Biomarkers in lower respiratory tract infections

This review aims to provide physicians with an overview of the potential of biomarkers to complement existing clinical severity scores and in conjunction with clinical parameters to improve the diagnosis, risk-stratification and management of lower respiratory tract infections (LRTIs).The usefulness of biomarkers for diagnosing LRTIs is still unclear. However, the specificity of pneumonia diagnosis is high when high sensitivity C-reactive protein (CRP) and procalcitonin (PCT) are used.PCT, CRP and particularly pro-atrial natriuretic peptide (MR-proANP), pro-vasopressin (CT-proAVP) and proadrenomedullin (proADM) levels can reliably predict LRTIs mortality. These markers do not significantly improve the severity scores predictive values, confirming that biomarkers are meant to complement, rather than supersede, clinician’s judgment and validated severity scores.Biomarkers, and particularly PCT, are useful tools as antibiotic treatment duration indicators both in pneumonia and exacerbations of chronic obstructive pulmonary disease (COPD).Even if more data are required to fully appreciate the role of biomarkers in LRTIs management, there is emerging evidence that biomarkers have the potential to improve the daily clinical management of LRTIs.     

Mixed community-acquired lower respiratory tract infections

Although mixed infections are known to be clinically relevant in conditions such as nosocomial pneumonia and ventilator-related pneumonia, it is increasingly recognized that a substantial number of community-acquired lower respiratory tract infections may also be attributed to more than one pathogenic organism. A better definition of the true incidence of mixed infections in community-acquired lower respiratory tract infections is partly derived from recent advances in available diagnostic methods (eg, molecular biology). Two points still must be determined: whether the presence of a mixed infection is associated with altered outcomes and whether empirical antibiotic selection should be modified to account for potential polymicrobial infections.     

De-escalation in lower respiratory tract infections

PURPOSE OF REVIEW: The present article reviews recent data on the de-escalation of empirical antibiotic treatment on pneumonia, with special attention to newer strategies aimed at increasing adequacy and minimizing resistance emergence risks in ventilator-associated pneumonia. RECENT FINDINGS: A de-escalation strategy is feasible in a large proportion of patients with pneumonia, and at least two reports have associated de-escalation with a significantly better survival. Combined with other strategies, such as using biomarkers (e.g. C-reactive protein or procalcitonin), antibiotic heterogeneity, adherence to local microbiological flora, objective clinical criteria of non-response and of clinical ventilator-associated pneumonia resolution, they contribute to rationalizing and individualizing antimicrobial therapy. SUMMARY: A patient-based approach with prompt adequate empirical therapy, using broad-spectrum antibiotics based on reliable local microbiological data with streamlining as soon as microbiological data become available, allow outcomes to be improved and the emergence of resistance to be minimized.     

Antibody treatment of lower respiratory tract infections

Antibody treatment of lower respiratory infection has a long history of success and is receiving renewed interest. A variety of polyclonal and monoclonal preparations are clinically available. Although used primarily for infection prophylaxis, these agents have limited applications in the treatment of established infections. Immune serum was the first effective treatment for pneumococcal pneumonia. Although long-supplanted by the advent of antibiotics, passive immunotherapy for pneumococcal and other infections is being revisited in an era of increasing antibiotic resistance and growing numbers of immunocompromised individuals. Limited clinical evidence supports the use of immune globulins in the treatment of pertussis and severe streptococcal infection. Bone marrow transplant recipients with lower respiratory infections caused by cytomegalovirus or respiratory syncytial virus also may benefit by adjunctive treatment with immune globulins. Additional indications for antibody treatment of respiratory infection may develop with further investigation.     

Randomized comparison of aztreonam and cefuroxime in gram-negative upper urinary tract infections

Summary In order to evaluate the efficacy and safety of aztreonam in hospitalized patients with upper urinary tract infections (UTI), a comparative clinical study with cefuroxime was performed. 62/60% (aztreonam/cefuroxime) of the patients had a complicating factor, mostly obstructive uropathy. I.v. bolus injections were used at a dose of 1 g aztreonam or 1.5 g cefuroxime t.i.d., for a mean of 8.2 days (range: five to 14 days) except in patients with bacteraemia, who received a mean of 10.3 days (range: seven to 13 days) of therapy. 89% of the patients treated with aztreonam and 87% of those who received cefuroxime showed clinical cure and the bacteriological cure rate at one week post-therapy was 70% and 73% in the respective groups. The relapse/reinfection rate was high with both drugs; bacteriological cure at one month post-therapy was only 43% after aztreonam and 40% after cefuroxime. This suggests that these infections may need longer treatment times. Superinfections, mostly asymptomatic urinary colonization, occurred in 7% and 3%, respectively, and adverse reactions in 23% and 12%, respectively, of the patients treated with aztreonam or cefuroxime, the majority being mild and reversible and only 3% and 3%, respectively, requiring discontinuation of the therapy. The t 1/2 for aztreonam following a 1 g i.v. bolus was 2.0 h in six patients with creatinine clearance above 80 ml/min and 3.0 h in seven patients with creatinine clearance between 35–75 ml/min.

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Randomisierte Vergleichsstudie mit Aztreonam und Cefuroxim bei Infektionen der oberen Harnwege durch gramnegative Bakterien

Zusammenfassung Zur Bewertung der Wirksamkeit und Sicherheit von Aztreonam bei stationären Patienten mit Infektionen der oberen Harnwege wurde eine klinische Vergleichsstudie mit Cefuroxim durchgeführt. Ein komplizierender Faktor, meist eine Harnwegsobstruktion, lag bei 62% der mit Aztreonam und 60% der mit Cefuroxim behandelten Patienten vor. Aztreonam wurde in einer Dosis von 1 g und Cefuroxim in einer Dosis von 1,5 g dreimal täglich als i.v. Bolus injiziert. Die mittlere Therapiedauer betrug 8,2 Tage (Bereich fünf bis 14 Tage); Patienten mit Bakteriämie wurden im Mittel 10,3 Tage (Bereich sieben bis 13 Tage) lang behandelt. Die klinische Heilungsrate betrug bei den mit Aztreonam behandelten Patienten 89%, in der Cefuroxim-Gruppe 87%. Bakteriologische Befunde, die eine Woche nach Therapieende erhoben wurden, zeigten in den entsprechenden Gruppen Erregereradikationsraten von 70 bzw. 73%. Die Rate an Rezidiven oder Reinfektionen war mit beiden Medikamenten hoch. Einen Monat nach Therapieende war die bakteriologische Heilungsrate in der mit Aztreonam behandelten Gruppe auf 43% und in der Cefuroxim-Gruppe auf 40% zurückgegangen. Daraus ist zu schließen, daß bei diesen Infektionen eine längere Therapiedauer erforderlich ist. Superinfektionen, bei denen es sich meist um eine asymptomatische Besiedelung der Harnwege handelte, traten nach Aztreonamtherapie in 7%, nach Cefuroxim in 3% der Fälle auf; zu unerwünschten Nebenwirkungen war es unter Aztreonam in 23% und unter Cefuroxim in 12% der Fälle gekommen. In den meisten Fällen waren die Nebenwirkungen leicht und reversibel, ein Abbruch der Therapie war in 3% bzw. 3% der Fälle nötig. Die Bestimmung der Aztreonam-Halbwertzeit ergab bei sechs Patienten mit einer Kreatinin-Clearance von mehr als 80 ml/min nach einer i.v. Bolusinjektion von 1 g 2,0 h, bei sieben Patienten mit einer Kreatinin-Clearance zwischen 35 und 75 ml/min betrug die Halbwertzeit t 1/2 3,0 h.

     

Viral lower respiratory tract infections in Filipino children

Viral causes of acute lower respiratory tract infection were studied prospectively between 15 June and 31 October 1984 in 312 Filipino children less than 5 years old living in periurban slums and middle-class housing. The cause was based on viral antigen detection, virus isolation, and antibody assays. There were 131 children (41.2%) who were admitted to the hospital, and 150 (47%) had an infiltrate on chest radiograph. A total of 198 viral infections were confirmed in 162 patients (51.9%), 42.3% with single viral infection and 9.6% with mixed (two or more) infection. The infections were measles (21.4%), influenza A (15.9%), parainfluenza types 1, 2, and 3 (8.8%), respiratory syncytial virus (7.1%), influenza B (5.8%), enteroviruses (5.1%), adenoviruses (3.9%), herpes simplex virus (1.6%), and cytomegalovirus (1.3%). Viral infections other than measles were seen in 39.7% of the cases. The presence of viral infection correlated with better nutritional status. Influenza A or B diagnosis was associated with mild forms of acute respiratory tract infection, measles and a preceding rash with severe disease.     

Treatment of community-acquired lower respiratory tract infections during pregnancy

The incidence of lower respiratory tract infection (LRTI) in women of child-bearing age is approximately 64 per 1000 population. The spectrum of illness ranges from acute bronchitis, which is very common, through influenza virus infection and exacerbations of underlying lung disease, to pneumonia, which, fortunately is uncommon (<1.5% LRTI), but can be severe. Acute bronchitis is generally mild, self-limiting and usually does not require antibacterial therapy. Influenza virus infection in pregnant women has been recently related to increased hospitalization for acute cardiorespiratory conditions. At present, the safety of the newer neuraminidase inhibitors for the treatment of influenza virus infection has not been established in pregnancy and they are not routinely recommended. In influenza virus infection complicated by pneumonia, antibacterial agents active against Staphylococcus aureus and Streptococcus pneumoniae superinfection should be used. There are few data on infective complications of asthma or COPD in pregnancy. The latter is rare, as patients with COPD are usually male and aged over 45 years. Management is the same as for nonpregnant patients. The incidence and mortality of pneumonia in pregnancy is similar to that in nonpregnant patients. Infants born to pregnant patients with pneumonia have been found to be born earlier and weigh less than controls. Risk factors for the development of pneumonia include anemia, asthma and use of antepartum corticosteroids and tocolytic agents. Based on the few available studies, the main pathogens causing pneumonia are S. pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae and viruses. Beta-Lactam and macrolide antibiotics therefore remain the antibiotics of choice in terms of both pathogen coverage and safety in pregnancy. In HIV-infected pregnant patients, recurrent bacterial pneumonia, but not Pneumocystis carinii pneumonia (PCP), is more common than in nonpregnant patients. Trimethoprim/sulfamethoxazole (cotrimoxazole) has not definitely been associated with adverse clinical outcomes despite theoretical risks. Currently it is still the treatment of choice in PCP, where mortality remains high. In conclusion, there are few data specifically related to pregnant women with different types of LRTI. Where data are available, no significant differences compared with nonpregnant patients have been identified. In considering the use of any therapeutic agent or investigation in pregnant patients with LRTI, safety aspects must be carefully weighed against potential benefit. Otherwise, management strategies should not differ from those for nonpregnant patients. Further research in this area is warranted.     

Trends in bacterial pathogens of lower respiratory tract infections

OBJECTIVES: This study was conducted to determine the bacterial aetiology of lower respiratory tract infections in this environment as well as update the clinicians in the various antimicrobial alternatives available in the treatment. METHODS: Between September 2002 and February 2005, 157 bacterial pathogens from 556 patients with lower respiratory tract infections were isolated from sputum specimens, and subjected to susceptibility testing, using standard bacteriologic techniques. RESULTS: Out of the 556 cases, only 150 (27%) had an established bacterial aetiology. One pathogen was demonstrated in 143 (95.3%) patients and seven (4.7%) had mixed infections. The most prevalent single pathogen was Klebsiella pneumoniae (38%) while the most prevalent bacterial combination was Klebsiella and Pseudomonas species (2%). Isolates of Klebsiella pneumoniae were susceptible to ciprofloxacin, gentamicin and ceftriaxone. CONCLUSIONS: Bacteriological diagnosis and antibiotic resistance surveillance are indispensable in the effective management of lower respiratory tract infections.     

Impact of lower respiratory tract infections on health status

Acute exacerbations of COPD have a broad range of effects on the patients in addition to cough and sputum production. These include malaise, increased dyspnea, diminished tolerance and social restriction. No single clinical or physiological measure captures this multiplicity of effects adequately. Health status measurement using instruments erroneously termed ;quality of life' questionnaires can provide this integrative function. Validation studies have shown that these scores reflect exercise capacity, respiratory symptoms, disability in daily life, and impaired mood. Furthermore they relate to levels of arterial hypoxaemia in COPD and blood leucocyte count in patients with bronchiectasis. Health status scores have been shown to predict hospital readmission or death in patients with COPD. Recent studies have shown that whilst sputum color and volume recover within a week of starting treatment, full recovery of health status may take over three months. This is consistent with the observation that exacerbation frequency is strongly related to health status and a recent report that the rate of decline in health status over time is related to the frequency of exacerbations. Health status instruments were developed originally to measure treatment efficacy, but they also provide insights into acute exacerbations of COPD and their clinical importance.     

Respiratory picornavirus infections in Korean children with lower respiratory tract infections

Recently, human rhinoviruses (RVs) and enteroviruses have been suggested as important etiological agents in young children with lower respiratory tract infections (LRTIs). We investigated the role of respiratory picornaviruses in hospitalized children with LRTI. A total of 233 nasopharyngeal samples were collected from hospitalized children with LRTIs from July 2004 to January 2006. All specimens were tested for the presence of human respiratory syncytial virus (hRSV), influenza virus A, influenza B, parainfluenzavirus, and adenovirus using direct immunofluorescent assay, and for human metapneumovirus (HMPV) by RT-PCR. Detection of RV was performed in nasopharyngeal samples by a RT-PCR assay that incorporated a BglI restriction enzyme digestion of the picornavirus RT-PCR amplicon, and detection of enterovirus was accomplished by hemi-nested RT-PCR using specific primers. Viral agents were detected in 70.4% (164/233) of the study population. The most frequently detected viruses were RV (64/233, 27.4%), hRSV (48/233, 20.6%), and enterovirus (43/233, 18.4%). Picornaviruses were detected as the sole viral agents in 27.0% (63/233) of children, whereas mixed viral infection was detected in 12.0%. These results suggest that picronavirus infection is an important etiological cause of LRTIs in Korean children.     

鲇鱼爱德华杆菌下呼吸道感染47例分析

目的　探讨鲇鱼爱德华杆菌致下呼吸道感染的危险因素和治疗，及该菌近年检出之原因。方法　统计１９５９ ～１９９８ 年住院患者鲇鱼爱德华杆菌痰培养阳性率，并对其作临床分析。结果１９９６ 年以前人工方法检测１７ ５００ 份标本，检出率为０ ％ ，１９９７ 、１９９８ 年用仪器检测１９６２ 份标本，检出率为２３ ％ 。两种方法检出率经卡方检验，χ２ ＝ ４２０２３ ， Ｐ＜ ０００１ 。该菌对亚胺硫霉素，头孢噻甲肟，妥布霉素等抗生素有极高敏感度。结论　鲇鱼爱德华杆菌是院内下呼吸道感染的少见条件致病菌，机体抵抗力下降是导致该菌感染的危险因素，检测技术的改进是发现此菌的主要原因