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[Three cases of lower respiratory tract infection worsened after rhinovirus infection].

We experienced three cases of lower respiratory tract infections worsened after Rhinovirus infection. Case 1: A 42-year-old male with diffuse panbronchiolitis was admitted to our hospital with the complaint of dyspnea on November 21, 1988. Rhinovirus was isolated from nasal washing and P. aeruginosa was cultured from transtracheal aspiration (TTA). Case 2: A 67-year-old male, whose underlying disease was pulmonary asbestosis, was admitted to our hospital complaining of pyrexia on June 12, 1990. Rhinovirus was isolated from TTA and H. influenzae and others were cultured from TTA. Case 3: A 64-year-old male with pulmonary emphysema was admitted to our hospital with a complaint of dyspnea on August 11, 1989. On December 17, 1989 the patient developed rhinorrhea and complained of purulent sputum, pyrexia and dyspnea after five days. Rhinovirus was isolated from nasal washing and TTA and S. nonhaemolyticus and others were cultured from TTA. As indicated in this report, it is interesting to study the relationship between viral infection of the upper respiratory tract and bacterial infection of the lower respiratory tract.

Adult

Azithromycin in lower respiratory tract infections.

Azithromycin is a new azalide antimicrobial agent which has a broad spectrum of activity against common lower respiratory tract pathogens including pneumococci, staphylococci, Legionella species, Mycoplasma and Chlamydia species. In particular, it is more active against Haemophilus influenzae than other macrolides. In comparison to other new macrolides, azithromycin achieves higher tissue and intracellular concentrations and these concentrations are sustained for several days after dosing due to a long elimination half-life. The efficacy of azithromycin against lower respiratory tract infections has been proven in several clinical studies. Once-daily dosing with azithromycin, over a 3- or 5- day period was as effective as a 10-day course of other commonly used antibiotics such as amoxycillin/clavulanic acid, erythromycin or cefaclor in lower respiratory tract infections. Azithromycin short-course therapy may offer an advantage in terms of patient compliance and the duration of treatment.

Animals

Lower respiratory tract infections after abdominal operations: epidemiology and risk factors.

OBJECTIVE: To find out the incidence and aetiology of lower respiratory tract infections after abdominal operations and identify predisposing factors. DESIGN: Prospective open study. SETTING: Department of General Surgery, Hospital Germans Trias i Pujol, Barcelona, Spain. SUBJECTS: 2,083 patients having abdominal operations between March 1985 and June 1987 excluding splenectomies, and those requiring thoracoabdominal incisions. MAIN OUTCOME MEASURES: The presence of three or more of the following: temperature of 38 degrees C or more, cough with mucopurulent sputum, raised white cell count, or changes on the chest radiograph or bronchogram. RESULTS: 50 patients (2.4%) developed lower respiratory tract infections. Micro-organisms were isolated from 15 (30%), the most common being Haemophilus influenzae. The most important risk factors were American Society of Anesthesiologist's grade, duration of anaesthesia, age, and operations on the upper gastrointestinal tract. CONCLUSION: Further work is needed to investigate other possible predisposing factors and develop a predictive score.

Abdomen

Comparative study on the use of co-trimoxazole and tetracycline in the treatment of lower respiratory tract infections.

A double-blind trial was carried out on 116 patients with lower respiratory tract infection and systemic manifestations. One group received co-trimoxazole (480 mg. trimethoprim and 2,400 mg. sulphamethoxazole daily), and the other group received 2 g. tetracycline daily. The trial, as judged by clinical improvements, the reduction of purulent sputum and the rate of eradication of infection, showed a better result with co-trimoxazole. The incidence of side-effects were higher in the group receiving tetracycline compared with those receiving co-trimoxazole.

Drug Combinations

Activation of alveolar macrophages after lower respiratory tract infection.

Alveolar macrophage function has been studied in relation to bacterial infection of the lower respiratory tract. First, LRT macrophages were examined after exposure of rabbits to Listeria monocytogenes aerosols. Macrophages obtained from the LRT of animals 10 to 48 days after infection were activated, as evidenced by greater adherence to culture dishes and increased ability to ingest and kill both the original infecting organism and unrelated organisms, when compared to normal alveolar macrophages. Next, the in vitro effects on normal alveolar macrophages of incubation supernatants of control and antigen-stimulated lymphocytes (LRT and lymph node) from animals infected with L. monocytogenes or Streptococcus pneumoniae were evaluated. As manifested by increased adherence and phagocytosis, and an enhanced nonspecific bactericidal activity, alveolar macrophages were activated by the antigen-stimulated supernatants. These stimulated lymphocyte supernatants contain lymphokines (MIF), but the exact nature of the alveolar macrophage activating factor(s) remains to be determined. These observations, together with recent evidence that alveolar macrophages respond to lymphokines (MIF), suggest that the effector mechanism for cell-mediated immunity in the LRT is intact.

Aerosols

Clinical experience with cefadroxil in upper and lower respiratory tract infections.

Cefadroxil is a new semisynthetic oral cephalosporin with a broad spectrum of activity against both Gram-positive and Gram-negative organisms. Absorption of cefadroxil is unaffected by food, its serum levels are prolonged and it is excreted in the urine at a relatively slow rate compared to cephalexin. In the treatment of 108 patient with upper or lower respiratory tract infections, cefadroxil effected 93% complete cures. Fifty-five of the patients had upper respiratory tract infections and fifty-three had lower respiratory tract infections; among them cefadroxil acheived clinical success rates of 100% and 96%, respectively. Cefadroxil was clinically successful in eight (89%) out of nine patients whose infections were caused by mixed aetiologies. The principal causative agents were Staphylococcus aureus, beta-haemolytic streptococci, Streptococcus pneumoniae and Klebsiella pneumoniae. Overall bacterial eradication produced by cefadroxil was 112 (91%) of 123 organisms isolated from 108 patients. Reports of mild and transient side-effects in only 3.7% of the patients showed that the drug was well tolerated.

Adolescent

Comparative trial of co-trimoxazole and tetracycline in the treatment of lower respiratory tract infection.

One hundred and twenty-six adult patients with acute lower respiratory infection were studied in a double-blind trial. One group was treated with co-trimoxazole (480 mg trimethoprim and 2400 mg sulphamethoxazole) per day and the other group with tetracycline 2 g per day. The results showed that co-trimoxazole was significantly more effective than tetracycline as judged by clinical improvement, and the reduction in sputum volume and purulence. No haematological abnormalities were observed, but the incidence of side-effects, though mostly mild, was higher in the group of patients on tetracycline than in the co-trimoxazole group. The results of this study strongly suggest that co-trimoxazole may be a useful and reliable drug in the treatment and control of acute lower respiratory tract infection in the developing countries.

Adolescent

Steady-state pharmacokinetics of rufloxacin in elderly patients with lower respiratory tract infections.

The pharmacokinetics of rufloxacin, after repeated doses, was evaluated in 12 elderly patients with lower respiratory tract infections. Patients were given a single loading dose of 400 mg on the first day of treatment and single daily maintenance doses of 200 mg for the next 6-9 days. Serum concentrations of the drug were determined by high-performance liquid chromatography (HPLC) at regular intervals during treatment and fitted to a one-compartment open model for repeated doses. The maximum serum concentration after the first dose was 6.46 +/- 1.06 (mean +/- SEM) micrograms/ml and was reached in 4.3 +/- 0.8 h after the first administration. The elimination half-life was 28.7 +/- 4.1 h. The area under the serum levels-time curve from 0 to 24 h was 103 +/- 14 micrograms/h/ml after the first dose. On the last day of observation it increased to 155 +/- 28 micrograms/h/ml, with a mean extent of accumulation of 2.3 +/- 0.3 times. The elimination half-life was comparable to those in other studies in healthy young subjects, while plasma levels were about 80% higher. These results suggest that in elderly patients elevated drug concentrations may be reached in the serum. Although no untoward reactions related either to the drug concentration in serum or the dose have been noted with rufloxacin, this patient population should nevertheless be monitored carefully for adverse effects.

Aged

Pharmacokinetics of rufloxacin once daily in patients with lower respiratory tract infections.

The pharmacokinetic properties of rufloxacin, a new quinolone antibacterial agent, were evaluated in ten patients with lower respiratory tract infections. Patients were given 400 mg of rufloxacin once a day for seven to nine days. Plasma concentrations of the drug were determined by high-performance liquid chromatography and bioassay at regular intervals during treatment. After the first administration, maximal plasma concentrations were 3.17 +/- 0.36 mg/l (mean +/- SEM) and were reached at 4.2 +/- 0.7 h. At the end of treatment peak plasma concentrations increased to 7.26 +/- 0.52 mg/l. Elimination half-life was 38.2 +/- 2.9 h, with a mean extent of accumulation of 2.96 +/- 0.30. Treatment was well tolerated, with no abnormalities noted during routine laboratory examinations. Two days after the last administration, measurable levels of rufloxacin were still observed in plasma, indicating that the long half-life of rufloxacin assures valuable antibacterial activity even after discontinuation of treatment.

Administration, Oral

[Follow-up study of the effect of acute lower respiratory tract infection during childhood on chronic bronchitis in adults].

In order to study the relationship between the acute lower respiratory tract infection (ALRTI) during childhood and the occurrence of chronic bronchitis in adults, 90 cases (infection group) admitted to hospital for ALRTI before 7 yr old were followed up 24-31 years later. Their siblings without ALRTI during childhood were selected as the control group. The prevalence of chronic bronchitis in the infection group (12.2%) is significantly higher than that of the control group (2.2%). It is concluded that ALRTI during childhood may play an important role in the occurrence of chronic bronchitis in adults. Further analysis showed that infection and smoking have synergic effects on the occurrence of chronic bronchitis.

Adult

Safety and efficacy of temafloxacin versus ciprofloxacin in lower respiratory tract infections: a randomized, double-blind trial.

Temafloxacin, a new fluoroquinolone with broad-spectrum anti-bacterial activity and a favourable pharmacokinetic profile, was evaluated in a prospective, randomized double-blind multicentre study in which 564 patients were enrolled. Ambulatory adults with lower respiratory tract infections were randomly assigned to receive temafloxacin 600 mg or ciprofloxacin 750 mg, each given every 12 h for 7-14 days. Cure or improvement occurred in 93.8% of temafloxacin patients and 93.1% of ciprofloxacin recipients (P greater than 0.05). Bacteriological eradication rates were higher in the temafloxacin group than in the ciprofloxacin group (99.5% vs 92.5%; P = 0.001) primarily because of the failure of ciprofloxacin to eradicate Streptococcus pneumoniae (P = 0.01). Both regimens were well tolerated. In patients who received concomitant theophylline, gastrointestinal and central nervous system disturbances occurred in a higher percentage of patients in the ciprofloxacin group than the temafloxacin group (36.4% vs 9.4%; P less than 0.05). This study indicates that temafloxacin would be suitable for the empirical treatment of lower respiratory tract infections, including high-risk groups such as the elderly and heavy smokers.

Adolescent

Performance evaluation of a commercial multiplex pathogen panel for detection of bacteria in sputum specimens from non-ICU patients with suspected lower respiratory tract infection.

Rapid diagnostic testing can improve pathogen detection and lead to targeted antibiotics. The BioFire FilmArray Pneumonia Panel (BFPP) is a multiplex PCR that has displayed strong concordance with traditional microbiologic techniques. However, most existing literature focuses on deep respiratory specimens, and there is sparse literature on performance in sputum specimens. This retrospective, single-center study included adult patients between 1 September 2022 and 31 August 2024 who had collection of a BFPP with standard of care (SOC) culture from a sputum specimen on a non-intensive care unit (ICU) floor or in the emergency department if admitted to a non-ICU floor. Out of 189 BFPPs performed on 189 sputum specimens, a total of 141 bacterial targets were detected. Between the BFPP and SOC culture, the overall positive percent agreement and negative percent agreement (NPA) were 96.3% and 54.9%, respectively. The positive predictive value (PPV) was 26.3% while the negative predictive value was 98.9%. Patients with greater than 24 h of antibiotic exposure prior to BFPP collection had a lower PPV compared to patients with less than 24 h or no exposure (13.6% vs 29.6% vs 30.4%). The lowest concordance was observed for Haemophilus influenzae (15.4%), Moraxella catarrhalis (18.2%), Streptococcus pneumoniae (19%), and Staphylococcus aureus (22.7%), several of which are fastidious in culture. BFPP showed a high NPA, with all bacterial targets having an NPA greater than 90%, except H. influenzae (82%). Based on these data, a negative BFPP in sputum specimens could help to rule out a bacterial pneumonia, but the benefit of a positive test remains unclear.IMPORTANCEThis study evaluates the BioFire FilmArray Pneumonia Panel (BFPP) by comparing its performance to standard of care cultures exclusively in sputum specimens from non-intensive care unit patients with suspected lower respiratory tract infection. Findings show an overall high positive percent agreement and negative predictive value but a low negative percent agreement and positive predictive value, suggesting that a negative test in sputum specimens could be beneficial when attempting to rule out a bacterial infection, but the benefit of a positive test remains unclear, particularly if common airway colonizing bacteria are detected and at low semi-quantitative thresholds. Clinical symptoms should guide test interpretation in patients with positive BFPP results but negative culture growth.

Humans

Antimicrobial resistance among agents of hospital-acquired lower respiratory tract infection in the UK and Ireland: trends from 2008/2009 to 2018/2019.

OBJECTIVES: To survey trends in antimicrobial resistance among the pathogens of hospital-acquired lower respiratory tract infection (HA-LRTI), which causes significant mortality and morbidity, particularly among ventilated patients. METHODS: The BSAC Surveillance collected quotas of major HA-LRTI pathogens from sentinel sites from 2008/09 (October to September) to 2018/19. MIC testing was by BSAC agar dilution. Resistance mechanisms were inferred from synergy tests, interpretive reading and PCR. RESULTS: Target numbers of Staphylococcus aureus, Pseudomonas aeruginosa and Enterobacterales-dominated by Escherichia coli and Klebsiella spp.-were reliably collected. Acinetobacter spp. collections were small, reflecting low incidence. Resistance rates fell or fluctuated, with no major rises. Notable declines included: (i) a fall in the proportion of MRSA among S. aureus from c. 40% to 10%; (ii) a halving, since 2012/13, in 'triple-resistance' to carbapenems, aminoglycosides and fluoroquinolones among Acinetobacter baumannii sensu stricto, from c. 24% to 9%; (iii) reductions in AmpC-associated cephalosporin resistance among Enterobacter cloacae and Serratia isolates, and (iv) falls in fluoroquinolone resistance among Enterobacterales, except Klebsiella pneumoniae. Resistance rates in P. aeruginosa remained low, though higher than in bacteraemia. Cephalosporin resistance in E. coli and K. pneumoniae was largely ESBL associated and, unlike AmpC-associated resistance in Enterobacter and Serratia spp., did not decline notably. Except for OXA-23 in A. baumannii, carbapenemases remained extremely rare. Antistaphylococcal oxazolidinones, tigecycline, ceftolozane/tazobactam, ceftazidime/avibactam and ceftobiprole retained uneroded activity. CONCLUSIONS: From 2008/09 to 2018/19, there were no major rises in resistance among the principal agents of HA-LRTI; for several important organisms/resistance combinations there were notable declines.

Humans

AIDS patients with bacterial lower respiratory tract infections: treatment with ofloxacin versus sulbactam-ampicillin.

In this open-label, randomized, parallel-groups study the Authors compare the parenteral administration of a beta-lactamase inhibitor associated with a semisynthetic penicillin (sulbactam-ampicillin) with the oral administration of a 3rd-generation quinolone (ofloxacin), in 20 HIV-infected subjects suffering from lower respiratory tract (LRT) infections. 12 patients were classified as AIDS, 6 as ARC (AIDS related complex) and 2 as asymptomatic seropositives. The risk of becoming HIV-infected and the work load for the health staff were also evaluated. The clinical and microbiological results indicate that oral ofloxacin is as effective as parenteral sulbactam-ampicillin for the treatment of LRT infections in HIV-positive individuals. In addition, the members of the health staff reported significantly less difficulty in administering ofloxacin in respect to sulbactam-ampicillin.

AIDS-Related Opportunistic Infections

Investigation of associations between the neonatal gut microbiota and severe viral lower respiratory tract infections in the first 2 years of life: a birth cohort study with metagenomics.

BACKGROUND: Early-life gut microbiota affects immune system development, including the lung immune response (gut-lung axis). We aimed to investigate whether gut microbiota composition in neonates in the first week of life is associated with hospital admissions for viral lower respiratory tract infections (vLRTIs). METHODS: The Baby Biome Study (BBS) is a prospective birth cohort, which enrolled mother-baby pairs between Jan 1, 2016, and Dec 31, 2017, at three UK hospitals. In the present study, we only included BBS babies with a sequenced first-week stool sample and successful data linkage. Stool was collected in the first week of life for shotgun-metagenomic sequencing. We examined the following microbiota features: alpha diversity (Chao1, Shannon, and Simpson indices) and community structures (cluster-partitioning against medoids method). The participants were followed up through linkage to the Hospital Episode Statistics-Admitted Patient Care (HES-APC) database to determine vLRTI hospital admission incidence in the first 2 years of life. We used Poisson mixed-effects models for univariable and multivariable analyses to evaluate the association between microbiota features and vLRTI hospital admission incidence, adjusting for confounders identified through direct acyclic graphs. FINDINGS: 3305 (95%) of the 3476 BBS-enrolled babies for whom consent to data linkage was obtained were included in the present study. 1111 (34%) babies had a first-week sequenced stool sample, of whom 1082 (97%; 564 born vaginally and 518 born by caesarean section) were successfully linked to HES-APC, and had median follow-up of 2·0 years (IQR 1·4-2·9). Most babies were born at term (996 [92%] ≥37 weeks gestational age and 1070 [99%] >35 weeks gestational age) and healthy (1050 [97%] had no comorbidities), and 520 (48%) were female and 562 (52%) were male. Higher first-week gut microbiota alpha diversity was associated with reduced rates of vLRTI hospital admission (Chao1 Index adjusted hazard ratio [HR] 0·92 [95% CI 0·85-0·99]; Shannon Index adjusted HR 0·57 [0·33-0·98]; and Simpson Index adjusted HR 0·36 [0·11-1·20]). Three microbiota clusters were identified. Cluster 1 had a mixed composition and cluster 2 was dominated by Bifidobacterium breve, with both clusters observed in babies born vaginally and by caesarean section. Cluster 3 was found only in vaginally born babies and was dominated by Bifidobacterium longum. Having cluster 1 (mixed) or cluster 2 (B breve dominated) was independently associated with increased rates of vLRTI hospital admission compared with cluster 3 (B longum dominated; cluster 1 [mixed] 3·05 [1·25-7·41] and cluster 2 [B breve dominated] 2·80 [1·06-7·44]). INTERPRETATION: We report observational evidence that first-week gut microbiota differences are associated with clinically severe vLRTI in young children. This study identified bacterial species that could be of interest for vLRTI prevention. This finding has important implications for the design of future research and intervention strategies. FUNDING: The Wellcome Trust and Wellcome Sanger Institute core funding.

Humans

Antimicrobial resistance among agents of community-associated lower respiratory tract infection in the UK and Ireland: trends from 1999/2000 to 2018/2019.

OBJECTIVES: The BSAC Respiratory Surveillance Programme examined resistance trends among Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis from patients with community-acquired lower respiratory tract infection (CA-LRTI). METHODS: Quotas of isolates were sought per collecting site from 1999/00 to 2018/19; an annual October start date captured winter infection peaks within single years. MIC testing was by BSAC agar dilution. β-Lactamase detection with nitrocefin and pneumococcal serotyping by classical methods or WGS. RESULTS: Resistances were uncommon, except that β-lactamases occurred in c. 20% of H. influenzae from 2012/13 following earlier rises, and in >90% of M. catarrhalis throughout. Only 0.11% (12/10881) of S. pneumoniae were fully resistant to penicillin; co-amoxiclav inhibited 97.8% of 13526 H. influenzae and >99.9% of 6309 M. catarrhalis isolates. Cefotaxime inhibited >99% of all isolates at breakpoint, as did relevant fluoroquinolones in the fewer years tested. Tetracycline inhibited >98% of H. influenzae and M. catarrhalis and 85% of S. pneumoniae. Significant shifts were: (i) fluctuating resistances to tetracyclines, macrolides and penicillin in pneumococci, reflecting serotype replacements; (ii) expansion, from 2012/13, in the proportion of H. influenzae with β-lactamase-independent amoxicillin/co-amoxiclav resistance; and (iii) increasing high-level amoxicillin resistance (MIC  > 64 mg/L) among β-lactamase-positive H. influenzae. MIC differentials were seen for cephalosporins between β-lactamase-positive and β-lactamase-negative M. catarrhalis, greatest (512-fold) for ceftaroline. CONCLUSIONS: CA-LRTI remains eminently treatable, yet shifts are occurring in the serotypes of S. pneumoniae most associated with resistance and in the nature of amoxicillin resistance in H. influenzae. β-Lactamase-related cephalosporin MIC differentials for M. catarrhalis are striking but their clinical significance remains uncertain.

Humans

Cefuroxime in the treatment of lower respiratory tract infection.

Cefuroxime is a new parenteral antibiotic with a wider spectrum of activity than earlier cephalosporins and is particularly active against Haemophilus influenzae, including strains resistant to ampicillin due to beta-lactamase production. From 18 centres, 274 patients suffering with 275 infections were treated with cefuroxime sodium using the standard regimen of 750 mg 8-hourly by intramuscular injection. The clinical results showed a 90% success rate in the patients with bronchopneumonia (105), 91% in patients with post-operative pneumonia (74), and 89% in the patients with acute exacerbations of chronic bronchitis (96). Renal function was closely monitored during therapy, and no adverse changes attributable to cefuroxime therapy were seen in any patient, including those who also received frusemide. Two patients (0.7%) developed a rash, although 8 penicillin-allergic patients were treated without incident. From these studies, it can be concluded that 750 mg cefuroxime 8-hourly is effective in the treatment of lower respiratory tract infections. It is suggested that the attributes of this antibiotic may offer several advantages over existing therapies.

Adolescent

Complications of severe lower respiratory tract infections in Singapore children.

Over one year period, 240 children with severe lower respiratory infection was admitted to a general paediatric department. The mortality was 1.6%. Apart from pleural effusions and skin exanthems, several major complications were noted. These were septicaemia (1), apnoea (2), encephalopathy (3), meningitis (1), Stevens Johnson Syndrome (1), bronchiectasis (1) and lung abscess (1).

Child