Campylobacter coli Empyema Resistant to Macrolides and Fluoroquinolones: A Case Report and Literature Review

Abstract

A 58-year-old man presented with dyspnea and easy fatigability for two months and was diagnosed with empyema. Despite the initial treatment with intravenous ampicillin-sulbactam and chest tube drainage, the patient's condition did not improve. On day 12, Campylobacter coli resistant to both macrolides and fluoroquinolones was identified in the pleural fluid. Meropenem, the only effective antibiotic, was initiated and surgical pleural debridement was performed, thus leading to a clinical recovery. Although 11 cases of empyema caused by Campylobacter spp. have been reported, this is the first case of empyema caused by C. coli that is resistant to both macrolides and fluoroquinolones.

Introduction

Campylobacter is a Gram-negative bacterium that is associated with gastroenteritis and enterocolitis in humans worldwide. Campylobacter coli and Campylobacter jejuni are commonly found in poultry (1). Although C. jejuni has rarely been reported as a cause of empyema (2), no cases of empyema caused by C. coli have yet been documented. Macrolides are first-line antibiotics with fluoroquinolones and tetracyclines as alternatives (1). However, antimicrobial resistance in Campylobacter species has become a growing concern, with some cases showing a poor response to conventional antimicrobial therapy (1). To our knowledge, this is the first reported case of empyema caused by C. coli that was resistant to both macrolides and fluoroquinolones.

Case presentation

A 58-year-old man experienced exertional dyspnea and easy fatigability for two months. His medical history included hypertension, smoking (40 cigarettes per day for 40 years), alcohol abuse, and poor dental hygiene. Three days prior to admission, the patient experienced weakness after alcohol consumption. On the day of admission, the patient felt faint while walking, and was admitted to the emergency department of another hospital. He had a fever, and radiographic imaging revealed left-sided pleural effusion. The patient was subsequently transferred to our hospital.

Upon admission, his vital signs revealed a fever of 38.5°C, tachycardia with a heart rate of 100 bpm, and oxygen saturation of 94% on room air. Physical examination revealed decreased breath sounds in the left lung. Laboratory findings revealed leukocytosis (16,100 /μL with 84.2% neutrophils), an elevated C-reactive protein (CRP) level of 27.64 mg/dL, and a hemoglobin A1c level of 6.5% (Table 1). Chest radiography revealed large right-sided pleural effusion, and chest computed tomography revealed right pleural effusion with pleural thickening (Fig. 1). A pleural effusion specimen obtained by thoracentesis had a milky gross appearance with 89% neutrophils and 7.5% lymphocytes. The pleural fluid also showed elevated protein and lactate dehydrogenase levels (2,304 U/L) and a low pH of 6.883.

Table 1.

The Laboratory Findings of the Patient.

Hematology			Biochemistry			Pleural fluid
Hb	15.5	g/dL	Na	136	mmol/L	TP	4.54	g/dL
Ht	44.2	%	K	3.4	mmol/L	LDH	2,304	IU/L
RBC	476×104	/µL	Cl	98	mmol/L	Glu	4	mg/dL
WBC	16,100	/µL	BUN	10.1	mg/dL	ADA	44	IU/L
Seg	84.2	%	Cr	0.78	mg/dL	pH	6.883
Eo	0	%	TP	6.7	g/dL	Cell fractionations
Baso	0.1	%	Alb	2.9	g/dL	Neutrophils	89	%
Mono	8.8	%	T-bil	0.78	mg/dL	Lymphocytes	7.5	%
Lymph	6.9	%	AST	17	IU/L	Eosinophils	0	%
Plt	21.6×104	/µL	ALT	13	IU/L	Macrophages	3.5	%
PT-INR	1.01		LDH	159	IU/L
APTT	29	s	CK	62	IU/L
			Glu	140	mg/dL
			CRP	27.64	mg/dL
			HbA1c	6.5	%

Figure 1.

(A) Chest X-ray showing large right-sided pleural effusion, (B) and chest CT revealing left pleural effusion with pleural thickening. CT: computed tomography

He was diagnosed with a pleural infection based on neutrophil predominance in the pleural effusion and treated with intravenous ampicillin/sulbactam (3.0 g every 8 h) along with chest tube drainage. Following both a clinical improvement and a reduction of pleural effusion through drainage, the chest tube was removed on the 8th day of admission. However, low-grade fever recurred, and inflammatory markers, including leukocytosis and elevated CRP levels, showed a slight increase after tube removal. Subsequently, a Gram-negative spirochete bacterium, suspected to be Campylobacter, was cultured from the pleural fluid obtained prior to treatment initiation, and no other organisms were isolated (Fig. 2). Blood cultures obtained at the time of admission were negative. Given the typical susceptibility profile of Campylobacter spp., the antibiotic regimen was switched to fluoroquinolones and macrolides on the 13th day of admission. However, inflammatory markers such as the white blood cell counts and CRP levels began to increase again. A Gram-negative Spirochete bacterium was identified as C. coli, showing resistance to both macrolides and fluoroquinolones, and susceptibility only to meropenem (Table 2). Stool cultures performed two weeks after the initiation of antimicrobial therapy were negative. Based on the susceptibility results, the patient's treatment was switched to intravenous meropenem (1.0 g every 8 h) on the 15th day after admission, which resulted in a gradual decrease in inflammatory markers. However, the fever and elevated CRP levels persisted, and lung re-expansion was not achieved owing to residual pleural effusion. Thoracic surgery for pleural debridement was performed on the 29th day of admission. The intraoperative findings revealed encapsulated pleural effusion, pleural thickening, and white parietal pleura consistent with empyema. Postoperatively, a 2-week course of antibiotics was administered and the patient was discharged. No signs of recurrence have been observed since discharge.

Figure 2.

A Gram-negative spirochete bacterium, cultured from the pleural fluid and identified as Campylobacter coli

Table 2.

Antimicrobial Susceptibility Results for Campylobacter coli.

Antibiotics	Antimicrobial susceptibility
Meropenem	Susceptible
Tazobactam/Piperacillin	Resistant
Tetracycline	Resistant
Ciprofloxacin	Resistant

Written informed consent was obtained from the patient for the publication of this case.

Discussion

This is a rare case report of a pleural infection caused by C. coli resistant to both macrolides and fluoroquinolones, thus presenting a treatment challenge owing to antimicrobial resistance. Given that fever and pleural effusion persisted and inflammatory markers remained elevated, prolonged administration of meropenem was considered necessary. Therefore, surgical intervention was performed, thus resulting in symptom resolution and a reduction in the duration of antibiotic therapy. To the best of our knowledge, pleuritis caused by C. coli has not yet been reported previously. Campylobacter spp. have demanding growth requirements, and isolating the organism through culture may be challenging (3). In this case, the organism was successfully identified by mass spectrometry. The antibiotic-resistant nature of this organism complicates treatment, further highlighting the rarity and clinical significance of this case.

Pleuritis with empyema caused by Campylobacter spp. has been reported to be associated with C. rectus and C. curvus. However, these organisms are part of the normal oral flora and they can cause the development of empyema through aspiration (3,4). This mechanism is similar to that of the more common causative pathogens responsible for empyema, and cases of polymicrobial infections have been reported (5). In contrast, C. jejuni and C. coli are primarily associated with enteritis, and reports of pleuritis caused by these species are rare (6). We found two previously reported cases of empyema caused by C. jejuni. In one case, the infection was attributed to the aspiration of undercooked chicken, whereas the route of infection remained unclear in the other case (2,7). Although C. jejuni and C. coli are not typically considered part of the normal human flora, asymptomatic carriage of Campylobacter spp. has been reported in humans (6). In the present case, there was no clear history of enteritis, and the stool cultures were negative. However, it is notable that the stool culture was performed 2 weeks after the initiation of antimicrobial therapy rather than before treatment, which may have affected the results. A preceding episode of asymptomatic or mildly symptomatic Campylobacter enteritis cannot be ruled out. Therefore, the route of infection in this case remains unclear. Furthermore, although the C. coli detected in this case exhibited resistance to multiple antibiotics, the patient had no history of antibiotic use. Antibiotic-resistant C. coli can be acquired from an external source.

In recent years, antibiotic resistance in Campylobacter spp. has been reported in Campylobacter spp., with ciprofloxacin resistance rates ranging from 30% to 70% (1). Therefore, cases involving multidrug-resistant Campylobacter spp., such as the present case, are likely to become more common in the future. Empyema typically requires prolonged antibiotic treatment (5), thus raising concerns regarding further development of antibiotic resistance. In this case, after antimicrobial resistance was identified, treatment was switched to meropenem, which was the only drug to which the organism was susceptible. However, because adequate drainage, an important part of empyema management, was thought to be insufficient, prolonged antibiotic therapy was expected. Therefore, surgical drainage was performed to help improve the condition and reduce the overall duration of antibiotic treatment. In such cases, especially when prolonged antibiotic therapy is anticipated owing to residual pleural effusion, aggressive surgical intervention may achieve an earlier clinical improvement and help mitigate the risk of further antimicrobial resistance. Although empyema caused by Campylobacter spp. is rare, vigilance is warranted given the potential for developing resistance. Accordingly, we reviewed the clinical characteristics and treatment strategies of Campylobacter empyema.

We collected 10 previously reported cases of pleural infections caused by Campylobacter spp. through a PubMed search using the keywords' Campylobacter empyema” and “Campylobacter pleural effusion” (Table 3) (2-4,8-13). The cases included C. rectus in seven cases, C. jejuni in two cases, C. fetus in one case, and C. curvus in one case; no cases involving C. coli were found. Additionally, three cases involved co-infection with other pathogens. Although most patients survive, only one fatal case has been reported. Three cases of antimicrobial resistance, including resistance to levofloxacin, have been reported. However, no previous reports have described multidrug-resistant strains, as was observed in the present case. The surgical management of empyema was performed in this case only.

Table 3.

11 Previous Cases and Our Case of Pleural Infections Caused by Campylobacter Species.

Case	Reference	Age/Sex	Campylobacter species	Co-infection	Treatment	Duration	Drug Resistance	Outcome
1	(8)	24, F	C. rectus	Staphylococcus aureus, Peptococcus asaccharolyticus, Bacteroides pneumosintes	Methicillin, Gentamicin	40 days	Penicillin	Survival
2	(2)	72, M	C. jejuni	-	AMPC/CVA	21 days	Non	Survival
3	(7)	73, F	C. jejuni	-	Ceftriaxone, Pazufloxacin, Minocycline	55 days	-	Survival
4	(9)	24, M	C. fetus	-	Ceftriaxone, Meropenem	40 days	-	Survival
5	(10)	75, M	C. rectus	-	ABPC/SBT, Levofloxacin	55 days	Non	Survival
6	(3)	65, F	C. curvus	Peptostreptococcus spp.	ABPC/SBT, Clindamycin	35 days	-	Survival
7	(11)	69, M	C. rectus	Actinomyces meyeri	Amoxicillin + Amikacin	1 day	Clindamycin	Death
8	(12)	65, M	C. rectus	-	TAZ/PIPC, AMPC/CVA	28 days	-	Survival
9	(13)	71, M	C. rectus	-	ABPC/SBT	24 days	Levofloxacin	Survival
10	(4)	37, F	C. rectus	-	TAZ/PIPC, Clindamycin	over 42 days	Non	Survival
11	Our case	58, M	C. coli	-	ABPC/SBT, Azithromycin + Levofloxacin, Meropenem	43 days	Susceptible only to Meropenem	Survival

AMPC/CVA: amoxicillin/clavulanic acid, ABPC/SBT: ampicillin/sulbactam, TAZ/PIPC: tazobactam/piperacillin

One limitation associated with this case report is that, as mentioned above, the route of infection remains unclear, partly because stool cultures were not performed before the initiation of treatment.

To our knowledge, this is the first reported case of empyema caused by C. coli that exhibited resistance to multiple antibiotics. Although Campylobacter spp. typically cause enteritis, they can also lead to pleuritis in rare instances. Given the increasing incidence of antimicrobial resistance, clinical vigilance is therefore required.

The authors state that they have no Conflict of Interest (COI).