Decrease of hospital- and community-acquired bloodstream infections due to Streptococcus pneumoniae and Streptococcus pyogenes during the first year of the COVID-19 pandemic: A time-series analysis in Paris region.

The impact of the COVID-19 pandemic on bloodstream infections (BSIs) due to Streptococcus pneumoniae and Streptococcus pyogenes was assessed in 25 university hospitals of Paris. Monthly BSIs incidence rates that appeared stable in 2018 and 2019, decreased for the 2 pathogens during the 2 COVID-19 lockdown periods of 2020. Containment policies, including social distancing, masking and hand hygiene strengthening in both community and hospital settings are likely to reduce BSIs due to these pathogens.

Detection of SARS-CoV-2 in Saliva and Nasopharyngeal Swabs According to Viral Variants.

The genome of the Omicron variant of concern (VOC) contains more than 50 mutations, many of which have been associated with increased transmissibility, differing disease severity, and the potential to elute immune responses acquired after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination or infection with previous VOCs. Due to a better tropism for the upper respiratory tract, it was suggested that the detection of the Omicron variant could be preferred in saliva, compared to nasopharyngeal swabs (NPS). Our objective was to compare the SARS-CoV-2 levels in saliva fluid and NPS to estimated Ct values, according to the main SARS-CoV-2 variants circulating in France since the beginning of 2021. We analyzed 1,289 positive reverse transcription-polymerase chain reaction (RT-PCR) results during the three major waves: Alpha, Delta, and Omicron. NPS and saliva sampling were performed for 909 (71%) and 380 (29%) cases, respectively. The Ct values were significantly lower in the NPS samples than in the saliva samples for the three main VOCs. Still, the difference was less pronounced with the Omicron variant than for the Alpha and Delta variants. In contrast, in the saliva samples, Ct values were significantly lower for the Omicron variant than for the Delta (difference of -2.7 Ct) and the Alpha (difference of -3.0 Ct) variants, confirming a higher viral load in saliva. To conclude, the higher viral load in saliva was evidenced for the Omicron variant, compared to the Alpha and Delta variants, suggesting that established diagnostic methods might require revalidation with the emergence of novel variants. IMPORTANCE Established methods for SARS-CoV-2 diagnostics might require revalidation with the emergence of novel variants. This is important for screening strategy programs and for the investigation of the characteristics of new variants in terms of tropism modification and increased viral burden leading to its spread. SARS-CoV-2 RT-PCR screening on saliva samples reported lower but acceptable performance, compared to nasopharyngeal samples. Due to a better tropism for the upper respiratory tract, it was suggested that the detection of the Omicron variant could be preferred in saliva, compared to nasopharyngeal swabs. Our study analyzed 1,289 positive RT-PCR results during the three major waves in France: Alpha, Delta, and Omicron. Our findings also showed a higher viral load in saliva for the Omicron variant, compared to the Alpha and Delta variants.

Surging bloodstream infections and antimicrobial resistance during the first wave of COVID-19: a study in a large multihospital institution in the Paris region.

OBJECTIVES: This study measured the impact of the first wave of COVID-19 pandemic (COVID-19) (March-April 2020) on the incidence of bloodstream infections (BSIs) at Assistance Publique - Hôpitaux de Paris (APHP), the largest multisite public healthcare institution in France. METHODS: The number of patient admission blood cultures (BCs) collected, number of positive BCs, and antibiotic resistance and consumption were analysed retrospectively for the first quarter of 2020, and also for the first quarter of 2019 for comparison, in 25 APHP hospitals (ca. 14 000 beds). RESULTS: Up to a fourth of patients admitted in March-April 2020 in these hospitals had COVID-19. The BSI rate per 100 admissions increased overall by 24% in March 2020 and 115% in April 2020, and separately for the major pathogens (Escherichia coli, Klebsiella pneumoniae, enterococci, Staphylococcus aureus, Pseudomonas aeruginosa, yeasts). A sharp increase in the rate of BSIs caused by microorganisms resistant to third-generation cephalosporins (3GC) was also observed in March-April 2020, particularly in K. pneumoniae, enterobacterial species naturally producing inducible AmpC (Enterobacter cloacae...), and P. aeruginosa. A concomitant increase in 3GC consumption occurred. CONCLUSIONS: The COVID-19 pandemic had a strong impact on hospital management and also unfavourable effects on severe infections, antimicrobial resistance, and laboratory work diagnostics.

Outbreak of NDM-1-producing Klebsiella pneumoniae in the intensive care unit during the COVID-19 pandemic: Another nightmare.

An outbreak of Klebsiella pneumoniae producing the carbapenemase NDM-1 occurred in our ICU during the last COVID-19 wave. Twelve patients were tested positive, seven remained asymptomatic whereas 5 developed an infection. Resistome and in silico multilocus sequence typing confirmed the clonal origin of the strains. The identification of a possible environmental reservoir suggested that difficulties in observing optimal bio-cleaning procedures due to workload and exhaustion contributed to the outbreak besides the inappropriate excessive glove use.

Impact of systematic screening for AmpC-hyperproducing Enterobacterales intestinal carriage in intensive care unit patients.

BACKGROUND: Empirical antimicrobial therapy (EAT) is a challenge for community-acquired, hospital-acquired and ventilator-associated pneumonia, particularly in the context of the increasing occurrence of third-generation cephalosporin-resistant Enterobacterales (3GCR-E), including extended-spectrum beta-lactamase Enterobacterales (ESBL-E) and high-level expressed AmpC cephalosporinase-producing Enterobacterales (HLAC-E). To prevent the overuse of broad-spectrum antimicrobial therapies, such as carbapenems, we assessed the performance of screening for intestinal carriage of HLAC-E in addition to ESBL-E to predict 3GCR-E (ESBL-E and/or HLAC-E) presence or absence in respiratory samples in ICU, and to evaluate its potential impact on carbapenem prescription. MATERIALS AND METHODS: This monocentric retrospective observational study was performed in a surgical ICU during a 4-year period (January 2013-December 2016). Patients were included if they had a positive culture on a respiratory sample and a previous intestinal carriage screening performed by rectal swabbing within 21 days. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and likelihood ratios were calculated for the screening for intestinal carriage of ESBL-E, HLAC-E and 3GCR-E (ESBL-E and/or HLAC-E) as predictor of their absence/presence in respiratory samples. Impact of HLAC-E and ESBL-E reporting on EAT was also studied. RESULTS: 765 respiratory samples, retrieved from 468 patients, were analyzed. ESBL-E prevalence was 23.8% in rectal swab and 4.4% in respiratory samples. HLAC-E prevalence was 9.0% in rectal swabs and 3.7% in respiratory samples. Overall, the 3GCR-E prevalence was 31.8% in rectal swabs and 7.7% in respiratory samples. NPVs were 98.8%, 98.0% and 96.6% for ESBL-E, HLAC-E and 3GCR-E, respectively. Over the study period, empirical antimicrobial therapy was initiated for 315 episodes of respiratory infections: 228/315 (72.4%) were associated with negative intestinal carriage screening for both HLAC-E and ESBL-E, of whom 28/228 (12.3%) were treated with carbapenems. Of 23/315 (7.3%) cases with screening for positive intestinal carriage with HLAC-E alone, 10/23 (43.5%) were treated with carbapenems. CONCLUSION: Systematic screening and reporting of HLAC-E in addition to ESBL-E in intestinal carriage screening could help to predict the absence of 3GCR-E in respiratory samples of severe surgical ICU patients. This could improve the appropriateness of EAT in ICU patients with HAP and may prevent the overuse of carbapenems.

Impact of a 24/7 Rapid Molecular Assay for Influenza Detection on the Prescription of Oseltamivir.

We assessed the impact of a rapid molecular assay for influenza detection whether outsourced or performed onsite 24/7 in a University Hospital in Paris, France. Shorter median time-to-results (16.8 vs 2.3 hours, P < .05) and an increased rate of adequate prescription of oseltamivir (76.6% vs 95.3%, P < .05) were observed.

Benefits of Polymerase Chain Reaction Combined With Culture for the Diagnosis of Bone and Joint Infections: A Prospective Test Performance Study.

BACKGROUND: The microbiological diagnosis of bone and joint infections (BJI) currently relies on cultures, and the relevance of molecular methods is still debated. The aim of this study was to determine whether polymerase chain reaction (PCR) could improve the etiological diagnosis of BJI. METHODS: A prospective study was conducted during a 4-year period at Lariboisiere University Hospital (Paris, France), including patients with suspicion of infectious spondylodiscitis, septic arthritis, prosthetic joint infections, and respective noninfected groups. Clinical and radiological data were collected at inclusion and during follow-up. All samples were analyzed by conventional cultures and 16S ribosomal deoxyribonucleic acid (rDNA) gene (16S-PCR). Specific cultures and PCR targeting Mycobacterium tuberculosis were also performed for spondylodiscitis samples. Case records were subsequently analyzed by an independent expert committee to confirm or invalidate the suspicion of infection and definitively classify the patients in a case or control group. The sensitivity of the combination of culture and PCR was compared with culture alone. RESULTS: After expert committee analysis, 105 cases of BJI cases and 111 control patients were analyzed. The most common pathogens of BJI were staphylococci (30%), M tuberculosis (19%), and streptococci (14%). Adding PCR enhanced the sensitivity compared with culture alone (1) for the diagnosis of M tuberculosis spondylodiscitis (64.4% vs 42.2%; P < .01) and (2) for nonstaphylococci BJI (81.6% vs 71.3%; P < .01). It is interesting to note that 16S-PCR could detect BJI due to uncommon bacteria such as Mycoplasma and fastidious bacteria. CONCLUSIONS: Our study showed the benefit of 16S-PCR and PCR targeting M tuberculosis as add-on tests in cases of suspected BJI.

Relation between presence of extended-spectrum ß-lactamase-producing Enterobacteriaceae in systematic rectal swabs and respiratory tract specimens in ICU patients.

BACKGROUND: The choice of empirical antimicrobial therapy for pneumonia in intensive care unit (ICU) is a challenge, since pneumonia is often related to multidrug-resistant pathogens, particularly extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E). To prevent the overuse of broad-spectrum antimicrobial therapy, the main objective of this study was to test the performance of digestive colonization surveillance as a predictor of ESBL-E presence or absence in respiratory samples performed in ICU and to evaluate the impact of time sampling (≤5 days or >5 days) on such prediction. DESIGN: Multicentric retrospective observational study, including every patient with a respiratory tract specimen positive culture and a previous rectal ESBL-E screening performed within 7 days before the respiratory sample, between January 2012 and December 2014. Results were analyzed in two groups: respiratory samples obtained during the first 5 days of ICU stay (early group) and respiratory samples obtained after 5 days (late group). INTERVENTIONS: none. RESULTS: Among 2498 respiratory tract samples analyzed corresponding to 1503 patients, 1557 (62.3%) were performed early (≤5 days) and 941 (37.7%) later (>5 days). Positivity rates for ESBL-E were 15.0 and 36.8% for rectal swabs in the early and late groups, respectively. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and likelihood ratios were calculated for ESBL-E digestive colonization as a predictor of ESBL-E presence in respiratory samples. PPVs of ESBL-E digestive colonization were 14.5% (95% CI [12.8; 16.3]) and 34.4% (95% CI [31.4; 37.4]), for the early and late groups, respectively, whereas NPVs were 99.2% (95% CI [98.7; 99.6]) and 93.4% (95% CI [91.9; 95.0]), respectively. CONCLUSIONS: Systematic surveillance of ESBL-E digestive colonization may be useful to limit the use of carbapenems when pneumonia is suspected in ICU. When rectal swabs are negative, the risk of having ESBL-E in respiratory samples is very low even after 5 days of ICU stay.

Ceftriaxone-Resistant Neisseria gonorrhoeae Isolates (2010 to 2014) in France Characterized by Using Whole-Genome Sequencing.

Two extended-spectrum cephalosporin-resistant Neisseria gonorrhoeae isolates were discovered among 6,340 (0.03%) French isolates between 2010 and 2014. One isolate corresponded to the F89 multidrug-resistant N. gonorrhoeae isolate harboring a penA mosaic; whole-genome sequencing highlighted an additional R251H substitution in the ftsX gene recently involved in cephalosporin resistance. The other, ceftriaxone-resistant isolate (MIC, 0.25 mg/liter) harbored the PBP2 pattern XXXVI plus a P551S substitution and belonged to sequence type ST1579 (multilocus sequence typing [MLST]).

Standardized interpretation of antibiotic susceptibility testing and resistance genotyping for Mycobacterium abscessus with regard to subspecies and erm41 sequevar.

OBJECTIVES: The objective of this study was to provide standardized antibiotic susceptibility testing (AST) for Mycobacterium abscessus with regard to subspecies. METHODS: One hundred and sixty-five clinical isolates were tested for susceptibility to 15 antibiotics using a commercial microdilution method, at two reading times: (i) early reading time (ERT), when the growth control was first positive; and (ii) late reading time (LRT), of 14 days, for detecting inducible resistance. In addition, genes or mutations involved in resistance were studied [erm(41), rrl and rrs]. RESULTS: Three patterns were observed for clarithromycin: (i) MIC >16 mg/L at ERT (median 5 days) for 15 isolates [10 subsp. abscessus erm(41) sequevar T28, 3 subsp. bolletii and 2 subsp. massiliense] among which 9 harboured an a2058g/c rrl mutation; (ii) MIC ≤16 mg/L at ERT, but >16 mg/L at LRT, for 106 isolates [84 abscessus erm(41) T28 and 22 bolletii] showing intrinsic inducible resistance; and (iii) MIC ≤4 mg/L at ERT and LRT for 44 isolates [18 abscessus erm(41) C28 and 26 massiliense]. Amikacin MIC was >64 mg/L for eight isolates [five abscessus erm(41) T28, two massiliense and one bolletii] among which seven harboured the a1408g rrs mutation, but ≤64 mg/L for the remaining isolates without mutation. For the other antibiotics, only one WT pattern was observed, with cefoxitin, tigecycline and linezolid showing MIC values compatible with susceptibility. CONCLUSIONS: Standard AST can predict clarithromycin and amikacin resistance using interpretation rules with regard to subspecies. For other antibiotics, since only one pattern is observed, there is no need for systematic phenotypic or genotypic testing.

Short article: Hepatitis B virus status in children born to HIV/HBV coinfected women in a French hospital: a cross-sectional study.

OBJECTIVES: We assessed hepatitis B virus (HBV) status in children born to HIV/HBV coinfected women with large access to antiretroviral therapy. METHODS: All HIV/HBV coinfected pregnant women from 01 January 2000 to 01 January 2012 were included in the retrospective study (NCT02044068). Antiretroviral therapy during pregnancy and injection of HBV immunoglobulin/vaccine to newborns was recorded. We assessed HBV status of children aged at least 2 years. RESULTS: Twenty-one women (35 children) were studied. Twenty-six children (74%) had HBsAb: 22 had received immunoglobulin and 24 had received a complete vaccine (with immunoglobulin in 21 cases); their mothers had been administered lamivudine or tenofovir/emtricitabine during eight and nine pregnancies, respectively. Eight children (23%) were negative for HBsAg, HBsAb, and HBcAb: four (11.5%) had received immunoglobulin and a complete vaccine; in two children, it was not known whether they had received an immunoglobulin injection; in one child, the vaccine was incomplete; and in the last one, it was not known whether he had received immunoglobulin/vaccine. Their mothers had been administered lamivudine or tenofovir/emtricitabine during five and two pregnancies, respectively. No infant has chronic HBV infection (HBsAg) after prenatal mothers' antiretroviral therapy combined with a complete postnatal HBV protection. One child had HBcAb and HBsAb: it was not known whether she had received an immunoglobulin injection; the vaccine was incomplete. The mother had been administered lamivudine during the last trimester of pregnancy. CONCLUSION: Antiretroviral therapy in HBV/HIV coinfected women following current national HBV guidelines may prevent mother-to-child-transmission of HBV. Negativity of surrogate markers of vaccine-induced protection is frequent; large studies on long-term protection are needed.

Untreated highly viraemic pregnant women from Asia or sub-Saharan Africa often transmit hepatitis B virus despite serovaccination to newborns.

BACKGROUND & AIMS: Mother-to-child (MTC) hepatitis B virus (HBV) transmission has been mainly studied in Asia. The geographical origins of women and HBV genotypes differ in Europe. The aims were to determine the rate and risk factors of MTC HBV transmission from women with high HBV DNA loads in a maternity hospital in Paris, France. METHODS: Retrospective study of HIV-negative, HBs Ag-positive pregnant women with HBV DNA loads above 5 Log10 I.U/ml who were not given lamivudine or tenofovirDF during pregnancy between 2004 and 2011. RESULTS: Among 11 417 pregnant women, 437 (4%) showed a positive HBs Ag. Among these women, 52 had HBV DNA loads above 5 Log10 I.U/ml: 41, 10 and 1 born in Asia, sub-Saharan Africa and Europe respectively. Among the 52 women, 40 were eligible for the analysis: no antiviral therapy during pregnancy; children over 9 months old. Twenty-eight (70%) women were assessed, corresponding to 41 childbirths. Eleven children (27%) had positive HBs Ag, 14 (34%) had positive HBc and HBs Ab, 16 (39%) had positive HBs Ab only. The risk of having positive HBs Ag, according to maternal HBV DNA loads, was 14% for HBV DNA loads less or equal to 8 Log10 I.U/ml, 42% for HBV DNA loads over 8 Log10 I.U/ml, P = 0.04, but not related to the women's origin, HBV genotype. CONCLUSIONS: This study confirms that serovaccination does not fully protect newborns from MTC HBV transmission, when maternal HBV DNA loads exceed 5 Log10 I.U/ml, regardless of the women's origin or HBV genotype.

Hepatitis B virus (HBV) status of children born to HIV/HBV co-infected women in a French hospital: a cross-sectional study.

INTRODUCTION: Human Immunodeficiency Virus (HIV) Mother-To-Child-Transmission (MTCT) and prevention by combined antiretroviral therapy (cART) have been extensively studied. Hepatitis B Virus (HBV) MTCT from HIV/HBV co-infected women and prevention by antiretroviral therapy with dual activity have been poorly studied. The aim of the study was to assess HBV MTCT from HIV/HBV co-infected women in a developed country with a large access to cART. MATERIALS AND METHODS: HIV/HBV co-infected pregnant women attending the Obstetrics Department from 1st January 2000 to 1st January 2012 could be included in the study (NCT02044068). Antiretroviral therapy during pregnancy, injection of immunoglobulin and/or vaccine to newborns was retrospectively recorded. We assessed HBV status of children at least as old as two years. RESULTS: Forty nine (9.2%) from 530 HIV-infected women followed in the hospital were HIV/HBV co-infected. 34 (69.4%) had given birth to 57 children in the hospital. 13 of these women (22 children) were lost-to-follow-up, 21 women (35 children) could be studied. Twenty six children (74.3%) had HBs Ab at a protective level, 22 of them had received immunoglobulin at birth; 24 had received a complete vaccine schedule during the first six months of life (with immunoglobulin in 21 cases). The women had been given lamivudine or tenofovir/emtricitabine during eight and nine pregnancies respectively. Eight children (22.8%) were tested negative for HBs Ag, HBs Ab and HBc Ab: 4 (11.4%) had received immunoglobulin and a complete vaccine schedule; in two children, immunoglobulin was uncertain; in one child, the vaccine schedule was incomplete; in the last one, data about immunoglobulin and the vaccine schedule were lacking. The women had been given lamivudine or tenofovir/emtricitabine during five and two pregnancies respectively. One child had HBc Ab and HBs Ab, immunoglobulin was uncertain and the vaccine schedule was incomplete. The woman had been given lamivudine during the last trimester. CONCLUSIONS: Three quarters of the children were protected. HBs Ab were negative in more than a tenth of the children who had received immunoglobulin and a complete vaccine schedule, questioning on long-term protection and underlining the need of control.

Impact of low-level-viremia on HIV-1 drug-resistance evolution among antiretroviral treated-patients.

BACKGROUND: Drug-resistance mutations (DRAM) are frequently selected in patients with virological failure defined as viral load (pVL) above 500 copies/ml (c/mL), but few resistance data are available at low-level viremia (LLV). Our objective was to determine the emergence and evolution of DRAM during LLV in HIV-1-infected patients while receiving antiretroviral therapy (ART). METHODS: Retrospective analysis of patients presenting a LLV episode defined as pVL between 40 and 500 c/mL on at least 3 occasions during a 6-month period or longer while on the same ART. Resistance genotypic testing was performed at the onset and at the end of LLV period. Emerging DRAM was defined during LLV if never detected on baseline genotype or before. RESULTS: 48 patients including 4 naive and 44 pretreated (median 9 years) presented a LLV episode with a median duration of 11 months. Current ART included 2NRTI (94%), ritonavir-boosted PI (94%), NNRTI (23%), and/or raltegravir (19%). Median pVL during LLV was 134 c/mL. Successful resistance testing at both onset and end of the LLV episode were obtained for 37 patients (77%), among who 11 (30%) acquired at least 1 DRAM during the LLV period: for NRTI in 6, for NNRTI in 1, for PI in 4, and for raltegravir in 2. During the LLV period, number of drugs with genotypic resistance increased from a median of 4.5 to 6 drugs. Duration and pVL level of LLV episode, duration of previous ART, current and nadir CD4 count, number of baseline DRAM and GSS were not identified as predictive factors of resistance acquisition during LLV, probably due to limited number of patients. CONCLUSION: Persistent LLV episodes below 500 c/ml while receiving ART is associated with emerging DRAM for all drug classes and a decreasing in further therapeutic options, suggesting to earlier consider resistance monitoring and ART optimization in this setting.