Azithromycin treatment failure in macrolide-resistant Mycoplasma pneumoniae pneumonia

To, Kelvin Kai-Wang; Chan, Kwok‐Hung; Fung, Y.-F.; Yuen, Kwok‐Yung; Ho, Pak-Leung

doi:10.1183/09031936.00041910

Cited by 16 publications

(14 citation statements)

References 11 publications

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“…This is consistent with previous studies showing the inferiority of macrolides in patients with this mutant genotype (8,10). The detection of this mutant phenotype would be especially important for patients who have more-severe clinical presentations (14).…”

Section: Discussionsupporting

confidence: 81%

“…School outbreaks due to MRMP have also occurred (12,13). Treatment failures with macrolides due to pneumonia caused by MRMP have been reported (14). These developments highlight the need for a timely diagnosis of MRMP for the clinical management of patients, infection control, and public health purposes.…”

mentioning

confidence: 99%

“…An important advantage of genotypic testing is that it can be performed directly on the clinical specimens. The techniques that have been applied for the direct detection of MRMP include PCR followed by Sanger sequencing (11,14,16), pyrosequencing (17,18), high-resolution melting curve analysis (19)(20)(21), allele-specific PCR (22), and PCRrestriction fragment length polymorphism (23). In the context of viral infections, natural occurrences of mixed drug-sensitive and -resistant subpopulations are well documented (24)(25)(26)(27)(28).…”

mentioning

confidence: 99%

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Comparison of Pyrosequencing, Sanger Sequencing, and Melting Curve Analysis for Detection of Low-Frequency Macrolide-Resistant Mycoplasma pneumoniae Quasispecies in Respiratory Specimens

Chan

et al. 2013

J Clin Microbiol

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Macrolide-resistant Mycoplasma pneumoniae (MRMP) is emerging worldwide and has been associated with treatment failure. In this study, we used pyrosequencing to detect low-frequency MRMP quasispecies in respiratory specimens, and we compared the findings with those obtained by Sanger sequencing and SimpleProbe PCR coupled with a melting curve analysis (SimpleProbe PCR). Sanger sequencing, SimpleProbe PCR, and pyrosequencing were successfully performed for 96.7% (88/91), 96.7% (88/91), and 93.4% (85/91) of the M. pneumoniae-positive specimens, respectively. The A-to-G transition at position 2063 was the only mutation identified. Pyrosequencing identified A2063G MRMP quasispecies populations in 78.8% (67/88) of the specimens. Only 38.8% (26/67) of these specimens with the A2063G quasispecies detected by pyrosequencing were found to be A2063G quasispecies by Sanger sequencing or SimpleProbe PCR. The specimens that could be detected by SimpleProbe PCR and Sanger sequencing had higher frequencies of MRMP quasispecies (51% to 100%) than those that could not be detected by those two methods (1% to 44%). SimpleProbe PCR correctly categorized all specimens that were identified as wild type or mutant by Sanger sequencing. The clinical characteristics of the patients were not significantly different when they were grouped by the presence or absence of MRMP quasispecies, while patients with MRMP identified by Sanger sequencing more often required a switch from macrolides to an alternative M. pneumoniae-targeted therapy. The clinical significance of mutant quasispecies should be investigated further with larger patient populations and with specimens obtained before and after macrolide therapy.

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Section: Discussionsupporting

confidence: 81%

mentioning

confidence: 99%

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confidence: 99%

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Comparison of Pyrosequencing, Sanger Sequencing, and Melting Curve Analysis for Detection of Low-Frequency Macrolide-Resistant Mycoplasma pneumoniae Quasispecies in Respiratory Specimens

Chan

et al. 2013

J Clin Microbiol

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“…NPA specimens have several advantages over bronchoscopic specimens. First, NPA is a technically simple procedure and therefore feasible even in busy clinical settings (15,16). Second, since NPA specimens are often collected upon admission in patients with upper or lower respiratory tract infections, the use of NPA specimens for diagnosis of PCP can potentially minimize the delay compared to when bronchoscopic specimens are used.…”

mentioning

confidence: 99%

Use of Nasopharyngeal Aspirate for Diagnosis of Pneumocystis Pneumonia

Wong

et al. 2013

J Clin Microbiol

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Quantitative PCR on nasopharyngeal aspirate (NPA) can achieve high sensitivity and specificity in diagnosing Pneumocystis pneumonia (PCP) compared to microscopic examination of bronchoscopic specimens in a population with low HIV prevalence. Since NPA is a minimally invasive procedure, it is ideal as a screening test for PCP. C urrently, microbiological confirmation of Pneumocystis pneumonia (PCP) requires the identification of Pneumocystis cysts or trophozoites using microscopy. Bronchoscopic specimens are preferred because Pneumocystis resides mainly in the alveolar space (1). However, both transbronchoscopic bronchoalveolar lavage and sputum induction pose significant risk to the patient (2-4). Upper respiratory tract specimens are not recommended because of low sensitivity when traditional microscopic examination is used (5). PCR has higher sensitivity than microscopic examination in the detection of Pneumocystis (6) and may overcome the problem of low sensitivity associated with microscopic examination of upper respiratory tract specimens. In this study, we sought to determine whether nasopharyngeal aspirate (NPA) specimens could be used for the diagnosis of PCP.Patients of the Hong Kong West Cluster Hospitals with bronchoscopic specimens (bronchoalveolar lavage fluid [BALF] or bronchial aspirate) submitted to our laboratory for Pneumocystis examination from 1 January 2010 to 31 March 2012 were identified using the laboratory information system. In our laboratory, Pneumocystis cysts were visualized with methenamine silver stain by using standard procedures (7). With this method, Pneumocystis trophozoites or sporozoites could not be detected. Archived NPA specimens from these patients collected during the same hospitalization were retrieved. Only the earliest NPA specimen was tested if multiple specimens were available from the same patient. NPA specimens were collected as described previously (8). Clinical and laboratory data were obtained using the clinical management system. Patients without archived NPA specimens were excluded. A patient was considered to have definite PCP if Pneumocystis was identified in the bronchoscopic specimen by microscopic examination (9). This study has been approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster.DNA was extracted from 200 l of NPA specimens and from other fungi using the QIAamp DNA kit (Qiagen, Hilden, Germany) and DNeasy plant minikit (Qiagen, Hilden, Germany), respectively, according to the manufacturer's instructions (10). Real-time quantitative PCR (qPCR) targeting a 124-bp fragment of the mitochondrial large subunit rRNA (mt LSU rRNA) gene of Pneumocystis jirovecii was performed as described previously (11). Plasmid suspensions were used as standards for quantification and positive controls (Fig. 1).We verified the positive results from the mitochondrial (mt) large-subunit (LSU) rRNA qPCR (LSU-qPCR) by a conventional PCR targeting the mitochondrial small-subunit rRNA (mt SSU rRNA) gene of P. jiro...

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“…Although a previous report emphasized that in vitro resistance to macrolides does not necessarily equate to clinical failure, the presence of MRMP in patients with CAP may result in treatment failure (2)(3)(4)6). Treatment failure in pediatric patients with MRMP infection is evidenced by a febrile period and persistent cough of longer duration than that observed in children infected with macrolide-susceptible M. pneumonia (MSMP) (1, 7).…”

Section: Discussionmentioning

confidence: 94%

Community-acquired Pneumonia Caused by Macrolide-resistant <i>Mycoplasma pneumoniae</i> in Adults

et al. 2014

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We herein describe a case of community-acquired pneumonia caused by macrolide-resistant Mycoplasma pneumoniae (MRMP) in an adult who responded poorly to macrolide antibiotics, progressively deteriorated to acute respiratory failure and then responded effectively to a fluoroquinolone. In a series of 14 patients with M. pneumoniae pneumonia, 11 were infected with MRMP. In seven of the eight cases of MRMP initially treated with macrolides, the patients did not improve, and a marked improvement was observed only after the antibiotic regimen was modified to include fluoroquinolones or tetracyclines. Nationwide surveillance should provide important information regarding the prevalence and empirical treatment of MRMP infection in adults.

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Azithromycin treatment failure in macrolide-resistant Mycoplasma pneumoniae pneumonia

Cited by 16 publications

References 11 publications

Comparison of Pyrosequencing, Sanger Sequencing, and Melting Curve Analysis for Detection of Low-Frequency Macrolide-Resistant Mycoplasma pneumoniae Quasispecies in Respiratory Specimens

Comparison of Pyrosequencing, Sanger Sequencing, and Melting Curve Analysis for Detection of Low-Frequency Macrolide-Resistant Mycoplasma pneumoniae Quasispecies in Respiratory Specimens

Use of Nasopharyngeal Aspirate for Diagnosis of Pneumocystis Pneumonia

Community-acquired Pneumonia Caused by Macrolide-resistant <i>Mycoplasma pneumoniae</i> in Adults

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