Epidemiology and outcomes of vancomycin-resistant enterococcus infections: a systematic review and meta-analysis.

Vancomycin-resistant enterococci (VRE) cause many infections in the healthcare context. Knowledge regarding the epidemiology and burden of VRE infections, however, remains fragmented. We aimed to summarize recent studies on VRE epidemiology and outcomes in hospitals, long-term-care facilities (LTCFs) and nursing homes worldwide based on current epidemiological reports. We searched MEDLINE/PubMed, the Cochrane Library, and Web of Science for observational studies, which reported on VRE faecium and faecalis infections in in-patients published between January 2014 and December 2020. Outcomes were incidence, infection rate, mortality, length of stay (LOS), and healthcare costs. We conducted a meta-analysis on mortality (PROSPERO registration number: CRD42020146389). Of 681 identified publications, 57 studies were included in the analysis. Overall quality of evidence was moderate to low. VRE incidence was rarely and heterogeneously reported. VRE infection rate differed highly (1-55%). The meta-analysis showed a higher mortality for VRE faecium bloodstream infections (BSIs) compared with VSE faecium BSIs (risk ratio, RR 1.46; 95% confidence interval (CI) 1.17-1.82). No difference was observed when comparing VRE faecium vs VRE faecalis BSI (RR 1.00, 95% CI 0.52-1.93). LOS was higher in BSIs caused by E. faecium vs E. faecalis. Only three studies reported healthcare costs. In contrast to previous findings, our meta-analysis of included studies indicates that vancomycin resistance independent of VRE species may be associated with a higher mortality. We identified a lack of standardization in reporting outcomes, information regarding healthcare costs, and state-of-the-art microbiological species identification methodology, which may inform the set-up and reporting of future studies.

Bacterial aetiology and mortality in COPD patients with CAP: results from the German Competence Network, CAPNETZ.

BACKGROUND: Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality, and chronic obstructive pulmonary disease (COPD) is a frequent comorbidity. The bacterial aetiology of CAP-COPD and its possible associations with serum markers and mortality are incompletely understood. OBJECTIVES: 1) To assess the bacterial aetiology of CAP only and CAP-COPD, and 2) to study the association between bacterial aetiology, empirical antibiotic treatment, serum markers and mortality. METHODS: Of 1288 patients with CAP (57.0% males, age 59.0 years ± 18.5), 262 (20.3%) fulfilled the diagnostic criteria for COPD. Differences between subgroups were investigated using univariate analyses and corrected for multiple comparisons. RESULTS: Streptococcus pneumoniae was the most common pathogen (30.8% CAP only vs. 26.0% CAP-COPD, not significant). Haemophilus influenzae was significantly more frequent in CAP-COPD (5.6% CAP only vs. 26.0% CAP-COPD, P < 0.001). The number given adequate empirical antibiotic treatment was comparable (83.3% CAP only vs. 83.6% CAP-COPD, P > 0.05). The CAP-COPD group had worse CURB-65 and partial pressure of arterial oxygen levels than the CAP only group (P < 0.001). Partial pressure of arterial carbon dioxide levels were increased in CAP-COPD patients without pathogen detection (P < 0.001). Short- (P = 0.011) and long-term mortality (P = 0.006) were highest in CAP-COPD without pathogen detection. CONCLUSION: It is important to identify COPD patients with CAP. In particular, those without bacterial pathogen detection have more severe CAP and are at higher risk of dying. Better understanding of the aetiology could contribute to improved management and treatment of CAP in COPD patients.

Prevalence of nosocomial pathogens in German ambulances: the SEKURE study.

OBJECTIVE: The increasing prevalence of multidrug resistant bacteria is a problem in the inpatient care setting, and in the emergency care system. The aim of this observational, cross-sectional study was to evaluate the prevalence of pathogens on well-defined surfaces in German ambulances that have been designated as 'ready for service'. METHODS: After informed consent was obtained, ambulance surfaces were sampled with agar plates for microbiological examination during an unannounced visit. A standardised questionnaire was used to obtain information regarding the disinfection protocols used at each rescue station. RESULTS: Methicillin resistant staphylococcus aureus contamination was present in 18 sampling surfaces from 11 out of 150 ambulance vehicles (7%) that were designated as ready for service. Contact surfaces directly surrounding patients or staff were most frequently contaminated with pathogens. However, bacterial contamination was not related to annual missions, methods or frequency of disinfection. CONCLUSIONS: In accordance with previous studies, disinfection and cleaning of areas with direct contact to patients or staff seem to be the most challenging. This should also be reflected in disinfection guidelines and the related continuing education.

Chlamydia trachomatis prevalence, genotype distribution and identification of the new Swedish variant in Southern Germany.

PURPOSE: In Germany, reliable data about the prevalence of urogenital Chlamydia trachomatis infections, causative genotypes, as well as corresponding clinical, demographic and behavioural information are sparse. We, therefore, performed a prospective prevalence study including 1,003 sexually active volunteers of a Southern German city. METHODS: Study participants completed a standardised questionnaire and provided first void urine samples for analysis. Our screening strategy included the performance of two nucleic acid amplification tests with different target genes, enabling the detection of the new Swedish variant of C. trachomatis (nvCT). Direct genotyping of positive specimens was performed by sequence analysis of the ompA gene. RESULTS AND CONCLUSION: The overall prevalence of C. trachomatis infection was 4.2 % in women and 4.6 % in men. A relatively high prevalence of 8.3 % was found in men older than 25 years. Never using condoms was an independent risk factor for infection. The most common symptom was discharge; however, 64.5 % of infected females and all of the infected men were asymptomatic, supporting the need for screening programmes. The most frequently encountered genotypes were E (46.5 %), F (20.9 %) and K (14.0 %). Since the nvCT was detected in one female student, this is one of the rare studies that reports on the molecular identification of nvCT apart from Sweden.

[Epidemiology, diagnosis and treatment of adult patients with nosocomial pneumonia. S-3 Guideline of the German Society for Anaesthesiology and Intensive Care Medicine, the German Society for Infectious Diseases, the German Society for Hygiene and Microbiology, the German Respiratory Society and the Paul-Ehrlich-Society for Chemotherapy]. / Epidemiologie, Diagnostik und Therapie erwachsener Patienten mit nosokomialer Pneumonie. S-3 Leitlinie der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin e.V., der Deutschen Gesellschaft für Infektiologie e.V., der Deutschen Gesellschaft für Hygiene und Mikrobiologie e.V., der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e.V. und der Paul-Ehrlich-Gesellschaft für Chemotherapie e.V.

Nosocomial pneumonia (HAP) is a frequent complication of hospital care. Most data are available on ventilator-associated pneumonia. However infections on general wards are also increasing. A central issue are infections with multi drug resistant (MDR) pathogens which are difficult to treat particularly in the empirical setting potentially leading to inappropriate use of antimicrobial therapy. This guideline was compiled by an interdisciplinary group on the basis of a systematic literature review. Recommendations are made according to GRADE giving guidance for the diagnosis and therapy of HAP on the basis of quality of evidence and benefit/risk ratio. The guideline has two parts. First an update on epidemiology, spectrum of pathogens and antiinfectives is provided. In the second part recommendations for the management of diagnosis and treatment are given. Proper microbiologic work up is emphasized for knowledge of the local patterns of microbiology and drug susceptibility. Moreover this is the optimal basis for deescalation in the individual patient. The intensity of antimicrobial therapy is guided by the risk of infections with MDR. Structured deescalation concepts and strict limitation of treatment duration should lead to reduced selection pressure.

The burden of pneumococcal pneumonia - experience of the German competence network CAPNETZ.

BACKGROUND: Pneumococcal pneumonia is still an important cause of mortality. The objective of this study was to compare frequency, clinical presentation, outcome and vaccination status of patients with pneumococcal community-acquired pneumonia (CAP) to CAP due to other or no detected pathogen based on data of the German Network for community-acquired pneumonia (CAPNETZ). METHODS: Demographic, clinical and diagnostic data were recorded using standardized web-based data acquisition. Standardized microbiological sampling and work-up were conducted in each patient. RESULTS: 7400 patients with CAP from twelve clinical centers throughout Germany were included. In 2259 patients (32 %) a pathogen was identified, Streptococcus pneumonia being the most frequent (n = 676, 30 % of all patients with identified pathogens). Compared to those with non-pneumococcal pneumonia, patients with pneumococcal pneumonia were more frequently admitted to hospital (80 % vs. 66 %, p < 0.001), had higher CURB score values on admission, had more frequently pleural effusion (19 % vs. 14 %, p = 0.001) and needed more frequently oxygen insufflation (58 % vs. 44 %, p < 0.001). There was no relevant difference in overall mortality. CONCLUSIONS: Pneumococcal pneumonia was associated with a more severe clinical course demanding more medical resources as compared to non-pneumococcal pneumonia.

[Interdisciplinary management of a large Legionella outbreak in Germany]. / Interdisziplinäres Management eines länderübergreifenden Legionellenausbruchs.

Between December 2009 and the end of January 2010, the largest hitherto known outbreak of Legionella in Germany took place in the cities of Ulm and Neu-Ulm. Of a total of 64 patients involved, 60 patients had to be hospitalized, and 5 patients died from the infection. This event was caused by a wet cooling tower of a large air conditioning system in the city center of Ulm. The search for the source of the Legionella emission was extremely difficult, since these plants are neither notifiable nor subject to authorization in Germany. We report about the search for the source and the measures to control the outbreak. We also discuss communication and coordination during these investigations. Regulatory measures as proposed by the World Health Organization (WHO) and the European Network for Legionellosis (EWGLI) and already implemented in numerous other European countries would be desirable to prevent such outbreaks in the future.

[Community-acquired Legionella pneumonia : data from the CAPNETZ study]. / Ambulant erworbene Legionellenpneumonie : Aktuelle Daten aus dem CAPNETZ.

Legionella are present in the environment as well as in biofilms of water installation systems. Most Legionella live in amoebae. More than 51 different species of Legionella have been identified; however, most pneumonias are caused by Legionella pneumophila serogroup 1. Legionnaire's disease has an incidence of about 4% in Germany. Most cases of Legionnaire's disease are sporadic. Microbiological identification of Legionella can be achieved by cultivation of Legionella spp. on specific media, performing of Legionella-specific PCR from respiratory samples, or Legionella urinary antigen testing. Patients with severe underlying diseases, patients receiving immunosuppression, and patients who are heavy smokers have a predisposition to Legionnaire's disease. Men are significantly more often affected. Whereas outpatients show a mild clinical course, mortality for hospitalized patients is 11.2%. It can be assumed that only a minority of cases of Legionnaire's disease is recognized and reported in Germany.

[Epidemiology and Aetiology of Community-acquired Pneumonia (CAP)]. / Epidemiologie und Erreger bei ambulant erworbener Pneumonie (CAP).

Community-acquired pneumonia is a frequent disease. Case-fatality rate and incidence are increasing with age. The German nation-wide competence network CAPNETZ presents reliable data on aetiology and course of the disease, based on more than 9000 prospectively observed patients. This review discusses current CAPNETZ-publication and their impact on daily clinical practice. The most frequent isolated pathogen isolated was STREPTOCOCCUS PNEUMONIAE. According to CAPNETZ results, the importance of atypical pathogens (i. e. Mycoplasma spp., Chlamydia spp., Legionella spp.) may have been overestimated in older studies: CHLAMYDIA PNEUMONIAE (< 1 %) are rarely found, and the most frequent atypical pathogen, Mycoplasma spp., causes only mild disease in younger patients resulting in a very low case-fatality-rate (0.7 %). Only hospitalized patients with legionella infections are at an increased risk to die. Gram-negative ENTEROBACTERIACEAE and PSEUDOMONAS AERUGINOSA are rare, restricted to high-risk patient groups (e. g. mulitmorbidity, enteral tube feeding), but are associated with an increased case-fatality rate.

How deadly is seasonal influenza-associated pneumonia? The German Competence Network for Community-Acquired Pneumonia.

The emergence of new influenza virus subtypes has rekindled the interest in the clinical course and outcome of patients with influenza-associated pneumonia. Based on prospective data from 5,032 patients with community-acquired pneumonia (CAP) included in the German Competence Network for Community-Acquired Pneumonia (CAPNETZ), we studied the incidence, clinical characteristics and outcome of patients with influenza-associated CAP and compared these findings with patients without influenza. Diagnosis relied on a positive PCR for influenza in throat washings. 160 patients with influenza-associated CAP were identified (3.2% of total population, 12% of those with defined aetiology). 34 (21%) patients with seasonal influenza had a concomitant pathogen (mostly Streptococcus pneumoniae). Patients with influenza-associated CAP were significantly older, had been vaccinated less often and had preceding antibacterial treatment less often. 30-day mortality was low (4.4%) and not different to that of patients with pneumonia caused by bacterial (6.2%) or viral (other than influenza) pathogens (4%). Patients with influenza plus a bacterial pathogen (mixed influenza-associated pneumonia) had a higher mortality than those with pure influenza-associated pneumonia (9% versus 3.2%). Mortality was higher in patients with mixed compared with pure influenza-associated pneumonia. However, we could not observe any excess mortality in patients with influenza-associated pneumonia.

Is domestic tap water a risk for infections in neutropenic patients?

BACKGROUND: Home care has become popular in the management of hemato-oncologic patients. Therefore, we conducted a prospective study to assess whether tap water from the domestic environment of neutropenic patients poses a risk for infections from the waterborne pathogens nontuberculous mycobacteria (NTM), Legionella spp., and Pseudomonas aeruginosa. MATERIALS AND METHODS: Tap water samples were taken in the homes of 65 hemato-oncologic patients who were discharged from the hospital whilst neutropenic and had a suspected period of neutropenia of a minimum of 10 days. Selective culture for Legionella, P. aeruginosa, and NTM was performed. Patients who required hospital readmission were monitored for infection with the aforementioned pathogens over the following 3 months. RESULTS: NTM were cultured in 62 (95.4%) households in concentrations from 1 to 1,000 CFU/500 ml. The facultative pathogenic species Mycobacterium chelonae (58.5% of taps) and M. mucogenicum (38.5% of taps) were most frequently detected. Legionella spp. was cultured from six households (9.2%), including five households with L. pneumophila in concentrations from 25 to 2,500 CFU/500 ml. P. aeruginosa was found in seven households (10.8%) in concentrations from 5 to 2,500 CFU/500 ml. While clinical infection with Legionella spp. was not detected in any patients, infection with M. chelonae and P. aeruginosa occurred in one and seven patients, respectively. However, transmission from household water could not be confirmed. CONCLUSION: Although the risk of infection from household water-borne pathogens appears low, preventive measures may be considered on an individual basis in patients with long-term immunosuppression as well as in patients with long-term central-vascular catheterization.

Subtypes and variants of Mycoplasma pneumoniae: local and temporal changes in Germany 2003-2006 and absence of a correlation between the genotype in the respiratory tract and the occurrence of genotype-specific antibodies in the sera of infected patients.

Mycoplasma pneumoniae is a frequent cause of community-acquired pneumonia. Three subtypes and three variants of M. pneumoniae have been described showing sequence differences in the main P1 adhesin. Between 2003 and 2006 we collected respiratory tract samples of adult outpatients with symptoms of pneumonia in a German nationwide network and detected M. pneumoniae by real-time PCR in 140 specimens. The strains were typed by sequencing and demonstrated the circulation of subtypes 1 and 2 and variants 2a and 2b. The overall number of isolates belonging to the two variant genotypes increased during the investigation period but the relationship of subtypes and variants within the participating local centres varied strongly. ELISA experiments using sera of acute-phase patients with a known M. pneumoniae type in the respiratory tract resulted in no correlation of IgA and IgG antibodies to subtype- and variant-specific regions of the P1 gene with the genotype of the M. pneumoniae strain causing the actual infection.

Preliminary report: outbreak of Legionnaires disease in the cities of Ulm and Neu-Ulm in Germany, December 2009 - January 2010.

Currently an investigation is ongoing to explore and control an outbreak of Legionnaires disease, affecting 65 people as of 22 January 2010, in the cities of Ulm and Neu-Ulm, south-west Germany. A hitherto unidentified wet cooling system in these twin cities is considered as the most likely source of infection.

A novel IS26 structure surrounds blaCTX-M genes in different plasmids from German clinical Escherichia coli isolates.

This report focuses on the molecular characterization of 22 extended-spectrum beta-lactamase-producing Escherichia coli isolates collected in a German university hospital during a period of 9 months in 2006. Relationship analysis of clinical isolates was done via PFGE, multilocus sequence typing, plasmid profiling and additionally PCR for bla(ESBL) detection and determination of phylogroups. After conjugal transfer, plasmid isolation and subsequent PCR for bla(ESBL) detection and determination of incompatibility groups were performed. Using one-primer walking, up to 3600 bp upstream and downstream of different bla(CTX-M) genes could be sequenced. beta-Lactamases found were TEM-1 (n=14), SHV-5 (n=1) and a wide variety of CTX-M types (n=21), i.e. CTX-M-15 (n=12), CTX-M-1 (n=4), CTX-M-14 (n=2), CTX-M-9 (n=1), CTX-M-3 (n=1) and one new type, CTX-M-65 (n=1). In 18 isolates, bla(ESBL) genes were located on conjugative plasmids of sizes between 40 and 180 kbp belonging to incompatibility groups FII (n=9), N (n=5) and I1 (n=4). bla(CTX-M) was found to be associated with the common elements ISEcp1, IS26 and IS903-D, but with unusual spacer sequences for ISEcp1 in two isolates. These insertion sequences, connected to bla(CTX-M) as well as other genes, were located between two IS26 elements in a configuration that has not yet been described. The results reveal the emergence of bla(ESBL), predominantly bla(CTX-M), located on different plasmids harboured by genotypically different E. coli strains. The identical gene arrangement in the bla(CTX-M) neighbourhood in plasmids of different incompatibility groups indicates a main role of IS26 in distribution of mobile resistance elements between different plasmids.

Occurrence of macrolide-resistant Mycoplasma pneumoniae strains in Germany.

In a total of 167 respiratory tract specimens from adult outpatients with confirmed Mycoplasma pneumoniae pneumonia, sampled between 2003 and 2008, and a further 99 isolates obtained from patients between 1991 and 2009 in Germany, M. pneumoniae was tested for macrolide resistance. Using PCR, real-time PCR and sequencing of the 23S rRNA gene, 1.2% of M. pneumoniae in the respiratory tract samples and 3.0% of the isolates were found to be resistant. The results indicate a limited but not negligible importance of macrolide-resistant M. pneumoniae in the population investigated, which requires the monitoring of macrolide susceptibility of isolates or the testing of respiratory samples by molecular methods.

Community-acquired pneumonia through Enterobacteriaceae and Pseudomonas aeruginosa: Diagnosis, incidence and predictors.

The aim of the present study was to determine the relevance of the presence of Enterobacteriaceae (EB) and Pseudomonas aeruginosa (PA) in patients with community-acquired pneumonia (CAP) and how the true incidence of these pathogens can be assessed. Based on prospective data from 5,130 patients with CAP included in the German Competence Network for Community-Acquired Pneumonia (CAPNETZ), the incidence, clinical characteristics, outcome and predictors of patients with CAP due to EB and PA were studied applying strict case definitions. The incidence of EB was 67 (1.3%) out of 5,130, including 27 patients with bacteraemia. PA was found in 22 (0.4%) out of 5,130 patients. These microorganisms were judged to be indeterminate pathogens in an additional 172 and 27 isolates, respectively. Patients with indeterminate pathogens differed considerably from those with definite isolates in terms of clinical presentation, comorbidity, pneumonia severity and outcome. Independent risk factors for EB included cardiac and cerebrovascular disease, and for PA chronic respiratory disease and enteral tube feeding. The 30-day mortality was significantly higher in patients with definite pathogens. In the present large population, the incidence of CAP due to EB/ PA was low. The risk of the presence of these pathogens can be assessed using several predictors, which may identify those patients in need of an extended diagnostic work-up and initial antimicrobial treatment.

Procalcitonin predicts patients at low risk of death from community-acquired pneumonia across all CRB-65 classes.

The aim of the present study was to investigate the prognostic value, in patients with community-acquired pneumonia (CAP), of procalcitonin (PCT) compared with the established inflammatory markers C-reactive protein (CRP) and leukocyte (WBC) count alone or in combination with the CRB-65 (confusion, respiratory rate >or=30 breaths x min(-1), low blood pressure (systolic value <90 mmHg or diastolic value or=65 yrs) score. In total, 1,671 patients with proven CAP were enrolled in the study. PCT, CRP, WBC and CRB-65 score were all determined on admission and patients were followed-up for 28 days for survival. In contrast to CRP and WBC, PCT levels markedly increased with the severity of CAP, as measured by the CRB-65 score. In 70 patients who died during follow-up, PCT levels on admission were significantly higher compared with levels in survivors. In receiver operating characteristic analysis for survival, the area under the curve (95% confidence interval) for PCT and CRB-65 was comparable (0.80 (0.75-0.84) versus 0.79 (0.74-0.84)), but each significantly higher compared with CRP (0.62 (0.54-0.68)) and WBC (0.61 (0.54-0.68)). PCT identified low-risk patients across CRB classes 0-4. In conclusion, procalcitonin levels on admission predict the severity and outcome of community-acquired pneumonia with a similar prognostic accuracy as the CRB-65 score and a higher prognostic accuracy compared with C-reactive protein and leukocyte count. Procalcitonin levels can provide independent identification of patients at low risk of death within CRB-65 (confusion, respiratory rate >or=30 breaths x min(-1), low blood pressure (systolic value <90 mmHg or diastolic value or=65 yrs) risk classes.

Changes in Escherichia coli resistance patterns during and after antibiotic therapy: a longitudinal study among outpatients in Germany.

There is worldwide concern about the appearance and rise of bacterial resistance to commonly used antibiotics. Although the gut is an important reservoir for resistant Escherichia coli, data from large-scale epidemiological studies concerning the colonisation dynamics of the normal gut flora with resistant E. coli during and after antibiotic therapy are sparse. Accordingly, a large community-based study was conducted to ascertain changes in the prevalence of resistant E. coli during and after antibiotic treatment. Stool samples before, during and after antibiotic therapy were obtained from 541 patients (aged >/=40 years) with a febrile infection who attended a general practitioner in southern Germany. The MICs of commonly prescribed antibiotics for E. coli isolates from the stools were determined. The prevalence of resistance to the corresponding antibiotics rose from 18% to 38%, from 29% to 58% and from 33% to 67% during treatment with beta-lactam antibiotics, doxycycline and co-trimoxazole, respectively. Prevalences of resistance in the E. coli isolates also rose for other antibiotic classes. With the exception of co-trimoxazole resistance, prevalences of resistance returned to baseline levels in <2 weeks after the cessation of antibiotic therapy. Thus, there was a substantial, but rapidly reversible, increase in the prevalence of resistant E. coli isolates during antibiotic treatment.

Value of whole-body washing with chlorhexidine for the eradication of methicillin-resistant Staphylococcus aureus: a randomized, placebo-controlled, double-blind clinical trial.

BACKGROUND: Whole-body washing with antiseptic solution has been widely used as part of eradication treatment for colonization with methicillin-resistant Staphylococcus aureus (MRSA), but evidence for the effectiveness of this measure is limited. OBJECTIVE: To study the efficacy of whole-body washing with chlorhexidine for the control of MRSA. DESIGN: Randomized, placebo-controlled, double-blinded clinical trial. SETTING: University Hospital of Heidelberg and surrounding nursing homes. PATIENTS: MRSA carriers who were not treated concurrently with antibiotics effective against MRSA were eligible for the study. INTERVENTION: Five days of whole-body washing with either 4% chlorhexidine solution (treatment group) or with a placebo solution. All patients received mupirocin nasal ointment and chlorhexidine mouth rinse. The outcome was evaluated 3, 4, 5, 9, and 30 days after treatment with swab samples taken from several body sites. RESULTS: Of 114 patients enrolled in the study (56 in the treatment group and 58 in the placebo group), 11 did not finish treatment (8 from the treatment group and 3 from the placebo group [P=.02]). At baseline, the groups did not differ with regard to age, sex, underlying condition, site of MRSA colonization, or history of MRSA eradication treatment. Eleven patients were MRSA-free 30 days after treatment (4 from the treatment group and 7 from the placebo group [P=.47]). Only groin-area colonization was significantly better eradicated by the use of chlorhexidine. The best predictor for total eradication was a low number of body sites positive for MRSA. Adverse effects were significantly more frequent in the treatment group than in the placebo group (any symptom, 71% vs 33%) but were reversible in most cases. CONCLUSION: Whole-body washing can reduce skin colonization, but it appears necessary to extend eradication measures to the gastrointestinal tract, wounds, and/or other colonized body sites if complete eradication is the goal.