Antimicrobial susceptibility of bacteria causing urinary tract infections in Latin American hospitals: results from the SENTRY Antimicrobial Surveillance Program (1997)

Objectives: To evaluate the antimicrobial susceptibility patterns among 469 pathogens isolated as a significant cause of urinary tract infections in 10 Latin American medical centers.
Methods: Consecutively collected isolates were susceptibility tested by broth microdilution methods, and selected isolates were characterized by molecular typing methods.
Results: Escherichia coli and Klebsiella spp. isolates revealed high rates of resistance to broad-spectrum penicillins and to fluoroquinolones. Ceftazidime MICs of ≥2 mg/L, suggesting the production of extended-spectrum β-lactamases (ESBLs), were observed in 37.7% of K. pneumoniae and 8.3% of Escherichia coli isolates. Enterobacter spp. isolates were characterized by high resistance rates to ciprofloxacin (35%) and to ceftazidime (45%), but they generally remained susceptible to cefepime (95% susceptible). Pseudomonas aeruginosa and Acinetobacter spp. were highly resistant to ciprofloxacin and ceftazidime. Imipenem was active against 80% of P. aeruginosa and 93% of Acinetobacter spp. isolates.
Conclusions: Our results demonstrate a high level of resistance to various classes of antimicrobial agents among isolates causing nosocomial urinary tract infections in Latin American hospitals. Clonal dissemination of ESBL-producing K. pneumoniae strains was infrequent.     

Introduction: Evolving needs in respiratory tract infections

Two issues that have become clinically relevant to the treatment of pneumonia over the past few years are the development of antibiotic resistance among respiratory pathogens and the increasing importance of the atypical respiratory pathogens— Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella spp.
Resistance has become an important issue in Streptococcus pneumoniae , methicillin-resistant Staphylococcus aureus and Gram-negative rods. The ways by which bacteria become resistant to antibiotics include production of antibiotic-modifying enzymes, reduced access to target sites, efflux of antibiotic, change in the bacterial target site and the bypassing of inhibited pathways. In Streptococcus pneumoniae that are penicillin resistant, the mechanism is through alteration of the target site for penicillins (penicillin-binding proteins) and this may also confer resistance to some cephalosporins. Multidrug resistance has also been reported in some strains of pneumococci. Of particular concern is resistance to macrolides mediated by the ermAM gene, which also confers resistance to lincosamides and streptogramin-B drugs. In Staphylococcus aureus , resistance to virtually all β-lactam drugs is mediated by acquisition of the mecA gene, which codes for the drug-resistant β-lactam target PBP2a.
Antimicrobials are now needed that have enhanced activity against aerobic Gram-negative rods, atypical respiratory pathogens and Gram-positive cocci.     

Integrons and multidrug resistance among Escherichia coli causing community-acquired urinary tract infection in southern India

Antimicrobial resistance genes are often clustered in integrons, genetic elements capable of recombination. There is a paucity of data on the prevalence and role of integrons from community-acquired infections in developing countries where resistance to co-trimoxazole is high. We determined the prevalence of integrons among Escherichia coli causing community-acquired urinary tract infection (UTI). Consecutive isolates of E. coli obtained from UTI of pregnant women at the Christian Medical College Hospital, Vellore, India, during 2002 were included. All isolates were tested for susceptibility to 16 antimicrobials using the disc diffusion method and for integrons of classes 1 and 2 by PCR. Of the 58 isolates tested, 28 (48.3%) were resistant to co-trimoxazole and trimethoprim. All these isolates carried integrons. Three additional isolates were sulfonamide resistant but integron negative. Class 1 integrons were present in 21 (36.2%) isolates. Resistance to ampicillin (p=0.000), nalidixic acid (p=0.001), chloramphenicol (p=0.02), tetracycline (p=0.004) and gentamicin (p=0.02) was significantly more common in isolates with integrons. DNA sequencing of two isolates with integrons showed the presence of aadA, dfr1 and dfr7 genes. This study demonstrated that integrons are widely prevalent in India and that they might play a role in multidrug resistance in E. coli from community-acquired UTI.     

Antibiotic resistance of Escherichia coli from community-acquired urinary tract infections in relation to demographic and clinical data

This prospective study determined the antibiotic susceptibility of 164 isolates of Escherichia coli from the urine of 164 patients (112 female, 52 male; mean age of 54.12 years) with community-acquired urinary tract infection (UTI). Half of the isolates were from uncomplicated UTI and half from complicated UTI (52 males and 34 females). Overall, 57.3% of isolates were resistant to ampicillin, 25% to co-trimoxazole, 20.1% to nalidixic acid, 14% to norfloxacin and ciprofloxacin, and 0% to fosfomycin and nitrofurantoin. Of the 82 isolates from complicated UTI, 16 (19.5%) were resistant to norfloxacin and ciprofloxacin, compared with seven (8.5%) from uncomplicated UTI (p 0.043). Isolates from patients aged >50 years were significantly more resistant than those from patients aged <50 years for nalidixic acid (p 0.007) and the fluoroquinolones tested (p 0.015). Resistance to fluoroquinolones was 25% (13/52) in males and 9% (10/112) in females (p 0.006). For patients with and without previous antimicrobial therapy, there was a significant difference only for resistance to nalidixic acid (p < 0.001) and the fluoroquinolones (p 0.011). There were adequate susceptibility rates to fosfomycin, nitrofurantoin and the fluoroquinolones for empirical use in the treatment of acute uncomplicated UTI. In order to interpret cumulative susceptibility data from the primary healthcare setting, it is necessary to take into account the type of UTI (uncomplicated vs. complicated), previous antimicrobial therapy, and the sex and age of each patient.     

Predictors of patient-initiated reconsultation for lower respiratory tract infections in general practice

Reconsultation for lower respiratory tract infection (LRTI) is common in general practice, but those who reconsult rarely have more significant illness warranting antibiotics. Knowledge of factors that predict patient-initiated reconsultation may allow clinicians to address specific issues during the initial consultation that could reduce reconsultations. Thirty-three per cent of a cohort of 431 LRTI patients in a randomised controlled trial reconsulted. Excluding 35 patients with GP-requested reconsultation left 28% (112/396) with a patient-initiated reconsultation during 28-day follow-up. Patient-reported dyspnoea and concerns that persisted after the initial consultation independently predicted patient-initiated reconsultation.     

Resistance patterns of selected respiratory tract pathogens in Poland

This study presents the results of a survey of the in-vitro susceptibility to antimicrobial agents of major pathogens responsible for community-acquired respiratory tract infections in Poland during 2002-2004. The collection of 1184 bacterial isolates comprised 398 Streptococcus pneumoniae, 344 Haemophilus influenzae, 302 Streptococcus pyogenes and 140 Moraxella catarrhalis. Among the pneumococcal isolates, 16.8% were penicillin-non-susceptible (PNSP), of which 80.6% were identified as multidrug-resistant. Overall, 9.0% of H. influenzae isolates were beta-lactamase-positive, although this percentage increased noticeably in the third year of the study. Based on PCR results, 12.8% of H. influenzae isolates were identified as low-level beta-lactamase-negative, ampicillin-resistant (BLNAR), and one isolate as low-level beta-lactamase-positive, amoxycillin-clavulanic acid-resistant (BLPACR). Pulsed-field gel electrophoresis (PFGE) classified 45 H. influenzae isolates with altered penicillin-binding proteins into 15 PFGE types, including two predominant types (with four and six sub-types) containing 15 and ten isolates, respectively. Resistance to tetracycline, erythromycin and clindamycin was found in 20.9%, 8.9% and 4.6% of S. pyogenes isolates, respectively. The production of beta-lactamase characterised 91.4% of M. catarrhalis isolates. In summary, the overall occurrence of PNSP in Poland remains stable, although there was a noticeable increase in the proportion of fully-resistant isolates. A rising trend in the prevalence of beta-lactamase producers and low-level BLNAR isolates was observed among Polish isolates of H. influenzae.     

Antiadhesive and antibiofilm activity of hyaluronic acid against bacteria responsible for respiratory tract infections

To address the problem of limited efficacy of existing antibiotics in the treatment of bacterial biofilm, it is necessary to find alternative remedies. One candidate could be hyaluronic acid; this study therefore aimed to evaluate the in vitro antiadhesive and antibiofilm activity of hyaluronic acid toward bacterial species commonly isolated from respiratory infections. Interference exerted on bacterial adhesion was evaluated by using Hep‐2 cells, while the antibiofilm activity was assessed by means of spectrophotometry after incubation of biofilm with hyaluronic acid and staining with crystal violet. Our data suggest that hyaluronic acid is able to interfere with bacterial adhesion to a cellular substrate in a concentration‐dependent manner, being notably active when assessed as pure substance. Moreover, we found that Staphylococcus aureus biofilm was more sensitive to the action of hyaluronic acid than biofilm produced by Haemophilus influenzae and Moraxella catarrhalis. In conclusion, hyaluronic acid is characterized by notable antiadhesive properties, while it shows a moderate activity against bacterial biofilm. As bacterial adhesion to oral cells is the first step for colonization, these results further sustain the role of hyaluronic acid in prevention of respiratory infections.     

High incidence of the virus among respiratory pathogens in children with lower respiratory tract infection in northwestern China

Lower respiratory tract infection (LRTI) is one of the major reasons for childhood mortality that threaten the health of the public. We aimed to investigate the epidemiological pathogens and their infection analysis among children with LRTI. Sputum specimens were collected for polymerase chain reaction detection and microbiological tests to identify the viral infection and bacterial infection. The serological specimens were separated from venous blood using for Mycoplasma pneumoniae and Chlamydia pneumoniae detection. The virus was confirmed in 86.2% of the children. Human rhinovirus (38.3%), respiratory syncytial virus (32.1%), and parainfluenza virus type 3 (27.2%) were the most frequently identified pathogens. Patients with viral and bacterial coinfection showed younger age (p = 0.032), a higher proportion of wheezing rales (p = 0.032), three depressions sign (p = 0.028), and tachypnea (p = 0.038), and more likely associated with severe pneumonia (p = 0.035). Additionally, older children were more susceptible to viral-atypical bacterial coinfection (p = 0.032). Vomiting (p = 0.011) and fever (p = 0.003) were more likely to occur in children with viral-atypical bacterial coinfection. Attention should be paid to the virus infection of LRTI, as viral-bacterial coinfection and viral-atypical bacterial co-infection may have a detrimental impact on the gravity of LTRI.     

Antimicrobial susceptibility of Gram-positive bacteria isolated from European medical centres: results of the Daptomycin Surveillance Programme (2002–2004)

The antimicrobial susceptibility patterns of 9322 contemporary (2002-2004) gram-positive bacterial isolates collected from 31 medical centres in 14 countries in Europe were evaluated by broth microdilution methods according to CLSI guidelines. The isolates collected comprised Staphylococcus aureus (4842 isolates), coagulase-negative staphylococci (CoNS; 1942 isolates), Enterococcus faecalis (1147 isolates), Enterococcus faecium (391 isolates), beta-haemolytic streptococci (660 isolates) and viridans group streptococci (340 isolates). The organisms were tested against daptomycin and more than 20 comparator agents in Mueller-Hinton broth, supplemented with calcium to 50 mg/L when testing daptomycin. Overall, methicillin (oxacillin) resistance rates were 26.7% and 77.0% for S. aureus (MRSA) and CoNS, respectively, and the vancomycin resistance rate among enterococci was 6.1%. MRSA rates varied from 0.6% in Sweden to 40.2-43.0% in Belgium, Greece, Ireland, the UK and Israel, and VRE rates varied from 0% in Switzerland to 21.2% in Ireland. More than 99.9% of isolates tested were considered susceptible to daptomycin according to breakpoints established by the United States Food and Drug Administration and the CLSI. Daptomycin was active against all gram-positive species, with the highest MIC being 2, 8, 0.5 and 2 mg/L for staphylococci, enterococci, beta-haemolytic streptococci and viridans group streptococci, respectively. Daptomycin activity was not influenced adversely by resistance to other agents among staphylococci or enterococci. This novel lipopeptide (daptomycin) appears to be an excellent alternative therapeutic option for serious infections caused by multidrug-resistant gram-positive organisms isolated in Europe.     

Activity of telithromycin and comparators against isolates of Legionella pneumophila collected from patients with community-acquired respiratory tract infections: PROTEKT Years 1–5

The in-vitro activity of telithromycin and comparator antibacterial agents was determined against clinical isolates of Legionella pneumophila collected in the PROTEKT surveillance study. In total, 133 isolates were collected between 1999 and 2004 from 13 countries (Australia, Belgium, Czech Republic, France, Germany, Hungary, Ireland, Italy, Japan, Portugal, Spain, Sweden and the USA). MICs were determined by broth microdilution. Telithromycin maintained activity between Year 1 (MIC(90) 0.015 mg/L) and Year 5 (MIC(90) 0.03 mg/L), as did the comparator antibacterial agents. Telithromycin appears to be a candidate for coverage of legionellosis in the empirical treatment of community-acquired respiratory tract infection.     

Risk factors of multidrug-resistant bacteria in community-acquired urinary tract infections

BackgroundUrinary tract infections (UTIs) are one of the most seen infection among community.ObjectivesIn this cross-sectional study we aimed to investigate the risk factors of multidrug-resistant (MDR) bacteria that caused community-acquired UTI (CA-UTI).MethodsConsecutive patients admitted to the Urology and Infectious Diseases policlinics with the diagnosis of CA-UTI were included in the study. A standard form including possible predisposing factors for MDR bacteria was applied.ResultsIn total, 240 patients (51.3% females) were enrolled in the study. The mean age of participants were 59.8 ± 18.3 years old. Escherichia coli (n =166; 69.2%)was the most frequently isolated bacteria and its incidence was higher in females than in males (p=0.01). In total, 129 (53.8%) of the identified pathogens were MDR bacteria. According to multivariate analysis, the use of antibiotics three or more times increased the risk of infection with MDR bacteria by 4.6 times, the history of urinary tract infection in the last 6 months by 2 times, being male and over 65 years old by 3 times.ConclusionDoctors should consider prescribing broad-spectrum antibiotics in patients with severe UTIs with a history of UTI, advanced age, male gender, and multiple antibiotic usage, even if they have a CA-UTI.     

Achromobacter xylosoxidans respiratory tract infections in cystic fibrosis patients

Achromobacter xylosoxidans is a ubiquitous Gram‐negative non‐fermenting rod, recently characterized as an emerging pathogen in cystic fibrosis (CF) patients. Its pathogenic potential and prevalent transmission routes are still unclear. This study investigated the PFGE genetic pattern and antimicrobial resistance profile of 42 A. xylosoxidans isolates obtained over 4 years from the respiratory tract of 22 CF patients. By genotypic analysis, 31 isolates were attributed to 8 distinct PFGE patterns (A–H), whereas 11 isolates were not typable because their DNA was not restricted by XbaI and DraI restriction enzymes. The majority of the isolates showed multidrug resistance; imipenem and piperacillin were the most active drugs. During the course of A. xylosoxidans chronic infection forced expiratory volume and body mass index values were not significantly lowered. The demonstration of widespread antibiotic resistance underscores the importance of antibiogram‐directed therapy. Our data suggest that in some cases the infection may have been acquired from other patients or from a common contaminated source. Further epidemiological studies may be important for the design and implementation of prophylactic measures in CF centers.     

Diagnostic accuracy of point-of-care tests in acute community-acquired lower respiratory tract infections. A systematic review and meta-analysis

BackgroundPoint-of-care tests could be essential in differentiating bacterial and viral acute community-acquired lower respiratory tract infections and driving antibiotic stewardship in the community.ObjectivesTo assess diagnostic test accuracy of point-of-care tests in community settings for acute community-acquired lower respiratory tract infections.Data sourcesMultiple databases (MEDLINE, EMBASE, Web of Science, Cochrane Library, Open Gray) from inception to 31 May 2021, without language restrictions.Study eligibility criteriaDiagnostic test accuracy studies involving patients at primary care, outpatient clinic, emergency department and long-term care facilities with a clinical suspicion of acute community-acquired lower respiratory tract infections. The comparator was any test used as a comparison to the index test. In order not to limit the study inclusion, the comparator was not defined a priori.Assessment of risk of biasFour investigators independently extracted data, rated risk of bias, and assessed the quality using QUADAS-2.Methods of data synthesisThe measures of diagnostic test accuracy were calculated with 95% CI.ResultsA total of 421 studies addressed at least one point-of-care test. The diagnostic performance of molecular tests was higher compared with that of rapid diagnostic tests for all the pathogens studied. The accuracy of stand-alone signs and symptoms or biomarkers was poor. Lung ultrasound showed high sensitivity and specificity (90% for both) for the diagnosis of bacterial pneumonia. Rapid antigen-based diagnostic tests for influenza, respiratory syncytial virus, human metapneumovirus, and Streptococcus pneumoniae had sub-optimal sensitivity (range 49%–84%) but high specificity (>80%).DiscussionPhysical examination and host biomarkers are not sufficiently reliable as stand-alone tests to differentiate between bacterial and viral pneumonia. Lung ultrasound shows higher accuracy than chest X-ray for bacterial pneumonia at emergency department. Rapid antigen-based diagnostic tests cannot be considered fully reliable because of high false-negative rates. Overall, molecular tests for all the pathogens considered were found to be the most accurate.     

Outcomes in lower respiratory tract infections and the impact of antimicrobial drug resistance

Numerous published studies have documented the rapid rise in antimicrobial drug resistance among common respiratory pathogens, particularly Streptococcus pneumoniae . Yet, surprisingly few studies have evaluated the impact of these in vitro findings on clinical outcomes. Outcomes research is the measurement of the impact of illness and the effect of treatment on clinically relevant end-points. Studies of patients with community-acquired pneumonia have established certain expected rates of outcomes, including mortality, clinical complications, and time to resolution of symptoms. Recent studies have identified specific processes of care and treatment choices that have an impact upon these outcomes. However, there are no well-controlled studies that provide definitive estimates of the magnitude of the impact of antimicrobial therapy on these outcomes for patients with community-acquired pneumonia or other respiratory tract infections, such as acute exacerbations of chronic bronchitis. Most studies of the impact of drug resistance on outcomes for patients with respiratory tract infections have focused on the impact of β-lactam drug resistance on outcomes for patients with community-acquired pneumococcal pneumonia. In general, these studies have demonstrated that outcomes are not affected by current levels of drug resistance, but most studies are hampered by small sample size, inability to control adequately for severity of illness and concordance of therapy, and inclusion of few subjects with high-level drug resistance. Additional studies are urgently needed to assess better whether the current empiric treatment guidelines are adequate or will need to be adjusted as patterns of resistance continue to evolve.     

Changes in the characteristics of community-onset fluoroquinolone-resistant Escherichia coli isolates causing community-acquired acute pyelonephritis in South Korea

PurposeThis study aimed to examine the changes in the characteristics of community-onset fluoroquinolone-resistant (FQ-R) Escherichia coli isolates causing community-acquired acute pyelonephritis (APN) in South Korea.MethodsBlood or urine samples were prospectively collected from patients aged ≥15 years with community-acquired APN who were admitted to one of the eight Korean hospitals included in this study between September 2017 and August 2018. Phylogenetic typing, multilocus sequence typing, and molecular characterization of β-lactamase resistance and plasmid-mediated quinolone resistance (PMQR) determinants were performed. The data were compared with those from a previous study with the same design conducted in 2010–2011.ResultsA total of 300 and 346 isolates were identified in 2010–2011 and 2017–2018, respectively. Among them, 76 (22.0%) and 77 (25.7%) FQ-R isolates were identified in 2010–2011 and 2017–2018, respectively. A significantly higher antimicrobial resistance against third-to fourth-generation cephalosporins, including cefotaxime (23.9% vs. 77.9%, P < 0.001), were observed among FQ-R isolates in 2017–2018 than among those in 2010–2011. A higher proportion of ST131 isolates (27.6% vs. 66.2%, P < 0.001), as well as isolates that had extended-spectrum β-lactamase (ESBL)/plasmid-mediated AmpC β-lactamase (PABL) (23.7% vs. 79.2%, P < 0.001), was observed in 2017–2018 than in 2010–2011. Further, more PMQR determinants (11.8% vs. 40.8%, P < 0.001) were observed in 2017–2018 than in 2010–2011.ConclusionsAmong uropathogenic FQ-R E. coli isolates in South Korea, the prevalence of ST131 and the proportion of isolates containing ESBL and/or PMQR determinants have increased.     

A critical assessment of published guidelines and other decision-support systems for the antibiotic treatment of community-acquired respiratory tract infections

Guidelines are an important means by which professional associations and governments have sought to improve the quality and cost-effectiveness of disease management for infectious diseases. Prescribing of initial antibiotic therapy for community-acquired respiratory tract infections (RTIs) is primarily empiric and physicians may often have a limited appreciation of bacterial resistance. Recent guidelines for managing RTIs have adopted a more evidence-based approach. This process has highlighted important gaps in the existing knowledge base, e.g. concerning the impact of resistance on the effectiveness of oral antibiotics for outpatient community-acquired pneumonia and the level of resistance that should prompt a change in empiric prescribing. In upper RTIs, the challenge is to identify patients in whom antibiotic therapy is warranted. Concentrated, sustained efforts are needed to secure physicians' use of guidelines. The information should be distilled into a simple format available at the point of prescribing and supported by other behavioral change techniques (e.g. educational outreach visits). Advances in information technology offer the promise of more dynamic, computer-assisted forms of guidance. Thus, RTI prescribing guidelines and other prescribing support systems should help control bacterial resistance in the community. However, their effect on resistance patterns is largely unknown and there is an urgent need for collaborative research in this area. Rapid, cost-effective diagnostic techniques are also required and new antibiotics will continue to have a role in disease management.     

The association between bacteria colonizing the upper respiratory tract and lower respiratory tract infection in young children: a systematic review and meta-analysis

BackgroundBacteria colonizing the upper respiratory tract (URT) of young children play a key role in the pathogenesis of lower respiratory tract infection (LRTI).ObjectivesTo systematically review the literature on the association between bacteria colonizing the URT and LRTI among young children.Data sourcesMEDLINE, Academic Search Premier, Africa-Wide Information and CINAHL, Scopus and Web of Science.Study eligibility criteriaStudies published between 1923 and 2020, investigating URT bacteria from LRTI cases and controls.ParticipantsChildren under 5 years with and without acute LRTI.MethodsThree reviewers independently screened titles, abstracts and full texts. Meta-analysis was done using Mantel–Haenszel fixed- or random-effects models.ResultsMost eligible studies (41/50) tested nasopharyngeal specimens when investigating URT bacteria. Most studies were of cross-sectional design (44/50). Twenty-four studies were performed in children in lower- or lower-middle-income countries (LMICs). There was higher prevalence of Haemophilus influenzae (pooled OR 1.60; 95% CI 1.23–2.07) and Klebsiella spp. (pooled OR 2.04; 95% CI 1.17–3.55) from URT specimens of cases versus controls. We observed a positive association between the detection of Streptococcus pneumoniae from URT specimens and LRTI after excluding studies where there was more antibiotic treatment prior to sampling in cases vs. controls (pooled OR 1.41; 95% CI 1.04–1.90). High density colonization with S. pneumoniae (>6.9 log¹⁰ copies/mL) was associated with an increased risk for LRTI. The associations between both Streptococcus and Haemophilus URT detection and LRTI were supported, at genus level, by 16S rRNA sequencing. Evidence for the role of Moraxella catarrhalis and Staphylococcus aureus was inconclusive.ConclusionsDetection of H. influenzae or Klebsiella spp. in the URT was associated with LRTI, while evidence for association with S. pneumoniae was less conclusive. Longitudinal studies assessing URT microbial communities, together with environmental and host factors are needed to better understand pathogenesis of childhood LRTI.     

Reducing uncertainty in managing respiratory tract infections in primary care

Respiratory tract infections (RTIs) remain the commonest reason for acute consultations in primary care in resource-rich countries. Their spectrum and severity has changed from the time that antibiotics were discovered, largely from improvements in the socioeconomic determinants of health as well as vaccination. The benefits from antibiotic treatment for common RTIs have been shown to be largely overstated. Nevertheless, serious infections do occur. Currently, no clinical features or diagnostic test, alone or in combination, adequately determine diagnosis, aetiology, prognosis, or response to treatment. This narrative review focuses on emerging evidence aimed at helping clinicians reduce and manage uncertainty in treating RTIs. Consultation rate and prescribing rate trends are described, evidence of increasing rates of complications are discussed, and studies and the association with antibiotic prescribing are examined. Methods of improving diagnosis and identifying those patients who are at increased risk of complications from RTIs, using clinical scoring systems, biomarkers, and point of care tests are also discussed. The evidence for alternative management options for RTIs are summarised and the methods for changing public and clinicians'' beliefs about antibiotics, including ways in which we can improve clinician–patient communication skills for management of RTIs, are described.