Doxycycline or moxifloxacin for the management of community-acquired pneumonia in the UK?

Macrolide monotherapy is currently recommended as first-line treatment of mild-to-moderate community-acquired pneumonia (CAP) in penicillin-intolerant/allergic individuals in the UK. However, resistance rates among the commonest cause, Streptococcus pneumoniae, now exceed 10% in the UK and a review of alternative agents is therefore timely. This review considers the relative merits of two agents, doxycycline and moxifloxacin, which are candidates to replace macrolides for second-line therapy of non-severe CAP.

Non-fermentative Gram-negative bacteria.

Over the past decade, non-fermenting Gram-negative bacteria have emerged as important opportunistic pathogens in the increasing population of patients who are immunocompromised by their disease or medical treatment. These bacteria are assisted by their ubiquitous distribution in the environment and have a propensity for multiple, intrinsic or acquired drug resistance. The infections that they cause now pose significant problems in terms of treatment and infection control, whilst the commonly observed rapid emergence of bacterial resistance to new antimicrobial compounds raises concerns regarding the clinical lifespan of these agents. Studies are urgently required to assess whether combination therapy can improve the long-term utility of new drugs in the treatment of patients infected with non-fermenters.

Invasive fungal infections: a review of epidemiology and management options.

Fungi are increasingly recognised as major pathogens in critically ill patients. Candida spp. and Cryptococcus spp. are the yeasts most frequently isolated in clinical practice. The most frequent filamentous fungi (moulds) isolated are Aspergillus spp., but Fusarium spp., Scedosporium spp., Penicillium spp., and Zygomycetes are increasingly seen. Several reasons have been proposed for the increase in invasive fungal infections, including the use of antineoplastic and immunosuppressive agents, broad-spectrum antibiotics, and prosthetic devices and grafts, and more aggressive surgery. Patients with burns, neutropenia, HIV infection and pancreatitis are also predisposed to fungal infection. The epidemiology and clinical features of fungal infections are reviewed, together with antifungal agents currently or soon to be available.

A pseudo-outbreak of respiratory infection with Acinetobacter species.

We describe an apparent outbreak of respiratory infection with Acinetobacter species involving 14 patients over 8 days. Epidemiological investigation revealed two consecutive pseudo-outbreaks of infection caused by two consecutive, unrelated laboratory errors in the processing of sputum, nasopharyngeal, and endotracheal aspirates.

Ribotyping of coagulase-negative staphylococci.

The discriminative capacity of ribotyping was initially assessed without knowledge of results obtained for the same isolates by use of more established typing methods. Forty-eight isolates of coagulase-negative staphylococci (CNS) from peritoneal fluids were studied. They were collected prospectively during 31 consecutive episodes of infection associated with peritoneal dialysis in 17 patients. DNA was digested by the restriction endonucleases EcoRI or HindIII and ribotyped by means of a biotinylated cDNA probe to 16S + 23S staphylococcal ribosomal RNA gene sequences. These methods in combination produced a total of 27 types which compared well with numbers of groups distinguished by other typing methods: limited biotype-antibiotic resistogram (ARB; 28), antibiotic resistogram alone (25), API-Staph (12), phage typing (9) and plasmid analysis (22). Ribotyping was highly reproducible and typed all isolates, including those that were not phage-typable (35) or did not contain plasmids (4). When used in a hierarchical manner with ARB, ribotyping results produced 13 additional types in comparison with the other three methods. When used hierarchically with all other typing systems, a further five types were found among isolates from two patients. However, some of the differences observed as a result of ribotyping could have been due to subtle changes produced by mutation, lysogenisation or gene transposition. Since the method requires additional time, expense and technical expertise, it is likely to be useful only when answers to specific epidemiological problems are required or as an initial screen before using other methods of genetic analysis.

The evaluation of a typing scheme for coagulase-negative staphylococci suitable for epidemiological studies.

A typing scheme was devised for an epidemiological study of infection with coagulase-negative staphylococci in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The scheme was constructed in four stages suitable for the screening of large numbers of isolates: antibiogram, biotype, phage type, and plasmid profile. The discrimination and reproducibility of the scheme was established by the examination of 50 isolates from 33 consecutive episodes of peritonitis affecting 18 patients. The discrimination of the scheme was 76%, with a reproducibility of 86%. Indistinguishable strains occurred in individual patients only, demonstrating that no cross-infection between patients occurred during the 10-month period of collection of strains, and suggesting that the discriminating power of the scheme was, in fact, much higher. The antibiogram, selected as the first stage of the scheme because it was the simplest and cheapest test, proved to be the most discriminatory stage, providing 60% of the final discriminatory power.

Detection by PCR and analysis of the distribution of a fibronectin-binding protein gene (fbn) among staphylococcal isolates.

The fibronectin-binding proteins of Staphylococcus aureus are considered to be important virulence factors for colonisation and infection. The polymerase chain reaction (PCR) was used to detect part of a gene equivalent to the fbnA gene of S. aureus in 120 isolates of staphylococci (S. aureus, S. epidermidis, S. haemolyticus, S. simulans, S. hominis, S. warneri, S. cohnii and S. lugdunensis). Primers specific for the binding domain region of the fbnA gene of S. aureus produced PCR products of the predicted sizes (93 and 207 bp). The identity of the PCR products was confirmed by digestion with DdeI and nucleic acid hybridisation. The fibronectin-binding activity of the staphylococci was determined with a particle agglutination assay (PAA). The fbn gene was found to be present by PCR in 107 of the 120 staphylococci tested, irrespective of their site of isolation, and expression of the gene was detected by PAA in 101 of the 120 strains.

Anaerobic periurethral flora of healthy women and women susceptible to urinary-tract infection.

The anaerobic periurethral microbial flora of 25 healthy women was compared with that of 29 women attending the urinary-tract-infection clinic at the Royal Free Hospital. The latter group consisted of 19 patients receiving long-term prophylactic antimicrobial therapy and 10 with proven recurrent urinary-tract infection not receiving prophylactic treatment. The numbers and species of anaerobes isolated from each group were similar. Lactobacillus spp. were the most frequently isolated organisms in each group and the most numerous. Bacteroides spp. were the next most frequently isolated. In any one subject, the anaerobic flora varied considerably during the study period of approximately 6 months. Thus, the anaerobic flora is not affected by recurrent urinary-tract infection in the past nor by the use of prophylactic chemotherapy. It does not appear to exert a protective role against the initiation of urinary-tract infection.

The epidemiology of peritonitis caused by coagulase-negative staphylococci in continuous ambulatory peritoneal dialysis.

The epidemiology of 10 episodes of CAPD peritonitis caused by coagulase-negative staphylococci was studied. The infecting micro-organism was found in prospective skin swabs in six episodes, widely distributed and as the predominant, or equally predominant, organism at each site but was not detected in swabs taken more than 12 weeks before the episode of peritonitis; this suggests recent acquisition. Infecting strains were no more likely to be adherent or to produce slime than non-infecting strains, nor had they any other characteristic detected in our typing scheme that might lead to their detection before peritonitis developed.

Real-time PCR investigation into the importance of Fusobacterium necrophorum as a cause of acute pharyngitis in general practice.

Fusobacterium necrophorum is recognized as the cause of a severe life-threatening illness characterized by bacteraemia with metastatic abscesses following an acute sore throat (Lemierre's disease). However, the importance of F. necrophorum as a cause of simple sore throat in the community is unknown. Using quantitative real-time PCR with primers targeting the rpoB gene, 100 routine throat swabs collected from patients presenting to general practitioners with pharyngitis were analysed for the presence of F. necrophorum-specific DNA. The results were compared with those obtained from throat swabs collected from 100 healthy subjects. Ten clinical samples were positive for F. necrophorum DNA, identified as F. necrophorum subspecies funduliforme, using a haemagglutinin-related protein gene-specific PCR assay. All the healthy controls were negative (two-tailed P value = 0.0015; Fisher exact test). These findings suggest that F. necrophorum may play a more important role as a cause of simple sore throat in the community than has been previously appreciated.

Infectious consequences of continuous ambulatory peritoneal dialysis.

The peritoneal cavity of patients undergoing CAPD is critically immunocompromised and infectious peritonitis is the most important complication of the technique. Nevertheless, recent research into the epidemiology and pathogenesis of infections caused by the most important microorganisms has enabled significant reductions in peritonitis rates to be made. Peritonitis caused by Staphylococcus aureus and Pseudomonas aeruginosa can be prevented by eliminating their principal source, an infected Tenckhoff catheter wound. The source of infection for coagulase-negative staphylococci and other pseudomonads cannot be eliminated, but peritonitis caused by these organisms may be prevented by interrupting their routes of entry into the peritoneal cavity. The identification of host factors predictive of enhanced susceptibility to infectious peritonitis offers the further possibility of prevention by immunological approaches. Although the main difficulties surrounding the diagnosis of infective peritonitis have been clarified, approximately 20% of episodes remain culture-negative, with multifactorial aetiology. Initial (empirical) combination antibiotic therapy can be both appropriate and effective in approximately 85% of cases. Intraperitoneal monotherapy with fluoroquinolones has been equally successful, and these agents may prove effective by the oral route, offering considerable advantages in cost and convenience. Approximately 5% of episodes of bacterial peritonitis are unresponsive to antibiotic therapy. These cases may be conveniently managed by the technique of Tenckhoff catheter removal and replacement at a single operation.

A comparison of four culture methods for diagnosing infection in continuous ambulatory peritoneal dialysis.

Dialysate effluent from 41 patients presenting with 54 episodes of CAPD peritonitis was examined by four culture techniques, three employing methods for the lysis of peritoneal leucocytes. The most efficient method employed a distilled water lysis-centrifugation technique (81% of episodes culture-positive). Filtration (without leucocyte lysis) was less effective (74% culture-positive). The results of a mechanical leucocyte lysis technique were less satisfactory still, the culture positive rate of 74% being compromised by the recovery of the infecting organism in low numbers, and by an association with a high incidence of plate contamination. The results of a bile-salt lysis technique were the least satisfactory (67% culture-positive).

The prevention of infection with Staphylococcus aureus in continuous ambulatory peritoneal dialysis.

We describe the control of wound infection with Staphylococcus aureus in patients undergoing continuous ambulatory peritoneal dialysis at St. Thomas' Hospital. Forty-nine percent of 61 catheters inserted in 1985 and 1986 became infected, and the majority of these infections were acquired in hospital. Infection was impossible to eradicate and was frequently associated with the subsequent development of S. aureus peritonitis, which was the most important cause of catheter loss. Strict adherence to aseptic techniques for catheter insertion and care, combined with eradication of S. aureus carriage, reduced the infection rate to 12% for the 50 catheters inserted in 1987, abolished hospital-acquired infection and reduced the S. aureus peritonitis rate tenfold, without the use of prophylactic antibiotics. S. aureus infection is a serious but avoidable complication of continuous ambulatory peritoneal dialysis.

Infective complications associated with the use of the Quinton 'Permcath' for long-term central vascular access in haemodialysis.

The major complication of central venous catheterization for immediate access for haemodialysis is infection. The Quinton Permcath is a tunnelled, double lumen, flexible silastic catheter with a Dacron cuff, and is claimed to be associated with a low rate of infection. In a two-year study we have monitored all complications including catheter-associated infection related to this device in haemodialysis patients while following a simple aseptic programme for the care of the catheter exit wound. Thirty four Permcaths were inserted in 30 patients for a mean duration of 6.2 months (SD +/- 5.7; range 2 days to 23 months). Catheter use amounted to a total of 197 months. Of twenty-seven catheter wound infections, 6 (22%) were caused by Staphylococcus aureus, and 15 (56%) by coagulase-negative staphylococci or corynebacteria. These occurred in 19 patients, giving an exit site infection rate of one episode per 7.4 catheter months. Catheter-associated septicaemia occurred in three patients (two S. aureus, one S. epidermidis), at a rate of one episode per 66 months. It was possible to correlate three episodes of infection with breakdown in aseptic care. This study confirms the low rate of infection associated with the use of the Permcath, and we conclude that the design of the device and aseptic care of the catheter and its wound contribute to this.

Mycobacterium tuberculosis as a cause of peritonitis in a patient undergoing continuous ambulatory peritoneal dialysis.

Tuberculous peritonitis is reported in an Asian immigrant undergoing continuous ambulatory peritoneal dialysis (CAPD). Unusual laboratory findings which resulted in delayed diagnosis are described.

Q fever in pregnancy.

We describe a case of acute symptomatic infection with Coxiella burnetii acquired between the 16th and 28th week of pregnancy. Oral ciprofloxacin therapy was started on diagnosis, at the 28th week of pregnancy, but symptoms were unabated after 3 weeks treatment, suggesting persisting infection of the products of conception. Caesarean section was therefore performed at 32 weeks gestation when a healthy infant was delivered, and subsequent investigations showed no evidence of transplacental spread of infection. Infection control measures were applied at the time of delivery to minimize the risk of infection to obstetricians and midwives from potentially infectious products of conception.

Active intervention dramatically reduces CAPD-associated infection.

In 1987 a preventive programme was initiated to address the problem of high hospital and community-acquired CAPD infection. It concentrated on reducing Staphylococcus aureus carriage, improving aseptic operative technique, intensive training for nursing staff and patients in stringent aseptic care of the exit site, and avoidance of contact of the exit site with unsterile water. This programme was associated with an overall 10-fold reduction in exit site infection, a 2-fold reduction in peritonitis, and a 4.5-fold reduction in catheter loss from infection. These reductions have been sustained. Preventing infection in CAPD patients requires persistence and commitment but improves the patient's quality of life and reduces the cost of treatment.

Real-time TaqMan PCR for rapid detection of genes encoding five types of non-metallo- (class A and D) carbapenemases in Enterobacteriaceae.

A real-time TaqMan multiplex polymerase chain reaction (PCR) assay was developed to detect genes encoding five types of serine carbapenemases (GES, IMI/NMC, KPC, OXA-48 and SME). The assay was validated using control strains known to produce each of these types of enzyme and was then further assessed by 'blindly' testing 59 previously characterised clinical isolates, including 19 with serine (KPC or OXA-48) carbapenemases, 22 with metallo- (IMP, VIM or NDM) carbapenemases, and 18 with carbapenem resistance contingent upon extended-spectrum ß-lactamase (ESBL) or AmpC production combined with porin loss. The assay detected and correctly assigned the serine carbapenemases in all five positive control strains and in 19 clinical isolates. No false-positive results were seen for isolates with metallo-enzymes or for those that lacked a carbapenemase. The five serine carbapenemase genotypes could also be distinguished by melt-curve analysis or the molecular size of the amplicons.