous years. Untreated infections with Coxiella burnetii, the causal agent of Q fever, have been associated with both obstetric and maternal complications. The majority of pregnant women with a C. burnetii infection remain asymptomatic, hence screening could be of value to prevent unwanted outcomes in this high-risk group. We applied the updated Wilson and Jungner criteria to review the evidence for routine screening for C. burnetii infection during pregnancy. Since much uncertainty remains about the incidence, clinical consequences, diagnostics and treatment of C. burnetii infection during pregnancy, routine screening for C. burnetii infection during pregnancy should not be recommended. Rigorous studies to assess the effectiveness of C. burnetii screening are warranted.

Validation and implementation of the Panbio COVID-19 Ag rapid test for the diagnosis of SARS-CoV-2 infection in symptomatic hospital healthcare workers.

BACKGROUND: RT-PCR is the current recommended laboratory method to diagnose SARS-CoV-2 in healthcare workers (HCW). As RT-PCR is not widely available and is time-consuming, it limits decision making on removal from and return to work of possibly contagious HCW. AIM: In this study we evaluated the Panbio™ COVID-19 Ag rapid test (PanbioCAgRT) in 825 hospital HCW. METHODS AND FINDING: This study consisted of two phases. In the validation phase, we tested hospital HCW with mild symptoms (three days or less) in parallel using the PanbioCAgRT and the RT-qPCR test. The PanbioCAgRT demonstrated 86.7% sensitivity, 100% specificity, 100% PPV and 98.5% NPV with regard to RT-qPCR. For HCW with PanbioCAgRT-/RT-qPCR+, the median Ct value was 30.9, whereas for the HCW with PanbioCAgRT+/RT-qPCR+ the median Ct value was 19.3 (P<0.001). In the second phase, we implemented an on-site antigen test-based strategy for symptomatic hospital HCW: HCW that tested positive with the PanbioCAgRT on-site were considered SARS-CoV-2 positive and were sent home. HCW that tested negative with the PanbioCAgRT on-site were allowed to work with PPE pending RT-qPCR test results from the laboratory. Sensitivity of the antigen test-based strategy was 72.5% and NPV was 97%. For HCW with PanbioCAgRT-/RT-qPCR+ median Ct values were 27.8. CONCLUSION: The PanbioCAgRTt validated in this study showed a high sensitivity and specificity in samples obtained from HCW with high viral loads. The antigen-based testing strategy proposed in this study seems to be effective, safe and easy to implement in a wide range of occupational healthcare settings.

MRSA carriage in healthcare personnel in contact with farm animals.

In The Netherlands it has been shown that people in contact with pigs have a higher risk of meticillin-resistant Staphylococcus aureus (MRSA) carriage than the general population. Isolates of closely related spa types, corresponding to multilocus sequence type (MLST) ST398, were found in pig farmers, pig veterinarians and pigs. The objective of this study was to investigate whether contact with pigs and veal calves or other livestock is a risk factor for MRSA carriage in Dutch healthcare workers (HCWs). HCWs at four general hospitals and one university hospital were asked to fill in questionnaires covering contact with animals and to take MRSA cultures of their throat and nares. Cultures of HCWs in contact with livestock were processed with samples from HCWs with no contact with livestock as controls. Seventy-seven of 1721 HCWs (4.4%) reported direct or indirect contact with pigs and/or veal calves and 145 reported contact with other livestock animals. The MRSA carriage rate in the group in contact with pigs and veal calves was 1.7% and in the control group was 0.15%. No carriers were found among HCWs in contact with other livestock. An estimated 3% of hospital staff working in Dutch hospitals serving rural populations belong to a high risk group for MRSA carriage according to the Dutch guidelines. Although MRSA carriage in HCWs in contact with livestock is 10-fold higher than in other HCWs, the difference is not statistically significant.

[Clindamycin is unsuitable for the empirical treatment of infections due to pig-related methicillin-resistant Staphylococcus aureus (MRSA)]. / Clindamycine niet geschikt voor empirische behandeling van infecties veroorzaakt door meticillineresistente Staphylococcus aureus (MRSA) afkomstig van varkens.

OBJECTIVE: To determine the antibiotic sensitivity of methicillin-resistant Staphylococcus aureus (MRSA) isolated from persons in contact with pigs. DESIGN: Retrospective. METHOD: The pig-related MRSA collection, built up between January 1st 2003 and November 30th 2006 in the Regional Laboratory for Medical Microbiology and Infection Prevention (RLMMI) of the Jeroen Bosch Hospital, Den Bosch, The Netherlands, was tested for sensitivity to a large number ofantibiotics. RESULTS: A total of 65 isolates were obtained from 53 patients. All (100%) of the pig-related MRSA isolates were sensitive to vancomycin, teicoplanin, nitrofurantoin, rifampicin, linezolid, and quinupristin-dalfopristin. Variable sensitivity was found for erythromycin (40%), clindamycin (48%), cotrimoxazole (48%), aminoglycosides (92%), tetracycline (6%), and quinolones (94%). CONCLUSION: In view of the sensitivities found, clindamycin does not seem suitable for the empirical therapy ofpig-related MRSA-infections. In case of severe infection, therapy should be started either with an intravenous glycopeptide or with oral ciprofloxacin, possibly combined with rifampicin or linezolid.

Molecular epidemiology of hepatitis A in Noord-Brabant, The Netherlands.

BACKGROUND: Previous studies on the molecular epidemiology of hepatitis A virus (HAV) in Amsterdam, The Netherlands, show that subgenotype 1A is mainly seen among homosexual men practising anonymous oral-anal sex in saunas and darkrooms, while subgenotype 1B is usually detected among children originating from Morocco, and subgenotype 3A is mostly found among travellers to Pakistan. OBJECTIVE: We studied the genotype distribution in a more rural area of The Netherlands, Noord-Brabant, and compared it with Amsterdam. STUDY DESIGN: We collected blood and feces samples from 34 HAV IgM(+) individuals who were reported from August 2001-March 2003 at the Municipal Health Service (MHS) Heart for Brabant (Brabant). We also collected feces samples from nine household contacts of whom the HAV IgM status was not known. HAV RNA was isolated and subsequently amplified by reverse transcriptase polymerase chain reaction (RT-PCR) at the VP1-P2a and the VP3-VP1 region, sequenced and analysed. RESULTS AND CONCLUSIONS: In most cases, relations between risk groups and HAV subgenotypes in Noord-Brabant were similar to those in Amsterdam. Next to genotypes 1 and 3 we also detected a genotype 2/7 strain in a Noord-Brabant case. Also, in contrast to the Amsterdam study, sporadic transmission occurred among various risk groups. Children involved in a school-related outbreak were infected with strains identical to one that was previously isolated from a man who has sex with men (MSM). Also, Dutch patients having no epidemiological link with Turkish or Moroccan children harboured strains imported from high-endemic countries. Furthermore, we report a special case in which HAV may be causally involved in meningitis. The results of this study show that the molecular epidemiology of HAV in The Netherlands can be more complicated than previously anticipated and that HAV phylogenetic studies can provide important information for the design of appropriate public health measures.

The use of lipid formulations of amphotericin B for systemic fungal infections.

Despite its considerable toxicity, amphotericin B (AmB) remains the 'golden standard' in the treatment of many systemic fungal infections. To reduce this toxicity, with the aim of increasing its therapeutic index, AmB can be encapsulated into liposomes or bound to lipid carriers. Following promising clinical results with investigational formulations, three industrial compounds are available at this moment: Abelcet (Amphotericin B Lipid Complex, ABLC), Amphocil (Amphotericin B Colloidal Dispersion) and AmBisome. These three formulations differ significantly in composition and pharmacokinetics. All three compounds share a considerable reduction of nephrotoxicity, but the number of acute reactions differ among these compounds, Amphocil showing the highest and AmBisome the lowest rate. Increased therapeutic indexes for all three formulations were shown only in some of the animal models for several fungal infections. Four recent clinical trials comparing these formulations with AmB demonstrated their clinical efficacy but failed to clearly show an increased therapeutic index. Therefore these compounds can be recommended in cases of intolerance to or failure on AmB therapy. The optimal therapeutic dosages have not been established, but dosages as low as 1 mg/kg should probably be avoided in the initial treatment of fulminant fungal infections, since efficacy may be inferior to equal dosages of conventional AmB.

Liposomal amphotericin B (AmBisome) compared with amphotericin B both followed by oral fluconazole in the treatment of AIDS-associated cryptococcal meningitis.

OBJECTIVE: Amphotericin B deoxycholate initial therapy and fluconazole maintenance therapy is the treatment of choice for AIDS-associated cryptococcal meningitis. However, the administration of amphotericin B is associated with considerable toxicity. A potential strategy for reducing the toxicity and increasing the therapeutic index of amphotericin B is the use of lipid formulations of this drug. DESIGN AND METHODS: HIV-infected patients with cryptococcal meningitis were randomized to treatment with either liposomal amphotericin B (AmBisome) 4 mg/kg daily or standard amphotericin B 0.7 mg/kg daily for 3 weeks, each followed by fluconazole 400 mg daily for 7 weeks. During the first 3 weeks, clinical efficacy was assessed daily. Mycological response was primarily evaluated by cerebrospinal fluid (CSF) cultures at days 7, 14, 21 and 70. RESULTS: Of the 28 evaluable patients, 15 were assigned to receive AmBisome and 13 to receive amphotericin B. Baseline characteristics were comparable. The time to and the rate of clinical response were the same in both arms. AmBisome therapy resulted in a CSF culture conversion within 7 days in six out of 15 patients versus one out of 12 amphotericin B-treated patients (P = 0.09), within 14 days in 10 out of 15 AmBisome patients versus one out of nine amphotericin B patients (P = 0.01), and within 21 days in 11 out of 15 AmBisome patients versus three out of eight amphotericin B patients (P = 0.19). When Kaplan-Meier estimates were used to compare time to CSF culture conversion, AmBisome was more effective (P < 0.05; median time between 7 and 14 days for AmBisome versus > 21 days for amphotericin B). AmBisome was significantly less nephrotoxic. CONCLUSIONS: A 3-week course of 4 mg/kg AmBisome resulted in a significantly earlier CSF culture conversion than 0.7 mg/kg amphotericin B, had equal clinical efficacy and was significantly less nephrotoxic when used for the treatment of primary episodes of AIDS-associated cryptococcal meningitis.

Placental histopathology after Coxiella burnetii infection during pregnancy.

Symptomatic and asymptomatic Coxiella burnetii infection during pregnancy have been associated with obstetric complications. We described placental histopathology and clinical outcome of five cases with asymptomatic C. burnetii infection during pregnancy and compared these cases with four symptomatic cases from the literature. In contrast with the symptomatic cases, we did not observe necrosis or active inflammation in the placentas of the asymptomatic women. Obstetrical outcome was more favourable in the asymptomatic cases than in the symptomatic cases. Asymptomatic and symptomatic C. burnetii infection during pregnancy are different entities with respect to placental histopathology and the risk of obstetric complications.

Early diagnosis and treatment of patients with symptomatic acute Q fever do not prohibit IgG antibody responses to Coxiella burnetii.

Little is known about the effect of timing of antibiotic treatment on development of IgG antibodies following acute Q fever. We studied IgG antibody responses in symptomatic patients diagnosed either before or during development of the serologic response to Coxiella burnetii. Between 15 and 31 May 2009, 186 patients presented with acute Q fever, of which 181 were included in this retrospective study: 91 early-diagnosed (ED) acute Q fever patients, defined as negative IgM phase II enzyme-linked immunosorbent assay (ELISA) and positive PCR, and 90 late-diagnosed (LD) acute Q fever patients, defined as positive/dubious IgM phase II ELISA and positive immunofluorescence assay (IFA). Follow-up serology at 3, 6, and 12 months was performed using IFA (IgG phase I and II). High IgG antibody titers were defined as IgG phase II titers of ≥1:1,024 together with IgG phase I titers of ≥1:256. At 12 months, 28.6% of ED patients and 19.5% of LD patients had high IgG antibody titers (P = 0.17). No statistically significant differences were found in frequencies of IgG phase I and IgG phase II antibody titers at all follow-up appointments for adequately and inadequately treated patients overall, as well as for ED and LD patients analyzed separately. Additionally, no significant difference was found in frequencies of high antibody titers and between early (treatment started within 7 days after seeking medical attention) and late timing of treatment. This study indicates that early diagnosis and antibiotic treatment of acute Q fever do not prohibit development of the IgG antibody response.